INTRODUCTION

“The human spirit is stronger than anything that can happen to it” – Jack Thorne

Cancer, once a poorly understood illness, has emerged as the target of vigorous scientific inquiry and medical advancements. Any uncontrolled growth of cells that invade and cause adjacent tissue impairment is known as cancer. Oral cancer is the term described as cancers occurring in the mouthparts that include lips, cheeks, sinuses, tongue, hard and soft palate, or the base of the mouth extending up to the oropharynx.¹ Oral Cancer is regarded as one of the most debilitating, devastating, and disfiguring of all cancers. It presents the whole healthcare team with important obligations, challenges, and a real opportunity to save lives. Oral cancer often begins as a small, unfamiliar, unexplained growth or sore within the oral cavity.

Globally, oral cancer ranks 17th among all types of cancer in terms of both incidence and mortality. India has the largest number of oral cancer cases and more than one-third of the total global burden. In India, oral cancer ranks as the second most common cancer, and is the number one cancer among males.² Oral cancer care, therefore, poses a serious health challenge to developing nations undergoing a rapid economic transition. In India, around 130,000 new cases and >75,000 deaths were reported only in the year 2020, with an expected doubling of incidence by 2040 based on accounting of demographic changes. The increasing cases of oral cancer become an important public health concern.

This burden of oral cancer is further complicated by the late-stage diagnosis and low survival rates. In India, about 70% of oral cancer cases are reported in the advanced stages. Because of detection in the late phase, the chances of cure are very low, leaving a five-year survival rate at around 50%. Oral cancer incidence from 1990 to 2005 reveals the benefit of public health interventions, such as screening, demonstrating potential significant reductions in oral cancer incidence. Oral cancer incidence in India has shown a downward trend. However, the reduction is much more dramatic where there is a much higher prevalence of oral cancer. Early detection and treatment, therefore becomes the key to lower mortality rates and better survival rates for oral cancer patients in the country.³

Oral squamous cell carcinoma (OSCC) dominates among all oral cancer cases, which usually originates in the oral cavity with some discernible oral potentially malignant disorders (OPMDs). Tobacco consumption (both smoking and smokeless forms), chewing areca nut products with or without tobacco, excessive alcohol consumption, unhygienic oral condition, and sustained viral infections, including the human papillomavirus (HPV), are some of the chief risk factors for the incidence of oral cancer.⁴ Lack of knowledge, variations in exposure, and behavioral risk factors are responsible for a wide variation in its incidence and outcomes.⁵

In the 1960s, the oral cancer management guidelines focused primarily on surgical approaches and treatment of advanced cases. However, a new direction was taken in the next few decades, which started with the growing recognition of the role of HPV in oropharyngeal cancers. Along with this, the global fleet of health professionals managing oral cancers turned toward more conservative treatment options for certain cases, such as organ-sparing surgeries and radiation therapy (RT).

Guidelines began to address the importance of multidisciplinary care involving surgeons, oncologists, radiologists, and other specialists and ncreased focus on targeted therapies and immunotherapies in advanced cases. However, the real breakthrough happened a decade later when early detection and prevention through routine screenings, especially in high-risk populations became the clarion call of the torchbearing health professionals of oral cancer. Till today, with each new document being published by each health organization is an addition to the herculean task of reducing the mortality and morbidity caused by oral premalignant lesions and oral cancers.

Over time, there were numerous lateral integrations in varied ways, which made the battle against oral cancer a multidisciplinary healthcare approach. From primordial to primary to tertiary prevention, each step became a complex continuum of care and a cross-linked framework, amongst which, the most important was the Alma Ata Declaration approach to place people’s health in people’s hands. Many international organizations initiated awareness campaigns to educate the public about the risk factors, signs, and symptoms of oral cancer. The policy became stronger and advocacy became more challenging. Then came the Phoenix Framework Convention on Tobacco Control (FCTC), the international treaty developed by the World Health Organization (WHO) to address the global health epidemic caused by tobacco consumption and exposure to tobacco smoke. The FCTC is considered one of the most significant international public health treaties and provides a comprehensive framework for tobacco control measures adopted by the World Health Assembly in 2003 and entered into force in 2005. The treaty provides a roadmap for countries to implement evidence-based strategies to combat the tobacco epidemic and harm reduction for population health.

There have been a number of innovative ideas for reducing oral cancer burden, ranging from mobile applications to artificial intelligence and now quantum computing.

The National Academy of Medical Sciences (NAMS), India, understands the mammoth prevalence of oral cancer in the country and this side of the world and plays a crucial role in various aspects of prevention, awareness, research, treatment, and support. The key roles taken up are advocacy and public awareness, education and outreach, support for patients and caregivers, research and innovation, collaboration and partnerships, surveillance, guidelines, and standards. With this policy document, we intend to hammer an effective and efficient nail in the coffin of tobacco burden, morbidity, and mortality of oral cancer. We thus aim to provide each citizen of India with an affordable and accessible preventive and health-promotive care with regard to oral cancer and achieve the highest possible quality of life.

This high burden of oral cancer cases, increased mortality, lack of awareness, and a higher out-of-pocket expenditure (OOPE) in its care calls for a multipronged and multifaceted action. Apart from strengthening therapeutic efforts, increasing preventive efforts in an aggressive manner through research in various diagnostic adjuncts^6,7 and screening programs is also essential for reducing the magnitude of the problem. Despite preventive approaches and the availability of services, the oral cancer burden remains a serious problem at the community level in India. Thus, this white paper, under the auspices of the National Academy of Medical Sciences, discusses the manner in which oral cancer and tobacco use can be tackled better.

METHODOLOGY

The report of the task force provides an insight into oral cancer as a public health problem along with etiology strategies to diagnose, treat, and prevent it while providing recommendations to improve upon the availability and delivery of treatment for oral cancer in India.

As the experts in the task force were from across the country, a virtual mode of conducting the proceedings was mutually agreed upon dates. The task force during the initial meetings developed a consensus on the key themes and subthemes with a focus on the Indian context. Once the themes were identified based on consensus, they were divided and allocated to technical experts. They reviewed the recent evidence along with current reports and data pertaining to various aspects of oral cancer in India on different databases like Pubmed, Scopus, LILACS, and Cochrane using different medical subject headings terms and synonyms for oral cancer. Following this, the sections were revised and compiled through an iterative process of feedback and discussions while generating consensus of individual panel member opinions on critical issues.

The initial working draft was circulated among the task force expert members, and comments were sought. The working draft was modified based on the suggestions. Subsequently, multiple online meetings were held in which the experts deliberated on the various aspects of the document. Further modifications were made to the document based on the final observations and recommendations received from the experts. Finally, the draft was finalized.

SITUATION OF ORAL CANCER IN INDIA

Oral cancer is of significant public health concern in India, as it is one of the most common types of cancer affecting a large population. The predominant risk factor for developing oral cancer is tobacco consumption. The continual use of tobacco in both smoking and smokeless forms is a major contributor to tumor development in the oral cavity in both young as well as the adult Indian population, thereby affecting all age groups.⁵

A gender-based distinction has been made for oral cancer cases, where males show a high incidence of tobacco-related cancer.⁸

In India, epidemiologically, Kerala has the lowest incidence of oral cancer, while West Bengal reports the highest. In the western regions of the country like Maharashtra, the highest occurrence of oral malignancy is reported in the age group of ≥60 years. Another study from Chennai reported that oral cancer is most prevalent at the base of the tongue, which further enhances the chances of metastasis.⁹ Other locations reported are buccal mucosa (BM), alveolus, and the base of the mouth for the occurrence of oral cancer.¹⁰ It is also reported that the nutritional diet is important for oral cancer patients to maintain the oral health-related quality of life.

India is now the world capital for oral cancer cases, as it shares one-third of the global burden. Southern parts of India present the highest incidence rate of oral cancer. Risk factors such as tobacco, alcohol, diet and nutrition, oral thrush, dental problems, chronic irritation from sharp teeth or ill-fitting dentures, and more play an important role in developing cancer, with poor oral health and HPV infection as the two emerging causes.

The financial burden toward the patient is very high during the treatment of oral cancer; most of the patients leave the treatment midway, which further adds to the mortality rate. The treatment of oral malignancy primarily depends on the location and size of the tumor and the feasibility of organ preservation in patients. Screening, early diagnosis, and timely treatment are critical aspects to tackle oral cancer-related burdens in India.⁸

SOCIOCULTURAL AND ECONOMIC ATTRIBUTES OF ORAL CANCER IN INDIA

“Sociocultural factors refer to a wide array of societal and cultural influences that impact thoughts, feelings, behaviors, and ultimately health outcomes. There are several dimensions encompassed by the term, which can include race, ethnicity, ethnic identity, sex, language, beliefs, value systems, attitudes, and religion.” There are other factors included under this domain such as socioeconomic status (SES), age, level of acculturation, occupational issues, family structure and intergenerational issues, religious beliefs, and spirituality. The majority of the studies have reported predominantly on behavioral factors and few on social factors.

Hence a thorough literature review was conducted to explore the reported sociocultural factors in the context of the Indian population. The search yielded 26 articles, and 12 other articles were obtained through manual search referring to the bibliography of other articles conducted in the Indian population and reported elsewhere, which were both analytical and cross-sectional studies.

The literature review revealed limited recognition of the association between social, cultural, and psychological factors and oral cancer despite an abundance of literature on these factors being responsible for inequalities in health. The search also revealed limited descriptive and analytical studies related to oral cancer and associated factors, but the emphasis was more on behavioral factors, with tobacco consumption as the primary factor. Since cross-sectional studies do not give the true picture of association, we have emphasized predominantly the results from analytical studies.

Socioeconomic status: The published work on the relationship between SES and oral cancer has mainly been in the form of cross-sectional studies. From such studies, increased risk of oral cancer appears to be associated with lower SES as compared to a higher class and an inverse association between education level and oral cancer.¹¹ Similar results have been reported with an odds ratio (OR) of 6.5 in South India and an OR of 3.4 in North India.¹² Very few studies have reported on the totality of the SES scale; rather, individual measures were reported.¹³ However, studies from Bhopal¹⁴ and Jharkhand¹⁵ have reported no association between education and oral cancer with an OR of 1.0 at 95% confidence Interval (CI).

Income has also been reported to be associated with lower income and higher chances of oral cancer (OR 2.41), lower occupational class (OR 1.84), and lower education (OR 1.85).¹³ The socioeconomic perspective has been shown to be a potential major risk factor in the etiology of oral cancer by being recognized as the cause of the cause. Low education comes with a lack of awareness, which is confirmed as a risk factor for oral cancer.¹⁶

Age: Oral cancer has traditionally been considered as a disease mainly affecting the older age group, with a substantial portion of people of older ages and a proportion of cases arising between 30 and 40 years. The age-standardized incidence and mortality rates for lip and oral cavity cancer were 9.8 and 5.4, respectively, per 100,000 population in the world scenario, whereas it was 10.3% of new cases in India.¹⁷ The age groups of 41–50 years had the OR of 1.63 and 51–60 years had the OR of 1.79.¹⁸ The age of initiating the habit of tobacco consumption is before the age of 20,¹⁹ with the lowest being reported as 15 years.²⁰

Gender: Oral cancer has been reported to be the most common cancer among males in the Indian subcontinent.²⁰ The incidence of lip and oral cancer among males is 16.2 and for females is 4.6 per 100,000 population.¹⁷ The pooled data from the registries report on new cases amongst males to be 679,421 and females 712,758.²¹ The age-standardized incidence and mortality rates are 14.8 for males and 4.6 for females per 100,000. The odds of developing oral cancer among men was 2.49,¹⁸ whereas when it comes to tobacco consumption in all forms, women were in higher percentage (90%) as compared to men (59%) with OR of 42.4 and 5.1, respectively,¹⁹ though women were reported to start consuming tobacco at an earlier age than men.²²

Geographical location: The central region of India was found to have the highest incidence of oral cancer,²⁰ which includes four states (Rajasthan, Uttar Pradesh, Madhya Pradesh, Chhattisgarh). The largest difference was observed in Central India with OR of 5.0 (3.6–7.0) and South India with OR of 3.8 (2.9–5.1).¹² Oral cancer incidence increases with age, with a typical pattern of cancer of associated sites of oral cavity seen in the northeast region (Cachar district, Kamrup urban, Manipur, Mizoram, Nagaland, Meghalaya, Sikkim, and Tripura). Oral cancer was the highest in the central region among males (64.8%) in the 70–75-year age group, followed by AAR in the northeast and west regions of India (58.4%) in the 60–69-year age group.²⁰ The total tobacco consumption in rural areas of the country is 38.4% compared to urban areas with a smoking prevalence of 25.3%.²³

Cultural factors: Since time immemorial, tobacco and areca nut consumption has been indigenous and socially and culturally acceptable in India. Betel quid chewing has cultural and traditional significance among the Indian population. It is consumed during religious meetings, events, celebrations, and festivals, irrespective of age group, gender, and SES. Betel quid is a mixture of areca nut and slaked lime wrapped within betel leaf to which tobacco, spices, and sugar are added and is optional.²⁴ Areca nut and tobacco consumption have been recognized as a known risk factor for oral leukoplakia, oral submucous fibrosis (OSF), and OSCC. Migration studies have reported on two times and five times the risk for oral cancer mortality for men and women, respectively, than the native English and Welsh.²⁵

Tobacco consumption: Tobacco consumption in all forms has been identified as a key risk factor. Various risk factors discovered in various Indian studies include smokeless tobacco, gutkha, khaini, zarda, bidi, betel quid, mishri, paan, and supari, with a hierarchy of risk with gutkha (OR = 12.8), chewing tobacco (OR = 8.3), supari (OR = 6.6), bidi (OR = 4.1), and mishri (OR = 3.3).²⁶ When compared to control groups, a relatively high percentage of cases (42.9%) had the practice of retaining quid in mouth, and this finding was determined to be highly statistically significant (OR = 18 [CI 5.88; OR 61.65]).²⁷ One of the key predictors of incidence is the average duration between tobacco and tobacco product consumption. Multiple epidemiological studies show that the incidence of oral cancer varies considerably between different parts of the world, with the highest levels in the Indian subcontinent.²⁸

Alcohol consumption: Alcohol consumption is a known risk factor for oral cancer, contributing to 75% of oral cancer in Western countries both individually and when consumed with tobacco.²⁹ Such figures are not available for the Indian population, but alcohol as a risk factor has been reported. At the same time, the possibility of alcohol consumption with OSF with OR 2.1 (95% CI 1.0–4.4) was reported.³⁰ The habit of drinking and consuming tobacco simultaneously increased with age, predominantly among 30–69 years of age group.³¹

As well, alcohol consumption appears to be linked to tobacco use, as drinking increases the odds of smoking and chewing tobacco by two times. According to studies, smoking is a gateway to drinking alcohol, and those who smoke have a much higher risk of doing so than those who don’t. Studies have shown that consumption of both tobacco and alcohol is more addictive and increases the risk of developing oral cancer as compared with tobacco use alone.³²

Smoked tobacco: Bidis and cigarettes are the two popular forms of smoked tobacco, of which bidis are smoked majorly by the poor as the cost is less than fifth of cigarettes. The age adjusted relative risk (RR) for bidi smokers was 1.64 (95% CI 1.47–1.81) and increased risk from 1.42 (95% CI 1.20–1.68) to 1.78 (95% CI 1.57–2.02) with an increasing number of bidis per day.³³

Areca nut: Areca nut has recently been identified as a risk factor for oral cancer, though its beneficial use has been reported in food, medicine, and sociocultural customs.³⁴ Despite limited documentation on its benefits, the principal alkaloid—arecoline—triggers stimulation within the nervous system, providing subjective enhancements like heightened well-being and alertness.³⁵ The meta-RR generated from 13 studies from India summarized an RR estimate of 2.41 (95% CI 1.82–3.19) with a moderate level of heterogeneity (I2 = 65%). When restricted to studies that adjusted for tobacco smoking, the RR for BQ was 2.94 in the Indian subcontinent. Restricting the analysis to nonsmokers, the RR for BQ was 20.21 2.20 in the Indian subcontinent. The RR was much higher in women (RR = 14.5, 95% CI 7.63–27.76) than men in India for the consumption of betel quid.³⁴ The carcinogenicity of betel quid is well established,^36,37 with risk in betel quid chewers without tobacco at 6.6 (3.0–14.8).²⁶

The risk of developing OPMD among betel quid chewers was leukoplakia 4 (2.7–6.1), OSF 47.2 (20.2–110.4), erythroplakia 12.5 (1.6–19.2),³⁶ and OPMD as a whole was 5.5 (1.6–19.2).³⁸

Dietary factors: Fresh fruits and vegetables consumption was more in controls compared to cases.¹¹ The OR for betel quid containing raw tobacco and areca nut was 35.25 with OR of 0.22 for the vegetarian diet.

Sociopolitical factors: There are around 200 million users in India representing about two-thirds of the global smokeless tobacco (SLT) users, with more than 350,000 people dying due to SLT-related diseases. Alarming is the fact that we are the largest producers of tobacco, both in crops and in the form of products.³⁹ The predominant reason being the availability of SLT products in the informal markets (homemade, unregulated, untaxed products) and the brand stretching and brand sharing strategies of the SLT industry.⁴⁰ Since manufacturing bidi is a small-scale cottage industry and home-based activity, close to ten million people are employed from the vulnerable and underprivileged groups, which has the risk of exposing the employees to tobacco during the manufacturing process. Most of the SLT products are made for single use, thus making them inexpensive and challenging for tax administration.^33,41,42

Other factors: The role of peer influence, role models, family history of tobacco, valuing tobacco as a medicine, traditional acceptance has other sociocultural factors⁴³ and residence, marital status, caste, religion, and material deprivations have been reported as major social determinants of tobacco use.^44,45 There are several studies which shows the influence of sedentary lifestyle, family history of cancer on delayed seeking consultation. Fear of treatment, lack of access to quality healthcare, and time constraints were other major factors reported.⁴² These factors have been established through cross-sectional studies; hence, scope for further analytical studies is needed to support this literature.

In conclusion, our present report offers an overview on the risk factors and oral cancer among the Indian population, with tobacco consumption emerging as a major risk factor, and each of the gender being at risk either for initiating the habit early or for manifestation. Aggressive programs aimed at all age groups, genders, and socioeconomic class for prevention of tobacco use and geographic location-specific policy initiatives owing to differing use of tobacco products may be the need of the hour.

A table depicting studies confirming the association of tobacco types and alcohol with oral cancer as per the literature reported from Indian studies is mentioned in Supplementary Material-Annexure 1.

ORAL POTENTIALLY MALIGNANT DISORDERS AND ORAL CANCER

OPMDs consist of a diverse group of conditions with an increased risk of malignancy. The term OPMD was introduced in 2007 following a collaborative meeting led by the WHO Collaborating Centre for Oral Cancer. Recognizing that late-stage oral cancer is linked with a poorer prognosis compared to cases detected in their early stages, considerable emphasis is placed on identifying oral cancer at a nascent stage—ideally prior to invasion—when the abnormality is still an OPMD.

It is important to recognize that a patient diagnosed with any of these OPMDs have an increased risk of developing oral cancer compared to a person with a healthy mucosa. The risk of malignancy in a patient with an OPMD can fluctuate based on multiple factors, and it has been approximated to be between 5 and 100 times higher than the risk in the general population.

Major risk factors for prevalent OPMDs are comprehensively delineated in the literature. These encompass the use of tobacco in both smoked and smokeless forms, excessive alcohol consumption, and the practice of chewing betel quid containing areca nut. While the potential involvement of HPV has been deliberated, its role needs to be further explored. The following entities are included in the 2022 WHO classification of OPMD:

• Erythroplakia

• Erythroleukoplakia

• Leukoplakia

• Proliferative verrucous leukoplakia

• Submucous fibrosis

• Palatal lesions associated with reverse smoking

• Oral lichenoid lesions

• Oral lichen planus

• Smokeless tobacco keratosis

• Oral graft versus host disease

• Lupus erythematosus

• Familial cancer syndromes, including Fanconi anemia, dyskeratosis congenita, xeroderma pigmentosum, Li Fraumeni syndrome, Blooms syndrome, ataxia telangiectasia, and Cowden’s syndrome.⁴⁶

Oral leukoplakia: Leukoplakia is defined as “White plaques of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer”—WHO Collaborating Centre (2007). Oral leukoplakia is recognized as the most prevalent OPMD. The average worldwide occurrence of leukoplakia spans from 1% to 4%; however, notably higher rates are documented in Southeast Asia. While leukoplakia is more frequently observed in males, women face an elevated risk of malignant transformation.

In terms of their clinical presentation, leukoplakias are categorized as either homogeneous or nonhomogeneous. Homogeneous leukoplakia manifests as a primarily white lesion that is uniformly flat and possesses consistent texture. The majority of leukoplakias (90%) exhibit homogeneity. In contrast to nonhomogeneous leukoplakias, these homogeneous forms have a lower likelihood of undergoing malignant transformation. Nonhomogeneous leukoplakia, however, can display a combination of white and red-speckled surface [Figure 1]. This type of leukoplakia might have an irregularly flat, nodular, verrucous, or ulcerated appearance.

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Figure 1:

(A) Clinical presentation of speckled leukoplakia, an appearance of white and red patch (white arrow). (B) H&E stained section (10x) showing high risk dysplasia (black arrows). H&E: Hematoxylin and Eosin.

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Erythroplakia: Erythroplakia is uncommon, with a prevalence of less than 0.1% with a higher malignant transformation rate (MTR) than leukoplakia. Erythroplakia is a thin or slightly depressed red patch of the oral mucosa and is less common than leukoplakia. Erythroplakia is much more likely to be associated with high-grade dysplasia or carcinoma (>90%) in comparison to leukoplakia [Figure 2].

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Figure 2:

(A) Clinical presentation of erythroplakia (white arrow) (B) H&E stained section (4x) showing abrupt transition from normal epithelium to severely dysplastic epithelium (black arrows). H&E: Hematoxylin and Eosin.

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Proliferative verrucous leukoplakia: Hansen et al. (1985)⁴⁷ defined proliferative verrucous leukoplakia (PVL) as leukoplakias that tend to spread and become multifocal. PVL occurs predominantly in elderly women with a mean age of 66.8 years. Gingiva and alveolar ridge are the most frequently involved sites, followed by the BM—tongue. PVL is slow-growing, persistent, and irreversible, and with time areas become exophytic and wart-like. Initial lesions in PVL patients are often indistinguishable from OLP and homogeneous oral leukoplakias, forming smooth to fissured/verruciform or verrucous white or mixed white and red patches, usually without ulceration. Multiple noncontiguous lesions or single lesion >40 mm involving one site or single lesion >30 mm involving contiguous sites are characteristic. Thick, verrucoid marginal gingival leukoplakias encircle the tooth, especially when multifocal is characteristic of PVL.

Histology (Leukoplakia, Erythroplakia, Proliferative Verrucous Leukoplakia): The histopathological evaluation of oral epithelial dysplasia (OED) varies between OPMDs and is considered to be one of the most critical factors in risk assignment and determination of prognosis. OED is a spectrum of architectural and cytological epithelial changes resulting from the accumulation of genetic alterations. OED can be diagnosed on the basis of architectural or cytological features alone.

Traditionally, OED is divided into three grades of severity, and judging the number of thirds affected is one factor in assigning grades. Architectural and cytological atypia usually increases in higher-grade lesions, with mild dysplasia characterized by cytological atypia limited to the basal third, moderate dysplasia by extension to the middle third, and severe dysplasia by extending to the upper third. However, defining dysplasia grade only in this manner oversimplifies the complexity of grading. Cytological atypia confined to the basal third may be sufficient for a diagnosis of severe dysplasia depending on individual features present, particularly bulbous rete processes, budding and disorganization of basal cells, and marked cytological atypia. Similarly, a lesion with a verrucous or papillary surface with only mild atypia may be considered to be a high-risk lesion. Histological features of PVL reflect the clinical appearance as early lesions show keratosis, often without dysplasia. Lichenoid/interface mucositis features may be present in early PVL cases. These gradually develop the typical verrucous morphology. Further progression to corrugated hyperkeratotic to proliferative stage and ultimately to malignancy can be seen.

Corrugated hyperkeratotic lesions exhibit verrucopapillary or disproportionate flat hyper ortho-/parakeratosis with minimal or no dysplasia. Skip areas of normal to abnormal to normal is a common finding. A sharp abrupt transition from adjacent unaffected normal epithelium is usually seen [Figure 3]. Proliferative bulky epithelial lesions demonstrate atypical, hyperkeratotic epithelial architecture with/without dysplasia. Both exophytic and endophytic growth pattern can be present and the epithelium shows bulbous rete pegs that sometimes coalesce. Histopathology alone is not able to provide a risk assessment of the disease. Recent applications of more sensitive risk assessments include assessment of the DNA ploidy status—aneploid lesions indicate a higher risk.

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Figure 3:

(A) Clinical presentation of proliferative verrucous leukoplakia involving multiple sites of oral cavity (white arrow). (B) H&E stained section (4x) showing corrugated parahyperkeratotic lesion, not reactive (black arrows). H&E: Hematoxylin and Eosin.

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Oral submucous fibrosis: OSF is a chronic, insidious disease characterized by progressive fibrosis of submucosal tissues of the oral cavity and the oropharynx with a risk of transformation to squamous cell carcinoma (SCC).” It is common in South Asian countries where the betel quid habit is prevalent. MTR has been found to be 7.6%. Clinical features include a burning mouth, depapillation of the tongue, blanching, and leathery mucosa. Later stages showed the development of fibrous bands.

Early stages showed hyperplastic epithelium to atrophy with loss of rete ridges in later stages. Epithelial dysplasia can be noticed with the progression of the disease. Budding changes in the submucosa at an early stage are minimal, with slightly increased vascularity, inflammatory infiltrate, and increased fibrillar collagen and collagen fiber bundles with interspersed fibroblasts. Later, the collagen becomes homogeneous, starting superficially with juxta-epithelial hyalinization. Advanced cases show loss of vascularity, hyalinization of collagen, dense fibrosis extending to underlying tissues with muscle degeneration, and complete replacement of loose connective tissues (areolar and reticular tissues) by fibrous tissue [Figure 4].

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Figure 4:

(A) Clinical presentation of oral submucous fibrosis displaying balancing of buccal mucosa (white arrow) (B) H&E stained section (4x) showing dense collagen fiber bundles and epithelial atrophy (black arrows). H&E: Hematoxylin and Eosin.

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Oral lichen planus and oral lichenoid lesion: The lack of clarity with the definitions of OLP and OLL has caused much of controversy. OLP is defined as “A chronic inflammatory disease associated with cell-mediated immunological dysfunction.” OLL is defined as “oral lesions resembling lichen planus but lacking typical clinical or histopathological appearances.” The histological distinction between some cases of OLP and OED with interface mucositis can be difficult. OLL includes atypical OLP, for example, unilateral lesions, lesions in close proximity to a dental restoration, lichenoid drug reaction, oral lesions developing after the intake of specific substances, and the oral lesions of graft versus host disease. Until recently, most studies assessing malignant transformation in OLP and OLL included cases with dysplasia, which is likely to have led to an overestimate of their malignant potential. Currently, most pathologists agree that if a biopsy shows clear evidence of OED, OLP is excluded.^48,49

Oral squamous cell carcinoma: Oral cavity cancer is the sixth most prevalent cancer worldwide, with SCC accounting for 90% of cases. Despite advances in treatment, OSCC is associated with high morbidity, tumor recurrence, and a low survival rate. It can arise from any oral mucosal site. In South and Central Asia, OSCC most commonly affects the BM because of the prevalence of areca nut/betel quid habit.

Patients with OSCCs may be completely asymptomatic, particularly at the early stage, whereas advanced tumors are associated with pain, alteration in sensation, restriction of tongue movement, or swallowing. OSCCs may appear as white, red, or mixed, flat/nodular/mass lesions of varying size. When present, advanced ulcers often have a raised and rolled margin; however, early OSCC can manifest as deceptively innocent appearing lesions. Other clinical findings may include tissue fixation and induration, mobility of teeth, trismus, bone destruction, and pathological fracture, dependent on the localization of the neoplasm.

OSCC is associated with tobacco smoke, alcohol consumption, and HPV infection. Poor general oral health and diets lacking in fruits and vegetables may act as contributory factors to oral SCC incidence and poor clinical outcomes.

OSCC may be preceded by OPMDs such as leukoplakia, erythroplakia, and OSF. The majority of OSCC are genetically unstable and exhibit significant chromosomal alterations and a high somatic mutation burden. Chromosomal losses at 3p, 8p, 9p, and 17p with gains at 3q, 5p, 8q, and 11q are reproducibly observed. Several large-scale sequencing studies have defined the mutational landscape for OSCC, with somatic mutations being observed in a number of genes, including TP53, CDKN2A, FAT1, NOTCH1, KMT2D, CASP8, AJUBA, NSD1, HLA-A, TGFBR2, USP9X, MLL4, HRAS, UNC13C, ARID2, and TRPM3.

The majority of oral cavity and mobile tongue cancers take the form of conventional keratinizing SCC. Nevertheless, there are other infrequent subtypes that can arise, including acantholytic SCC, adenosquamous carcinoma, basaloid SCC, carcinoma cuniculatum, lymphoepithelial carcinoma, papillary SCC, spindle cell SCC, and verrucous SCC [Figure 5]. Well-differentiated SCC contains large nests, cords, and islands of cells with pink cytoplasm and prominent intercellular bridging with round often hyperchromatic nuclei. Squamous pearls and dyskeratotic cells are also prominent.

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Figure 5:

(A) H&E stained section (4x) showing well differentiated oral squamous cell carcinoma comprises of large nests, cords, and islands of malignant epithelial cells and abundant keratin pearls (black arrow). (B) H&E stained section (10x) showing moderately differentiated oral squamous cell carcinoma comprises of small nests, cords, and islands of malignant epithelial cells and less amount keratin pearls in comparison to well differentiated type (black arrow). (C) H&E stained section (10x) showing poorly differentiated oral squamous cell carcinoma comprises of malignant epithelial cells with marked nuclear and cellular pleomorphism and nuclear hyperchromasia (black arrow). (D) H&E stained section (4x) showing verrucous carcinoma comprises of endophytic proliferation of epithelium with broad- bulbous rete ridges (black arrow). (E) H&E stained section (4x) showing papillary squamous cell carcinoma comprises of tumor cells displaying papillary growth pattern (black arrow). H&E: Hematoxylin and Eosin.

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Higher grade neoplasms may demonstrate marked nuclear and cellular pleomorphism, nuclear hyperchromasia, and mitotic figures (including atypical forms) and small islands or individual cells can be observed at the invasive front. Desmoplastic stroma with various degrees of inflammation can be found around invading tumor cell nests and islands. Perineural and lymphovascular invasion may occur, generally in poorly differentiated high-grade tumors. Adjacent mucosal epithelium may show various grades of dysplasia. Grading alone does not correlate well with prognosis. However, a number of specific features may have important biological relevance.^49–51

ORAL CANCER SCREENING IN DIFFERENT SETTINGS

Oral cavity cancer is often preceded by a clinical premalignant phase accessible to visual inspection. Thus, there are opportunities for early detection to reduce morbidity and mortality due to oral cavity cancers. The only randomized controlled trial (RCT) on oral cavity screening is in Trivandrum, India. This trial demonstrated the efficacy of oral visual inspection (OVI) conducted by trained health workers in reducing mortality due to oral cavity cancers among high-risk population, that is, those using tobacco and/or alcohol.⁵² Thus OVI, that is, systemic OVI under a bright light source and palpation and evaluation of the neck for any enlarged lymph nodes, is the screening tool used in most programs and studies to detect abnormal oral findings—oral cavity cancer or oral premalignant diseases.⁵³

Different settings and healthcare personnel for oral cavity screening: Oral cavity screening can easily be conducted in various settings such as primary care, dental clinics, and community outreach programs in urban, rural, tribal communities, workplaces, and also among special population groups.

• Primary care settings: Primary care physicians play a crucial role in detecting OPMDs and oral cavity cancers during routine check-ups. OVI remains the most common screening method. Research by Speight and Khawaja (2019) highlights the importance of training primary care providers in recognizing early signs of oral cancer, leading to improved detection rates and patient outcomes. However, limitations include the relatively low sensitivity and specificity of visual inspection alone.⁵⁴

• Under the National Program for Prevention and Control of Noncommunicable Diseases (NP-NCD, 2023), population-based screening (PBS) of persons aged 30 years and above for oral cavity cancer by community health officers (CHO) and associated team [Auxillary Nurse Midwife/Multipurpose Workers (ANM/MPWs)] at the Subcenter/Subhealth center-Health and Wellness center (SHC-HWC) has been incorporated in the operational guidelines.⁵⁵

• Dental clinics: Dental professionals are wellpositioned to identify oral cavity lesions and contribute to early cancer detection. A systematic review by Patton et al. (2018) on adjunctive techniques for oral cancer examination and diagnosis concludes that there is a lack of evidence to either endorse or disprove the use of adjuncts based on visual examinations. Thus, clinicians should depend on a comprehensive examination of the oral mucosa, accompanied by specialized consultation and/or conducting a tissue biopsy when diagnosing oral potentially malignant lesions (OPML).⁵⁶ Regular dental visits further facilitate the monitoring of suspicious lesions over time.

• Community-based outreach programs: In underserved communities, community outreach programs provide a platform for raising awareness and conducting screening. A study by Sankaranarayanan et al. (2019) emphasizes the effectiveness of utilizing trained community health workers for oral cancer screening in resource-limited settings.⁵² Community health workers use simple visual inspection techniques and refer screen positive cases for further evaluation. This approach ensures greater reach and early detection in populations with limited access to healthcare facilities. The feasibility of implementing screening in communities has been demonstrated in both urban and rural settings. However, linkages to referral, diagnostic, and treatment facilities need to be ensured.

  Tata Memorial Centre, under their Rural Outreach Program (TMC-ROP 2003–2012) carried out systematic cancer awareness and screening activities in rural districts of Maharashtra’s Konkan area through mobile education-cum-screening units (MESUs). Preliminary examinations were conducted at the village level by trained health workers and screen positive cases received confirmation of the diagnosis at their village through mobile-first referral level units (FRLU). The diagnosed cases received treatment at the designated nodal hospital within the selected districts.^57,58

  A community-based program for awareness and screening of oral cavity cancers was conducted among women residing in low socioeconomic areas of Mumbai. Screening was conducted by OVI by trained primary health workers (PHWs). This study helped in the identification of factors that influence adherence to oral cavity screening. Additionally, it highlights the effectiveness of various strategies in achieving high compliance rates, including conducting multiple home visits, extending personal invitations during health camps, implementing structured Health Education Programs, and utilizing a cost-effective visual inspection test administered by trained public health workers.⁵⁹

  Another community-based cancer awareness and screening program was conducted among urban women in Mumbai, India. Twelve slum clusters comprising of 138,383 population and 13,492 tobacco-using women were covered, and many oral precancers and cancers were detected and treated.⁶⁰

• Workplace-based programs: Occupational health programs have incorporated awareness, risk factor assessment, tobacco cessation, and targeted oral cancer screening to detect early precancers and cancers at workplaces. In a study conducted among 400 cab drivers in Mumbai, 255 (63.8%) were tobacco users and the majority consumed smokeless forms. All cab drivers were examined by OVI. This led to the detection of 112 oral precancerous lesions and one cab driver with invasive oral carcinoma.⁶¹

  A community-based oral cancer screening program conducted in municipal corporation wards of Mumbai city suggests the need of oral cancer screening along with tobacco cessation and control programs in manual laborers, as the prevalence of tobacco use is high among this group. In this program, 256 participants were screened for oral cavity cancers, and 23 oral precancers were diagnosed.⁶²

  With the smoke-free public places legislation that was implemented on October 2, 2008, smoking has been prohibited on public transport bus premises in India.⁶³ A Mumbai-based study conducted on 4000 public transport bus drivers, conductors, and other staff showed that the prevalence of tobacco use and oral precancers was high among the public transport bus employees in Mumbai. Hence, it was recommended that awareness, oral cavity screening, and tobacco cessation counseling needed to be incorporated within the annual health check-up of public transport bus employees.⁶⁴

  Workplace environments offer the potential to create opportunities and facilitate access to tobacco prevention initiatives. A single group study was conducted at the workplace to evaluate tobacco use prevention and cessation through a structured three-stage intervention program for tobacco users comprising education on the harmful effects of tobacco, oral cancer screening, and behavior therapy for tobacco cessation at the worksite for confectionary factory employees located in Mumbai, India, demonstrated good acceptance and participation by workers. The initiative was welcomed by employers for the overall health benefits. It also set momentum for an effective tobacco-free policy for the company.⁶⁵

  Following a one-year workplace tobacco cessation intervention, there was an observed regression of oral precancers in 80% of cases. This demonstrates the effectiveness of combining oral cavity screening with tobacco cessation efforts in a workplace setting.⁶⁶

• Rural and remote communities: Community-based oral cancer screening programs addresses disparities like lack of access to comprehensive healthcare services. Oral cancer screening is feasible and implementable. An oral cancer screening study conducted by Shankarnarayan et al. in Kerala demonstrated a positive predictive value of 1% and the program sensitivity for the detection of oral cancers of 76.6% with a specificity of 76.2%.⁶⁷

• Tribal and indigenous populations: Tribal and Indigenous communities may have distinct cultural and linguistic barriers that impact healthcare utilization. Collaborative initiatives such as engaging community leaders and incorporating culturally sensitive education materials have shown benefits.

  Healthcare providers’ (HCPs) perspectives at the primary healthcare (PHC) level, regarding the practicality of introducing a cost-efficient cancer screening initiative, with a specific focus on underserved rural and tribal regions lacking adequate access to cancer services, was assessed in the study done in the tribal block of Maharashtra. The study recommended the need of continuous support of primary care providers during the actual implementation of the program, along with training and the establishment of feedback mechanism from tertiary care to enhance the engagement of the providers in patient management.⁶⁸

• Special populations:

  1. Oral cancer screening among school children: A tobacco cancer awareness program conducted among school children in the rural areas of Ratnagiri district of Maharashtra State in India demonstrates the effectiveness of increased awareness about the adverse consequences of tobacco use and cancer among school children. Subsequent research is required to assess whether educating school children influences the broader community’s comprehension of this disease.⁶⁹

  2. Oral cancer screening in street populations: Street populations, including the homeless and those with unstable housing, face unique challenges that hinder access to healthcare services, including oral cancer screening. Innovative outreach initiatives have been developed to address these barriers.

  3. Correctional facilities: Oral health services in correctional facilities are often limited. Implementing oral cancer screening within these settings can contribute to early detection and treatment.

  4. Refugee and immigrant communities: Refugees and immigrants often encounter challenges related to language, cultural differences, and unfamiliarity with the local healthcare system. In a study conducted by Lucy L about betel nut usage among refugees, 48 participants with betel nut familiarity were interviewed. The majority of them were South and Southeast Asians. This study illustrated that there were gaps in understanding about the usage of betel nut and its consequences on health.⁷⁰

• Teledentistry and telemedicine: Advancements in telehealth have paved the way for remote oral cancer screening. Teledentistry and telemedicine enable HCPs to conduct preliminary assessments and offer guidance to patients in realtime. A systematic review by Estai et al. (2020) highlights the potential of teledentistry in enhancing access to oral health services, particularly in rural and remote areas. While not a replacement for in-person examinations, telemedicine platforms can aid in triaging patients for further evaluation.⁷¹

• National oral cancer screening program undertaken in Taiwan: Taiwan is the only country in the world to initiate a sustained national oral cancer screening program. Screening is currently offered to high-risk groups, that is, betel quid chewers (including ex-chewers) and smokers. This was the first study to use risk-stratification modeling to target high-risk patients.⁷²

• NP-NCD Program incorporating oral cavity screening in India: The national program for prevention and control of noncommunicable diseases (NCDs) launched in 2010 is being implemented under the National Health Mission (NHM). Operational guidelines have been laid for the years 2023–2030.⁵⁵ The goal is to provide assistance for Program management and capacity building of health practitioners at all levels of primary and secondary healthcare. The PBS and opportunistic screening of common NCDs and common cancers, including cancer of the oral cavity, was initiated in 2016, and was scaled up in a phased manner.

Oral cancer screening services are undertaken at the subcenter level by CHOs and the appropriate referral system has been strengthened. Activities and interventions at various levels by individuals, community-level forums like Village Health Sanitation and Nutrition Committee (VHSNC)/Mahila Aaarogya Samiti (MAS), Jan Aarogya Samiti (JAS), Self-Help Groups (SHG), and local bodies in both rural and urban areas need to be strengthened and established as a platform for community awareness and promotive and preventive care activities. Frontline workers, Accredited Social Health Workers (ASHA), MPW/ANM need to develop skills for primary, basic diagnostic and community-level preventive care for NCD-related issues.

Oral cancer screening methods vary across healthcare settings, each with its advantages and limitations. While visual inspection remains a fundamental tool, adjunctive technologies are sometimes used in dental clinics; community outreach programs and telemedicine extends accessibility to screening.

Collaborative efforts between primary care physicians, dental professionals, and community health workers are essential to ensure comprehensive oral cancer screening. Combining the strengths of these different approaches holds the promise of earlier detection, better patient outcomes, and, ultimately a reduction in the global burden of oral cancers.

Evidence and guidelines: The only RCT for oral cancer screening from India showed a reduction in mortality from oral cancers among high-risk individuals 35 years and older when they received three rounds of screening by OVI conducted by trained health workers at three-year intervals. This trial suggests that OVI conducted by well-trained health workers among individuals ≥35 years and are tobacco and/or alcohol users at three yearly interval is beneficial.⁶⁷

Under the current NP-NCD, 2023, PBS of persons aged 30 years and above for oral cavity cancer by CHO and associated team (ANM/MPWs) at the SHC-HWC has been incorporated in the operational guidelines.

In the National Program for Prevention and Control of Noncommunicable Diseases (NP-NCD, 2023), CHO and associated teams (ANMs/MPWs) would provide primary-level care at the HWC in rural areas while dedicated Medical Officer (MO) would be posted at Urban HWCs (UHWCs) to undertake screening for individuals ≥30 years at five yearly interval.⁵⁵

According to the Cochrane review, there is not enough evidence to decide whether screening by OVI reduces mortality due to oral cancers, though there is some evidence that it might help reduce death rates in patients who use tobacco and alcohol and there is no evidence for other screening methods for oral cancers.⁷³

Based on all of the above literature, oral cavity cancer screening is suggested at least for individuals using tobacco and/or alcohol and ≥30 years at three yearly intervals by any well-trained medical or paramedical personnel.

CURRENT EVIDENCE ON ORAL CANCER SCREENING PRINCIPLES AND TOOLS—HEALTH ECONOMIC EVALUATION OF SCREENING TOOLS

A recent review of the economic evaluation of oral cancer screening programs⁷⁴ revealed that there is still limited evidence on PBS approaches and their cost-effectiveness, which limits institutionalization of those measures at scale by the policymakers. The review of six studies included randomized controlled study, retrospective observational study, decision analytic model, and Markov state transition model, and explored the initiation of screening the population between the ages of 35 and 40 years. Some countries, such as Taiwan have integrated the screening through biennial oral mucosa examinations for its high-risk population within its public healthcare,⁷⁵ whereas some countries like USA followed the annual screening of high-risk populations.⁷⁶

The programmatic cost components included training, recruitment, the screening process, administrative work, and the provision of educational messages in the randomized control study in India.⁷⁷ Some studies included extensive direct and indirect medical costs.⁷⁸ The total societal cost included research, diagnostics, treatment, and loss of patient productivity. The cost excluded the program development and management costs. The outcomes evaluated in these studies were for over a year and also considered a lifetime horizon to assess the impact of screening initiatives on the variable MTRs of OPMD to be established over the life span of patients. Another approach estimated the long-term outcomes by calculating the equivalent lives saved according to a 25-year life expectancy and changes in quality-adjusted life years (QALYs).⁷⁹

Another recent study in India⁸⁰ evaluated the cost-effectiveness of commonly used screening techniques, namely conventional oral examination (COE), toluidine blue staining (TBS), oral cytology (OC), and light-based detection (LBD) devices like Velscope and ViziLite plus in the Indian scenario through economic modeling of the population (>30 years). The screening intervals considered were three, five, and ten years for each screening strategy and compared with the no screening cohort. The cost of screening strategies was estimated using the time, salary cost, and effort by the auxiliary nurse midwifery, the number of screenings per day, and the cost of consumables used. Support activities costs included invitation and organization for the screening, administration, registration, training, supervision, and miscellaneous activities required for the screening process. The cost of diagnosis was estimated considering the standard protocol of oral examination, that is, the cost of consultation during outpatient department visits, and the biopsy cost.

The outcomes considered were incidence of oral cancer, oral cancer deaths averted, the total cost incurred, total QALYs gained, and incremental cost-effectiveness ratio (ICER) for various screening techniques and at different intervals. The results showed that massscreening/high-risk screening had a lesser number of oral cancer incident cases and oral cancer deaths as compared to no no-screening. Among the screening strategies, it was observed that high-risk screening was cost-effective compared to the mass screening at various intervals. The no screening arm had the maximum number of new cases (5674) and deaths (1180). Massscreening techniques (number of incident cases), namely LBD three years (3272), had the least number of incident cases, followed by OC three years (3277), and COE three years (3310) and averted deaths (450).

The no screening arm incurred a lifetime cost of USD 2,677,683.84 (per 100,000 population) while high-risk screening incurred lesser costs across all comparisons. Amongst various screening techniques, COE HR ten years incurred the least lifetime cost of USD 2,292,779.25, and OC three years of USD 7,284,185.66 incurred the maximum lifetime cost. OC and LBD at three-year intervals also yielded an incremental QALY gain of 6679 QALYs. The high-risk screening was cost saving at all levels of screening coverage than mass screening, which is cost saving only at 10% and above coverage. Among the techniques, the high-risk screening by COE at ten years was the most cost-saving approach.

The budget impact analysis indicated that the “implementation of nationwide oral screening using conventional oral examination for high-risk population above 30 years of age at 10-year interval would account for only 0.03% of annual healthcare budget of India in the year 2022–2023.” Hence for Indian setting at national scale, COE for high-risk population above 30 years at ten-year interval is recommended as the screening strategy.

CURRENT STATUS OF INFRASTRUCTURE, FACILITIES, TECHNOLOGIES, POLICIES, PROGRAMS IN INDIA

As per the recent reports of the Healthcare Access and Quality Index (HAQI) conducted in 2016, India ranked 145th out of 195 countries, trailing behind its neighbors Sri Lanka (71st) and Bangladesh (132nd).⁸¹ The HAQI India rank indicates that a majority of the country’s population does not have access to high-quality or even acceptable standards of healthcare. Both access and quality of healthcare are essential components for achieving universal health coverage (UHC).⁸² However, progress toward UHC in India is hampered due to a very high level of OOPE on health, especially in cancer care,⁸³ leading millions of people toward impoverishment.

NATIONAL AND INTERNATIONAL GUIDELINES FOR ORAL CANCER MANAGEMENT

Oral cancer accounts for 8.8% of all cancer-related deaths. Most of these cases, nearly 90%, are SCCs. The choice of the treatment approach for oral cancer depends on the stage of the disease, and if diagnosed in early stages, curative therapies such as surgery are preferred. Therefore, it’s essential to diagnose early and precisely through a thorough physical examination and various imaging techniques. This evaluation process should involve a multidisciplinary team and should be thoroughly reviewed before settling on the final treatment plan.

Modern technology has introduced several imaging methods, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography, and positron emission tomography (PET)-CT. Among these, CT and MRI are typically preferred for evaluating the local and regional extent of the disease. Furthermore, during the staging process, it’s advisable to conduct an endoscopic examination of the upper digestive tract because approximately 7% of oral cancer patients are known to have a concurrent second primary lesion in this region.¹⁰⁰

Typically, the primary treatment for OSCC is surgery. The primary goal of surgical resection is to ensure complete removal of the tumor tissue. However, the potential negative impacts on appearance and functionality due to the extent of the disease and the necessary surgical removal stress the importance of using less invasive surgical methods, such as sentinel lymph node (SLN) biopsy, especially in early stage cases, to reduce surgical-related complications. Additionally, for patients at high risk of the cancer returning, RT or a combination of chemotherapy and RT (chemoradiation or CRT) is often added as a adjuvant treatment.¹⁰¹

ORAL CANCER IN NATIONAL PROGRAM FOR NCD IN CONTEXT OF ORAL CANCER: CHALLENGES AND BARRIERS

India is experiencing a rapid health transition with a rising burden of NCDs. According to a WHO report (2002), cardiovascular diseases (CVDs) will be the largest cause of death and disability in India by 2020. Overall, NCDs are emerging as the leading cause of deaths in India, accounting for over 42% of all deaths (Registrar General of India). NCDs cause significant morbidity and mortality both in urban and rural populations, with considerable loss in potentially productive years (aged 35–64 years) of life. There are an estimated 2,500,000 cancer cases in India. According to the National Commission on Macroeconomics and Health (NCMH) Report (2005), the crude incidence rate (CIR) for oral cancer is 11.8 (among both men and women) per 100,000 population.¹⁰²

The Government of India launched the NCCP in 1975, and revised the strategies during 1984–1985, which stressed on primary prevention and early detection of cancer. In order to prevent and control major NCDs, the NPCDCS was launched in 2010 with the focus on strengthening infrastructure, human resource development, health promotion, early diagnosis, management, and referral.

During the period 2010–2012, the program was implemented in 100 districts across 21 States. The implementation strategies are:

• Health promotion through behavior change with the involvement of the community.

• Outreach camps for opportunistic screening at all levels in the healthcare delivery system. Management of chronic NCDs, especially cancer, through early diagnosis, treatment, and follow-up.

• Build capacity at various levels of healthcare for prevention, early diagnosis, treatment, behaviour change communication (BCC)/information education and communication (IEC), operational research, and rehabilitation.

• Provide support for diagnosis and cost-effective treatment at primary, secondary, and tertiary levels of healthcare.

• Provide support for the development of a database of NCDs through a robust surveillance system and to monitor NCD morbidity, mortality, and risk factors.¹⁰³

However, the key challenges are with the availability of trained human resources for the screening of the NCDs essential for early detection, low budget allocation and utilization, lack of access to diagnostics, and regular supply of essential medicines. There is also a poor focus on health promotion, with lack of multisectoral participation, surveillance, regular supervision, monitoring, and evaluation of the program at different levels of healthcare delivery. Kedar et al. (2019), in their study on the views of health personnel regarding cancer screening programs, also reported that lack of human resources and increased workload on existing labor was considered a challenge in the implementation of the cancer screening program. Also, examination of the oral cavity for the screening of oral cancers requires an extra of 7–10 minutes, which can be challenging in the already overburdened public health facilities.^104,105

A study conducted in South India showed that the most important missing link in program implementation is the unavailability of MOs and other relevant staff.¹⁰⁶ The need for training for effective implementation of cancer screening programs was emphasized by Patil et al. (2019), who in their study among HCPs in tribal areas of Maharashtra reported that lack of training was perceived as a major barrier. Many secondary care facilities lack provision for biopsy and diagnostics.¹⁰⁷ Another challenge encountered is streamlining referrals and their follow-up. Meena et al., in their study conducted in two rural health facilities of Jodhpur, reported that complete treatment and assistance could not be provided to the patient who was found to have cancerous or precancerous lesions due to resource constraints.¹⁰⁸

Ramani et al. (2023) have identified four key priority areas, which promote health services for cancer control:

• Capacity building in oncology-related health service research in low- and middle-income countries (LMICs) and the relevant policy and planning

• Developing high-quality sources of health data (e.g., population-based cancer registries) which can identify the process and outcomes of cancer management for achieving quality cancer control

• Oncology-related economic evaluation of screening, training, and treatment as well as rehabilitative services.

• Explore high-quality models of cancer control^109–111

The unique challenges posed by the rise in NCD morbidity require horizontal as well as vertical integration of the health systems with new services focused on oral cancer control. It is important to focus on understanding the implementation and its barriers so that these challenges are met timely.

CAPACITY BUILDING AND TRAINING INITIATIVES IN ORAL CANCER

Oral cancer ranks among the top 20 most widespread cancer types globally, contributing to elevated rates of both mortality and morbidity.¹¹² A great increase in new cases is projected in developing countries (China, India, and Brazil), considering the period 2020 through 2040, ranging from 80.1% to 97.8%.¹¹³

Unmet needs: A comprehensive review encompassing studies conducted in both developed and developing nations pinpointed the primary reasons behind delayed oral cancer diagnosis in patients. These were the challenges of visualizing or identifying oral lesions, coupled with the absence of symptoms in the initial stages of these lesions.¹¹⁴ This may be due to limited awareness within the population regarding oral cancer, its associated risk factors, and its distinctive attributes. Such lack of awareness might cause individuals to overlook the initial indications and symptoms, thus amplifying delay in the search of specialized care.¹¹⁵

Roughly, 50% of oral cancer patients are reported to consult a HCP within one to two months on recognizing the symptoms; however, an estimated 20–30% of patients delay seeking assistance for over three months.¹¹⁶

The time between the patients’ first awareness of symptoms of oral cancer and their first consultation with a HCP regarding those symptoms is considered to be the duration of patient delay.¹¹² This is distinct from “professional delay” (time from first consultation with a HCP regarding a sign/symptom to definitive diagnosis) and “total delay” (time from first awareness of a sign or symptom to definitive diagnosis).¹¹⁶

Capacity building: This involves empowering individuals and organizations with the skills, knowledge, and resources necessary to address complex health issues such as oral cancer. This aids in improving their competence in prevention, early detection, and its management, including supportive care. The four approaches of capacity building¹¹⁷ are:

• Top-down organizational approach: This begins with changing agency policies or practices. Top management’s involvement in the change program helps establish a sense of urgency in change.¹¹⁸

• Bottom-up organizational approach: For example, provision of skills to staff. Bottom-up policy implementation theory states that managers make meaning of top-down reforms. The conditions in which the staff work, their own experience, discretion, and tacit use of knowledge transform policy into practice.¹¹⁹

• Partnerships approach: This comprises strengthening the relationships between organizations. Regardless of one’s area of specialty and background, members of partnership passionately reduce inequalities in health and social circumstances, thus improving the community’s quality of life.¹²⁰

• Community organizing approach: Individual community members are drawn to forming new organizations or linking up with the existing ones to improve the health of community members. Moreover, community engagement can enhance linguistically and culturally appropriate measures and field piloting.¹²¹

BUDGET FOR VARIOUS ORAL CANCER INITIATIVES IN INDIA

Oral cancer imposes a significant fiscal burden on a national, institutional, and individual level. Funding of cancer care in India is a complex mixture of state and government accountabilities, with the government shouldering most of the responsibility. Oral cancer as such, has not been given a separate budget in India. However it has been covered under various facilities of the government, schemes, and programs for cancer. The allocation also has not been clear regarding the distribution of funds for cancer care and cancer research.

Assuming the Centre and State governments spend 30% and 70%, respectively, of the total government spending on healthcare, in 2023–2024, the combined budgeted expenditure on the health sector would be 1.18% of GDP. The budget estimate for 2023–2024 is given in Table 1.

The combined budgeted expenditure on the health sector by the Centre and State governments has increased from 2020 to 2021.^134,135 Cancer-specific spending in India has increased from INR 115 million in the sixth plan (1980–1985) to INR 28,719 million and INR 60,000 million in 11th and 12th five-year plan, respectively.^136–138 This increasing trend of GDP may also impact the increase on the budget allocation for various programs and schemes for cancer.

Oral Cancer

• Treatment: India spent approximately USD 322 million (Rs. 23,860 million) in 2020 on oral cancer treatment, paid for by insurance schemes, government and private sector spending, out-of-pocket payments and charitable donations or a combination of these.^139,140 A significant portion of the healthcare budget allocation the government made is not linear to the oral cancer treatment independent report (mouth cancer treatment cost in India ranges from INR 60,574 (USD 758) to INR 504,893 (USD 6,318) with an average of INR 280,096 (USD 3,505) as shown in Figure 6.^141,142

  Under CGHS (Central Government Health Scheme) and DGHS (Delhi Government Employees Health Scheme), the cost of biopsies to surgeries for head and neck cancers (INR 5,750–47,610), RT (INR 5621–169,068), and CT (INR 992–1,058) has been provided.¹⁴³

  Under the PMJAY scheme, the drug cost in medical oncology ranges from INR 2600 to INR 18,900, from INR 5,500 to INR 117,000 for various radiation oncology procedures, palliative medicine therapy costs from INR 2,300 to INR 10,300 per day for various services, and different OMFS surgeries cost varies from INR 2,700 to INR 1,800 [Supplementary Material-Annexure 2].

  Supplementary Material-Annexure 2

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• Screening: Budget impact analysis showed that oral screening using COE for high-risk population at ten-year intervals costs lower than the annual healthcare budget of India for the year 2022–2023 (0.03% of annual healthcare budget of India [862,006.5 million]).¹⁴⁰ First year INR 25,727,541,030.81 and second year INR 28,300,295,133.90.

• National Health Programs/schemes for cancer in India: No separate budget for oral cancer has been given by various schemes and programs in India. But oral cancers have been considered under the NCDs and cancer category for funding. NCCP (now under NP-NCD) in India has also seen a modest rise in spending during the past decade from 48 × 107 Indian rupees (USD 7·7 million) to more than 140 × 107 Indian rupees (USD 22·6 million) in 2004–2005.^144,145

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Figure 6:

The cost of oral cancer treatment in India (Source: clinicspots.com) There also has been observation of varying trends in the rates for cancer treatments from one scheme to another scheme in 20,083 and these rates are lower than the cost incurred by patients in a study done at Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh (2018).

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Existing schemes under NCCP as on June 1, 2008¹⁴⁶:

1. Recognition of new RCCs: A onetime grant of INR 50 million was provided for new RCCs.

2. Strengthening of existing RCCs: A onetime grant of INR 30 million was provided to the existing RCCs to further strengthen the cancer care services.

3. Development of oncology wing: Government Hospitals and Government Medical Colleges are provided with a grant of INR 30 million for the development of the oncology wing.

4. District cancer control program (DCCP): A grant-in-aid of INR 9 million spread over a period of five years was provided per DCCP proposal.

5. Decentralized NGO scheme: A grant of INR 8,000 per camp was provided to the NGOs for IEC activities.

National Health Mission: Under the NHM budget, INR 220,945.7 million allocated for 2023–2024 covers the National Tobacco Control Program (NTCP), National Oral Health Program (NOHP), and Noncommunicable Disease Program.^147–149

1. National Program for prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS) program or now known as NP-NCD.^150–152 Total cost of the program for period 2012–2017 was INR 80,960 million (share of Government of India is INR 65,350 million and that of State Governments is INR 15,610 million).

   • For the cancer component, there is the TCCCs scheme, which aims at setting up/strengthening 20 SCIs and 50 TCCCs for providing comprehensive cancer care in the country. Under the scheme, there is a provision for giving a “onetime grant” of INR 1,200 million per SCI and INR 450 million per TCCC, to be used for building construction and procurement of equipment, with the Center to State share in the ratio of 60:40 (except for North-Eastern and Hilly States, where the share is 90:10).¹⁴⁵

   • Earlier (approximately two years), 1.5–2 million per district were allocated under equipment head for the three cancers (breast, cervical, and oral).

   • A total of 5 million per district per year for equipment of three cancers (breast, cervical, oral) and 2.5 million per district per year for drugs for three cancers.

2. National Tobacco Control Program: NTCP in 400 districts across India with a budget allocation of INR 650 million (USD 8.8million) for the year 2018–2019.¹⁵³

3. National Oral Health Program: A total approval of INR 250 million¹⁴⁶ for 26 states/UTs has been given to support the proposed activities of NOHP. Grants have been released to the states/UTs under the health system strengthening (HSS) of Mission flexipool under NHM. Oral cancer has been one of the major components of NOHP.¹⁵⁴

4. Ayushman Bharat: AB-PMJAY^147–149 has been allotted INR 72 billion for the FY 2023–2024; INR 7.61 billion was spent in 2021–2022.¹⁴⁸ Surgical oncology and radiation oncology for oral and maxillofacial region has been included in the list of services.

5. Others: Furthermore, since 2007, a large amount of money has been pooled toward cancer care by the Government of India through various publicly sponsored health insurance schemes (Rashtriya Swasthya Bima Yojana, Rajiv Gandhi Jeevandayee Arogya Yojana, Rajiv Aarogyasri Health Insurance Scheme).^154–156 Also, certain states such as Punjab provide cashless cancer treatment in various public and private sector hospitals.¹⁵⁷

   • The Chief Minister’s Comprehensive Health Insurance Scheme in Tamil Nadu: INR 400,000 for four years in a recognized cancer center.

   • The Vajpayee Arogyashree Scheme is a state insurance scheme that was introduced in Karnataka state. A maximum limit of INR 150,000 is set for a family of five per year in seven streams, including cancer.

   • Affordable Medicines and Reliable Implants for Treatment (AMRIT)

   • Rashtriya Arogya Nidhi (RAN)

   • Ayushman Bharat Arogya Karnataka scheme (ABArK)

KEY ISSUES/GAPS IDENTIFIED IN CURRENT SITUATION AND CONTEXT OF ORAL CANCER IN INDIA

The Indian subcontinent, especially India because of its large population and widespread tobacco use, has long been regarded as the global epicenter of oral cancer. A recent study concluded that India has the highest incidence rates of mouth and oral tongue cancer in both males and females among 185 countries.¹⁵⁹

Diverse factors influence oral cancer development in India. The primary risk factor encompasses tobacco use (smoking and smokeless varieties), which is linked to nearly 90% of all oral cancers.¹⁶⁰ The other key risk factors are heavy alcohol consumption, betel quid and areca nut chewing, poor oral hygiene, HPV infection (especially HPV-16 and HPV-18), inadequate dietary habits, genetic predisposition (especially with a family history), prolonged UV radiation exposure (particularly in outdoor occupations), occupational exposure to wood dust, asbestos, and certain chemicals and regional variations influenced by Socio-economic status, healthcare access, and cultural practices.¹⁶¹ In India, areca chewing without tobacco is associated with a threefold increased risk of head and neck squamous cell carcinoma (HNSCC), while combining areca chewing with tobacco resulted in an eightfold risk, with a reported positive dose–response curves.¹⁶²

Despite the fact of the above risk factors, where oral cancer and its consequences can be prevented, treated, and controlled, there exists a significant implementation gap in India. Though many efforts have been made till now to combat the risk factors and disease, the burden it imposes, in terms of incidence, mortality, survival, and the determinants of disease as well as the limited healthcare resources, creates significant gaps in control of these cancers.

The gaps are discussed under the broad headings of [Figure 7]:

1. Prevention: Health promotion, screening, registries, and programs

2. Management

3. Patient perspectives

4. Research

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Figure 7:

Gaps in oral cancer care in India.

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RECOMMENDATIONS TO BRIDGE THE CRITICAL GAPS IN TREATMENT MANAGEMENT INCLUDING PALLIATIVE CARE IN ORAL CANCER

Oral cancer is predominantly a regional disease that tends to infiltrate adjacent bone and soft tissues and spreads to the regional lymph nodes in the neck. Given the skills, expertise, and infrastructure required for staging and treatment with minimal physical, functional, and cosmetic morbidity, oral cancer treatment is usually provided in specialized cancer hospitals, such as comprehensive cancer centers, or in hospitals at the highest level of health services.

KEY GAPS IDENTIFIED IN CURRENT INFRASTRUCTURE, HEALTHCARE FACILITIES, HUMAN RESOURCES, TECHNOLOGIES, POLICIES, PROGRAMS IN ORAL CANCER

Oral cancer, a significant health concern in India, presents a daunting challenge for public health systems. Despite concerted efforts, substantial gaps persist across infrastructure, facilities, human resources, technologies, policies, and programs with regard to oral cancer management.

• Infrastructure: India has a three-tier healthcare delivery system consisting of primary, secondary, and tertiary, which was established to provide basic healthcare services accessible at a grassroots level. HWCs, PHCs, community health centers (CHCs), and district hospitals are the cornerstone of healthcare delivery. Unfortunately, they often lack specialized resources for early detection, diagnosis, and treatment of oral cancer. Deficiencies in oral cancer screening tools, biopsy facilities, and radiotherapy equipment hinder effective intervention.^179,180

  A case study from Maharashtra suggested that the CHCs have been under the radar of criticism with regard to their inability to deliver quality services as per the Indian Public Health Standards (IPHS). The main reasons are the lack of proper human resources, inadequate infrastructure, and facilities.¹⁸¹

• Human resources: A dearth of adequately skilled healthcare professionals well versed in oral cancer management is a pressing concern. The shortage extends to oral maxillofacial surgeons, oral medicine, radiologists, oral pathologists, and public health dentists who are all essential for accurate diagnosis and treatment. Furthermore, empowering healthcare workers across all levels with oral health education is pivotal in identifying and referring potential cases.^182,183

• Technologies: Cutting-edge technologies, like AI-driven diagnostic tools, teledentistry for remote consultations, and telemedicine for expert opinions, offer promise in bridging gaps in oral cancer care, especially in remote areas where the prevalence remains high but goes unnoticed. Nonetheless, integrating these technologies into the healthcare system faces challenges due to awareness gaps, infrastructure, and regulatory limitations.

• Policies and programs: While broader cancer policies exist in India, targeted policies addressing oral cancer’s prevention, early detection, and treatment are often absent. Tailored programs aimed at high-risk groups, such as tobacco and alcohol users and workplace-based screening are instrumental in reducing oral cancer incidences. A comprehensive, multisectoral approach involving health, education, labor, and other stakeholders is the need of the hour.¹⁸⁴

Hence, addressing these gaps necessitates collaborative efforts between government bodies, healthcare institutions, NGOs, and international agencies. Partnerships can facilitate funding, capacity building, and knowledge enhancement, ultimately improving the overall oral cancer care ecosystem. In conclusion, the challenges in oral cancer management in India are multifaceted and require a comprehensive and holistic approach. By addressing these gaps in infrastructure, human resources, education, policies, and collaborative efforts, India can make significant strides in reducing the overall burden of oral cancer and ultimately improving public health.

RECOMMENDATIONS TO BRIDGE CRITICAL GAPS in INFRASTRUCTURE, FACILITIES, TECHNOLOGIES, POLICIES, PROGRAMS IN ORAL CANCER

Generally, death rates for oral cancer exceed those of many other cancers; only half of all patients survive the first five years after diagnosis. The five-year survival rate for Stage I oral cancer is of approximately 80%, while the corresponding value for patients with advanced disease (Stages III/IV) is approximately 20%.¹⁸⁵ Despite advances in diagnosis and treatment, this number has not changed in the past decades. In addition, the impacts of oral cancer, even after treatment, result in severely reduced quality of life for those who survive (FDI, 2015).¹⁸⁶ Only 0.2% of the population are screened for oral cancer in India NFHS-5.¹⁸⁷

The programs in India for oral cancer reflect the recognition of the need to collect cancer-related data and prioritizing the management of various cancers; there are various lacunae that exist while addressing the menace of oral cancer in India.

The recommendations to bridge these lacunae are discussed at three levels of approach [Figure 8]:

1. Macro (Policy and Programs)

2. Meso (Systems and Research)

3. Micro (Patients and Care Providers)

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Figure 8:

Recommendation to bridge the gap of for oral precancer and cancer care in India.

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ii. Meso (systems and research)

1. Situation analysis of the existing healthcare systems and budget and research for oral precancer and oral cancer need to be carried out. The existing data is sparse and is mainly merged with the other cancers. In order to plan and provide administrative and financial forecasts, an urgent evaluation is required of the existing infrastructure and manpower under the NCCP.

2. Healthcare systems

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     Improving infrastructure to deliver quality services as per the IPHS. This includes increasing the number of specialized cancer treatment centers, equipping them with state-of-the-art diagnostic and treatment equipment, and ensuring access to specialists in oral oncology.

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     A four-tier healthcare delivery system for cancer care with multisectoral approach and PPP model is proposed in Figure 9.

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     Expansion of cancer registries and strengthening of existing registries in India is imperative as only 38 population-based cancer registries and 268 hospital-based cancer registries under National Centre for Disease Informatics and Research (NCDIR)/NCRP cover only 10% of the population. These registries also need to set up in the existing dental colleges and hospitals with linkages to respective state registries.

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     Dental colleges and hospitals can also become a center for comprehensive oral care and act as an early detector of OPMD’s and oral cancer.

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     There is a pressing need to strengthen the existing public healthcare systems: the infrastructure, manpower, and facilities to screen, diagnose, and manage the patients in effective manner.

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     Data should be captured to maintain longitudinal health records of population right from screening stage and ensuring tracking and follow-up with patients for effective referrals. Digitalization of the facilities in terms of patient details entry, treatment, and follow-up will facilitate the easy access and flow of information between databases during referral. Mandatory notification of data on from all healthcare systems in India should be implemented. Use of mhealth and robust data collection software or apps will also empower the ASHAs, ANMs, Mos, and specialists with data regarding the patient.

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     The availability of screening, diagnostic, and treatment support equipment, such as CT and PET-CT, is also highly underpenetrated in India requiring significant ramp up.¹⁹⁰

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     With the availability of only 640 radiotherapy installations in the country currently, there is a requirement of 850–900 additional RT installations in the current state, but the need will increase with increasing incidence of oral cancer.¹⁹⁰ PPPs can help reduce the load on public healthcare systems.

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     Tobacco and areca nut use cessation counseling capacity needs to further penetrate all the areas of the country to reduce gaps. Dentists and dental organizations are actively to be involved.

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     Referral and networking of centers to be strengthened.

3. Oral cancer care (treatment, palliative, and rehabilitation)

   • Developing the four-tier care delivery systems for oral cancer will help to reduce the cancer care access in rural areas and reduce the cost of care.

   • Provision of support for diagnosis, accessibility, and cost-effective treatment at all levels of healthcare or oral precancer and cancer.¹⁹¹

   • Histopathological diagnosis, being the gold standard for oral cancer detection can be a boon for early diagnosis and help in treatment planning; hence, should be made more accessible to the rural population.

   • The cost of care for many patients has come down due to some form of insurance/government-sponsored health coverage programs (54%), but the gaps in the coverage of different states needs to be minimized.¹⁹² The OOPE on drugs and diagnostics can be reduced by the PPP model of care and increasing the coverage of insurance for effective treatments. Include PET-CT as a separate procedure for reimbursement across the entire state government scheme.

   • Evidence-based detection, diagnosis, management, palliative, and rehabilitation should be emphasized. Guidelines and standard operating procedures (SOPs) should be framed and circulated for uniform training and implementation.

   • Emphasis on early diagnosis of OPMD lesions and oral cancer: More facilities should be enhanced in every healthcare system for early diagnosis. Training should be done for doctors and paramedical staff for earlier lesions of oral cancer. Encourage technology-driven tools like AI, Apps, and early screening detection kits.¹⁹³

   • Focus on improving palliative care services for oral cancer patients, including pain management, psychological support, and rehabilitation programs. Collaborate with healthcare professionals and organizations specialized in palliative care to ensure comprehensive support for patients throughout their cancer journey.

   • Guidelines for risk factor assessment and predictive analysis for OPMD and oral cancer should be developed.

   • Telemedicine, electronic patient records, robotics, AI-backed upskilling methods, daycare chemo, home care, and so on are some of the strategies that are already in some places to address these care gaps but needs to be implemented throughout India.

4. Human resources

   • More oncologists should be deployed at cancer care centers. To meet the demand of oncologists, oral surgeons should be deployed at centers. Measures to be taken to increase the availability of oral healthcare team (oral and maxillofacial surgeons, oral medicine and diagnostic specialists, oral pathologists, and public health dentists) at all levels of healthcare settings, including community settings.

   • Adequate workforce planning and timely recruitment at CHC and district hospitals (DH) will help meet gaps in the workforce.

   • Sensitization, capacity building, and training of all healthcare personnel involved in oral cancer care on a regular basis with evaluations and feedbacks should be carried out.

   • Training of paramedical staff, auxiliary nurses, and ASHA workers for screening and providing counseling to oral cancer patients, thus facilitating early diagnosis and prompt treatment to increase survival rates and reduce economic implications.

5. Research

   • Research priorities to be identified, laid down and circulated based on situation analysis.

   • Support collaborative efforts between government institutions, research organizations, and private industry to develop innovative approaches, technologies, and therapies.

   • The evidence generated should be communicated among all stakeholders, including the general population.

   • Cost-effective technology and innovation should be encouraged for research and adopted for the screening, diagnosis, management, and rehabilitation of patients.

   • Biomarkers, both diagnostic and prognostics; biosensors; targeted therapy and immunotherapy areas need to researched more.

6. Multisectoral partnerships (collaboration and partnerships)

   • Foster collaborations between government bodies, HCPs, NGOs, and international organizations to pool resources and expertise in addressing the challenges associated with oral cancer. Encourage PPPs to accelerate progress in research, prevention, and treatment initiatives.

   • All organizations and agencies working for oral cancer partner with the dental colleges and hospitals.

   • Empower general practitioners and up-skill specialists (dentists, ENT, etc.) to play an effective role as gatekeepers.

   • Oral cancer should be part of healthy and safe schools, workplaces, and public institutions and health facilities.

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Figure 9:

Proposed oral cancer care in India. MoHFW: Ministry of Health and Family Welfare, PHC: Primary Health Centre, CHC: Community Health Centre, NGO: Non-governmnetal Organizations, VHC: Voluntary Health Agencies, CSO: Civil Society Organizations, PPP: Public Private Partnership.

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OPERATIONAL DEFINITIONS

1. Oral cancer: Oral cancer is defined as the cancer of the lip, mouth, and tongue, to include the anatomic description of the oral cavity. This case definition is adopted, and conforms to the definitions of oral cavity cancer by the International Classification of Diseases (ICD) Coding scheme, World Health Organization (WHO) case definitions, and International Agency for Research on Cancer (IARC).

2. Oral potentially malignant disorder: Any oral mucosal abnormality that is associated with a statistically increased risk of developing oral cancer (The WHO Collaborating Centre for Oral Cancer Workshop, 2020).

3. Screening: The identification of unrecognized disease by the application of a test to people who are asymptomatic, in order to identify those who probably have the disease and to distinguish them from those who probably do not (UK National Screening Committee, 2003).

4. Cancer screening: Checking for cancer (or for abnormal cells that may become cancer) in people who have no symptoms is called screening (NIH, National Cancer Institute, USA).

5. Substance use disorder: Involves patterns of symptoms caused by using a substance (such as tobacco, alcohol, etc.) that an individual continues taking despite its negative effects.

6. Leukoplakia: A predominantly white plaque of questionable risk having excluded (other) known diseases or disorders that carry no increased risk of cancer (The WHO Collaborating Centre for Oral Cancer Workshop, 2007).

7. Erythroplakia: A predominantly fiery red patch that cannot be characterized clinically or pathologically as any other definable disease (The WHO Collaborating Centre for Oral Cancer Workshop, 2007).

8. Oral lichen planus: An autoimmune chronic inflammatory disease of unknown etiology, characterized by the presence of white reticular lesions and/or erosive and/or atrophic lesions (The WHO Collaborating Centre for Oral Cancer Workshop, 2007).

9. Oral submucous fibrosis: A chronic, insidious disease that affects the oral mucosa resulting in loss of fibro-elasticity of the lamina propria and ultimately fibrosis of the lamina propria and the submucosa with epithelial atrophy (The WHO Collaborating Centre for Oral Cancer Workshop, 2007).