The growing burden of cancer and the required continuum of care are facing inequalities and inequities around the world, and one such example is the rural-urban disparity in cancer [
17]. Rural residence, though a simple variable, encapsulates a complex surrogate for several potential explanatory factors like access to care, lifestyle, environmental exposure, and various socioeconomic factors [
18]. Disparity in cancer outcomes due to rurality is well documented [
3,
14,
19,
20]. Moreover, rapid advances in cancer care will further widen the disparity in outcomes for rural patients without directed effort to understand and address barriers to high-quality care in these regions [
6]. Understanding the context of this disparity will reveal the specific needs of the population [
18], especially for resource-constrained countries like India, which has the largest growing population with a predominantly rural background. Through this paper, we analysed the urban-rural disparity in cancer burden and care for over 6,000 patients in Northern India who were registered under the PBCR of the Varanasi district from the Uttar Pradesh state of India.
Disparities in the socio-cultural distribution
We observed a significant difference in the religion of patients; where compared to the rural patients, who were predominantly Hindu, the urban patients belonged to other religions. Our finding is supported by the Indian Census, which reported that religious minorities tend to migrate and live in urban areas for social security [
25,
26]. On the other hand, the rural patients predominantly spoke the local vernacular language compared to urban patients, who could communicate in the common Hindi language. Language and cultural barriers to cancer treatment and symptom management have been reported among rural patients with cancer [
27]. Patient navigation systems can help overcome this linguistic and cultural barrier [
28].
There was a significant difference in the type of profession among the patients, where the proportion of professionals and semi-professionals was significantly higher in urban patients while farming, un-skilled, semi-, and skilled professions were predominant in rural patients. Previous studies have reported the success of workplace screening in urban populations and community screening in rural populations and future cancer control policies should implement screening strategies accordingly [
29,
30].
The educational and socio-economic status were significantly higher in the urban patients, confirming the prevalent socio-economic disparity in the urban-rural population. Educational and socio-economic status are important factors associated with better health literacy, health-seeking behaviour, screening participation and adherence, early stage at diagnosis, compliance with treatment, and follow-up thereby resulting in an overall better survival of the cancer patients. This disparity in accessing cancer care is further worsened in rural populations because of the large proportion of the uninsured population, high out-of-pocket expenditure, and avoidance of seeking care, as many are daily wagers and face illness-related unemployment and increased travel time to access healthcare facilities [
31].
These socio-demographic factors also influence lifestyle, dietary, behavioural, and environmental factors, as well as healthcare-seeking behaviour and treatment compliance, all of which are decisive entities for cancer survival. It is important to acknowledge urban-rural variability in these factors while designing cancer control programmes. Additionally, realising the spirit of universal health coverage for cancer care is vital to bridge the divide and prevent the resulting impoverishment among already poor and marginalised rural patients with cancer.
Disparities in cancer burden
The overall incidence of cancer in rural areas was lower compared to urban areas, but mortality was higher in rural areas, especially among women. Our findings align with previous national studies. In rural cancer registries (Barshi), the AAIR is nearly one-third of urban PBCRs [
32]. Another study noted that the AAIR in urban Punjab PBCRs (Chandigarh and SAS Nagar) is almost twice that in rural PBCRs (Mansa and Sangrur) [
19]. Similar trends are observed in Nepal, where the urban (Kathmandu) registry showed 1.6 times higher AAR among males and 1.9 times higher AAR among females in comparison to the rural (Rukum) registry [
33]. Conversely, a study in China revealed significantly higher AAIR in rural men, primarily attributed to oesophageal cancer [
14]. Developed countries, like those in North America, consistently reported higher all-site incidence rates in urban populations compared to rural ones [
34].
A complex interplay of rurality with sociodemographic, lifestyle, dietary, behavioural, and environmental factors that affect the screening participation, incidence, and prognosis of the disease is seldom recognised and addressed. Additionally, rural women face several cultural and social barriers, which further aggravate the misery [
3,
35]. This was evident from our findings, where out of the three preventable cancers among women for which screening is recommended in the National programme, two (oral and cervical) had a higher incidence and all three (oral, breast, and cervical) had a higher mortality among rural women. Previous Indian studies have highlighted the inequalities in socioeconomic factors and healthcare utilisation concerning cancer screening in urban and rural populations [
5,
36,
37]. Given the above findings, cancer awareness generation and screening activities must acknowledge the dissimilar socio-demographic background characteristics of urban and rural populations and design strategies accordingly.
Furthermore, various healthcare-related factors such as (i) poor access to cancer treatment facilities, (ii) greater likelihood to receive treatment at smaller hospitals, (iii) lower probability of guideline-concordant treatment practices, (iv) lack of genomic testing and staging, (v) disparity in cancer treatment modalities and quality, (vi) treatment attrition, (vii) significant shortage of specialists, (viii) limited supportive and rehabilitative resources, and (ix) inadequate cancer care navigation are more pronounced in rural regions and contribute to higher mortality [
39,
39]. Healthcare services in urban areas of India generally receive a larger share of public resources, resulting in lower rural health infrastructure investment coupled with issues of ill management, staff absenteeism, and poor capacity-building efforts [
3,
38,
39].
Disparities in the leading cancer sites
We observed a significant difference in the standardised rate ratios for the site-specific cancers for rural and urban patients. Similar observations have been reported from previous cancer registries of India, Nepal, China, and the United States (US) [
14,
19,
33,
40]. The significantly higher AAR for liver cancer in rural patients can be partially attributed to a greater prevalence of alcohol use in the rural Indian population. This is compounded by an earlier age at the onset of alcohol consumption, frequent episodes of heavy drinking, and the consumption of non-brewed alcoholic beverages [
23]. Also, a greater prevalence of hepatitis B infection and a similar prevalence of non-alcoholic fatty liver disease, which are known risk factors for liver cancer, have been reported among rural Indian residents compared to the urban population [
41]. The National Cancer Registry Programme has also reported that liver cancer was highest in the northeastern cancer registries (Papumpasre, West Arunachal, Aizwal, Mizoram) [
11] which have a predominantly rural population (81.64%) [
42] Similarly, China [
14] and US [
43] have also reported higher AAR for liver cancer in their rural populations.
Significantly higher AAR of gallbladder cancer in both male and female rural patients can be partly explained by higher mustard oil consumption, the prevalence of cholelithiasis, chronic typhoid infection, and the consumption of snails, which are often contaminated with liver flukes [
44,
45]. Arsenic in groundwater has recently been linked to gallbladder cancer, and untreated groundwater consumption is more prevalent in rural areas than urban areas, which might further explain the rural predominance of gallbladder cancer [
46]. Several studies from India (cancer registries and case-control studies) have reported rural background as a risk factor for gallbladder cancer [
44,
47]. However, studies from countries such as Nepal [
33] and Chile [
48] have reported urban predominance for gallbladder cancer, which has been explained by the higher prevalence of gallstones, obesity, and hormone use in their urban regions [
33,
48].
We observed significantly higher incidence rates for colon and oesophageal cancer in both men and women with urban backgrounds compared to their rural counterparts. Higher prevalence of obesity, inadequate physical activity, salt and red meat consumption, diabetes, and low consumption of fibre among urban residents could partly decipher the higher incidence rates in the urban population [
49]. Our findings are in line with studies from India that have reported a rising trend in registries established in metropolitan regions (predominantly urban population) such as Delhi, Chennai, Mumbai, and Banglore [
50], and studies from China [
14,
51]. In contrast, studies from the US show a rural preponderance for colon cancer, which has been attributed to higher red meat consumption, obesity, a lack of physical activity, and lower cancer screening adherence in their rural populations [
34,
52]. The urban preponderance of oesophageal cancer observed in our study can be attributed to the increased prevalence of gastroesophageal reflux disease, low fruit and vegetable intake, and obesity, coupled with prevalent tobacco and alcohol use in urban areas [
49,
53]. However, Indian registries from another northern state (Punjab) reported a higher AAR of oesophageal cancer in rural registries (Mansa, Sangrur) in comparison to urban registries (SAS Nagar, Chandigarh) [
19]. In addition, studies from China also reported a higher preponderance of oesophageal cancer in the rural population [
14]. This distinction underscores the heterogeneity in the prevalence of key risk factors, namely tobacco smoking, alcohol consumption, and dietary factors, across intra- and inter-country regions.
We observed that trachea, bronchus, and lung cancer incidence rates were higher in rural patients, which could be explained by indoor air pollution due to biomass burning, exposure to second-hand smoke at home, and tobacco and beedi smoking, which are more prevalent in rural regions of Uttar Pradesh than urban areas [
54,
55]. However, our findings are in contrast with rural registries from other states such as Maharashtra (Barshi) and Punjab (Mansa and Sangrur), which reported lower AAR for lung cancer, and urban registries (Chandigarh, SS Nagar, Trivandrum, Chennai, and Delhi), which reported higher incident rates [
18,
54]. In addition, several urban registries from eastern African countries (Malawi, Zimbabwe, Uganda, and Kenya) have also reported a high burden of lung cancer [
56]. Our finding is in line with registries from Korea [
57], China [
14], and the US [
34], which reported rural predispositions for lung cancer incidence. These diverse observations underscore how various factors, including smoking, indoor and outdoor air pollution, and the utilization of lung cancer screening, interact in different contexts, leading to the urban-rural disparity in lung cancer incidence.
Both penile cancer in men and cervical cancer in women share some of the risk factors, including infection with the Human Papilloma Virus, increasing age, poor hygiene, tobacco use, multiple sexual partners, low education, and socio-economic status. Most of these factors are predominant in rural areas, thereby explaining the high rates of these cancers in rural patients in our study [
58,
59]. Cervical cancer predominance in rural women has been unanimously reported in several registry studies from India [
19,
60], Nepal [
33], Sub-Saharan Africa [
61], China [
51] and the US [
62]. Despite a lower incidence of prostate cancer, rural men had almost similar cancer-related mortality as urban patients, which is worrisome and could be due to a wide urban-rural gap in screening as well as treatment facilities and modalities. Previous Indian research has shown lower screening rates among rural patients, and rural patients with prostate cancer are less likely to receive definitive treatment than their urban counterparts [
63‐
65]. Systematic reviews, which mostly used data from high-income countries, showed that rural-urban differences in prostate cancer incidence and mortality were confirmed. It was found that while incidence was higher in urban men, mortality was higher in rural men. This was partly because of the systemic barriers that made it take longer for men to get diagnosed and treated for prostate cancer [
66,
67].
A negative rural-urban risk difference in the incidence of endometrial, breast, and ovarian cancer can be attributed to a relatively greater prevalence of risk factors like obesity, metabolic syndrome, nulli-and-low parity, late pregnancy, infertility, use of hormones, early age at menarche, and poor lifestyles like inadequate physical activity, a high-fat diet, and alcohol and tobacco use in urban areas than in rural regions [
68]. Our findings are in line with the observations from other Indian PBCRs where breast cancer was the leading cancer in registries of urban agglomerations [
19] and cervix cancer was the leading cancer in rural registries like Barshi, Mizoram, Tripura, Pasigat, Nagaland, Cachar, Osmanabad, and Beed [
68]. The urban preponderance of these women’s cancers associated with a hormonal etiology has been reported in several studies from Nepal [
33], Egypt [
69], China [
70], and the US [
34].
We observed that, despite significantly lower breast cancer incidence in rural women, higher mortality was observed in them compared to their urban counterparts. This signifies the rural-urban disparities in the early detection of breast cancer, delayed care seeking, and treatment initiation. Previous Indian studies reported that rural women are less likely to get screened and more likely to present at late stages of breast cancer compared to their urban counterparts [
35,
71]. Furthermore, the significantly higher incidence of breast, endometrial, ovarian, and colon cancers in urban female patients hints towards further research for understanding the genetic predisposition and genetic screening and counselling.
We observed that mouth cancer was the predominant cancer in our study population. Surprisingly, despite well-documented higher tobacco use in rural parts of India and Uttar Pradesh [
21,
22], we observed a statistically significant higher incidence and mortality of mouth cancer in urban men. Previous studies comparing the incidence rates of oral cancer have also shown significantly higher incidence in urban PBCRs compared to rural PBCRs [
72]. Additionally, analysis of a national representative survey also reported higher rates of tobacco-related cancer deaths in urban than rural men [
35]. This can be explained to a certain extent by several factors. Firstly, poor cancer screening coverage was reported in the national survey [
63] where the oral cancer screening rates were lower in the rural population, thus reflecting the impact of poor screening coverage on the cancer incidence distribution. The second explanation can be the significantly higher proportion of the elderly in our urban study population, and as discussed previously, age itself is an important independent risk factor for carcinogenesis. Thirdly, studies from India have reported that most of the oral cancers detected in rural populations are in advanced stages with poor 5-year survival [
38,
73]. Previously, a review on oral cancer burden in India reported variations in the AAR of oral cancer in rural men across many registries. One explanation cited was the lack of transportation, which hinders seeking diagnosis and care in rural populations [
73]. Therefore, this contradicting finding from our study underscores the rural-urban disparity in the early detection of oral cancer in this region. Registry from China [
14] reported higher AAR in urban men while the North American Registries [
34] reported higher incidence in rural men, and both attributed this difference to the higher tobacco consumption in their urban and rural populations, respectively.