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Prevalence of oral human papillomavirus infection among Indian HIV-positive men who have sex with men: a cross-sectional study

Abstract

Background

Oral human papillomavirus (HPV) infection has been causally linked to a subset of oropharyngeal cancers in Western populations, and both oropharyngeal cancer and oral HPV infection are increased among HIV-positive individuals. India has high incidences of oral and oropharyngeal cancers, and Indian HIV-positive men who have sex with men (MSM) may be at increased risk of developing oropharyngeal cancers. However, there is little information available on the prevalence of oral HPV in this population.

Methods

We tested 302 HIV-positive Indian MSM for oral HPV infection using L1 HPV DNA PCR with probes specific for 29 types and a mixture of 10 additional types. CD4+ level and plasma HIV viral load (VL) were measured. Participants completed an interviewer-administered questionnaire including a sexual history.

Results

The prevalence of oral HPV was 23.7% (95% CI: 19–29%) and 2.4% of participants had oncogenic HPV types. No participants had oral HPV type 16 (HPV-16) and the prevalence of other anogenital HPV types was low. Participants with higher CD4+ levels had reduced odds of having any oral HPV infection (OR: 3.1 [1.4–6.9]) in multivariable analyses.

Conclusions

This is the first report of oral HPV among Indian HIV-positive MSM. Our results show a high prevalence of oral HPV infection consistent with studies from Western populations. However, oncogenic anogenital HPV types were relatively uncommon in our study population. It is unknown what the impact of this distribution of oral HPV will be on oropharyngeal cancers. HIV-positive MSM in India should be monitored closely for oral and oropharyngeal pre-cancer and cancer.

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Introduction

The incidence of oral squamous cell carcinoma (OSCC) is higher in India than in western countries. In India, there are an estimated 12.6–20.0 per 100,000 new cases of OSCC each year [1, 2]. OSCCs comprise 40–50% of all malignancies diagnosed in India and they are the most common cancer among Indian men [3]. This is in contrast to the global prevalence where oral cancers comprise only 2–4% of all cancers, and to the United States where cancers of the oral cavity and pharynx account for only 3% of all new cancer cases [4,5,6,7,8,9]. The difference in occurrence has largely been attributed to the high prevalence of established risk factors for OSCC, primarily the use of tobacco products and heavy alcohol consumption [10]. India has an additional lifestyle behavior that has been linked to oral cancers, i.e., the practice of chewing ‘betel quid’ (a combination of betel leaf, smokeless tobacco, areca nut, and lime paste). In addition to the established carcinogenicity of the smokeless tobacco in betel quid, areca nut (alone and in combination with the lime paste) is thought to be an oral carcinogen [11,12,13].

There is established epidemiological and molecular evidence that human papillomavirus (HPV) is causally associated with a subset of OSCCs, oropharyngeal cancer, and particularly with cancers of the palatine and lingual tonsils [14,15,16,17,18,19]. The prevalence of HPV DNA detected in OSCC varies broadly by DNA detection techniques, population, type of cancer specimen, and anatomical location of the cancer. Worldwide, the prevalence of HPV DNA reported for OSCC is between 11 and 48% [14, 20, 21]. However, HPV is consistently and most frequently detected in cancers of the lingual and palatine tonsils of the oropharynx (12–63%) in studies conducted in the West [17, 22, 23]. HPV-16 is the most common HPV type and accounts for almost 90% of HPV associated OSCCs [16, 24, 25]. Other HPV types found in OSCC include HPV-18, HPV-33, and HPV-35 [16, 24, 25]. Studies conducted in India on HPV in OSCCs show the same variability in estimates as do Western studies (25–100%) [13, 26,27,28,29,30,31,32,33]. Currently, there are few data available on oral HPV infection in individuals without OSCC in India.

HIV infection is associated with increased risk of both OSCC and oral HPV infection in western countries. It is well established that HIV-positive individuals have an elevated risk for HPV-associated cancers including cervical and anal cancers [34]. Similarly, HIV-positive individuals have two to four times the risk of developing OSCC and two to six times the risk of developing oropharyngeal cancer compared with HIV-negative individuals [23]. The incidence of oropharyngeal cancer has not decreased and may be increasing since the advent of antiretroviral medications [35, 36], a relationship that has also been noted with cervical and anal cancers [37]. Also, in western countries, oral HPV infection (as well as anogenital HPV infection) is more common among individuals with HIV infection [38, 39]. HIV-positive individuals have two to three times the risk of oral HPV infection compared with HIV-negative individuals [40] and the prevalence of oral HPV infection has been shown to increase with decreasing CD4+ levels [41]. A recent meta-analysis reported the pooled prevalence of any HPV infection among HIV-positive MSM was 28.9 and 4.7% for HPV-16 [42].

India has approximately 2.14 million individuals living with HIV/AIDS, with Indian MSM having some of the highest prevalence estimates of HIV infection (6–68%) [3, 43, 44]. This confluence of risk factors, including the high background incidence of OSCCs; HIV and HPV infections; and the use of tobacco, alcohol, and betel quid, potentially puts Indian MSM at a uniquely high risk of OSCC. We have also previously reported that this population has a very high prevalence of anal HPV infection [45] and a high prevalence of penile HPV infection [46]. However, there are no studies yet reported on the occurrence of oral HPV infection among Indian HIV-positive men, including MSM. Given that HPV infection is potentially preventable though behavioral modification or vaccination [18, 47], it can be reasoned that a portion of OSCCs may also be preventable. Determining the prevalence of oral HPV infection is an important first step in developing prevention interventions for this high-risk group in India, as well as prevention interventions for HIV-positive individuals worldwide. Therefore, we conducted a cross-sectional study in two cities in India to determine the prevalence and risk factors for oral HPV infection among Indian HIV-positive MSM.

Materials and methods

HIV-positive MSM were recruited from two study sites, Christian Medical College (CMC), Vellore, Tamil Nadu (a large research and teaching institution) and Humsafar Trust (HT), Mumbai (a male sexual health non-governmental organization [NGO]). Men were recruited through outreach workers, local HIV/AIDS support groups, and were also referred from other NGOs. Enrollment occurred from September 2009 to August 2010. Men were eligible for the study if they had had sexual contact with another male in the preceding 6 months, were HIV-positive, and were at least 18 years of age. Participants were asked to rinse and gargle with 10 ml of Scope™ for 30 seconds and expectorate into a 50 ml wide-mouth sterile tube to collect oral cells for HPV testing as described previously [48]. Participants completed a questionnaire in the local language administered by a male interviewer. The English language version of the questionnaire is included as Supplemental File 1. The participants had a clinical examination, including collection of anal and penile specimens for HPV testing. Blood was collected for a CD4+ lymphocyte count measured by standardized two- or three-color fluorescence methods. Plasma HIV viral load (HIV VL) was measured using the Amplicor HIV Monitor test, Version 1.5 (Roche, USA). All procedures were performed after obtaining written informed consent from participants. The study was approved by the Committee on Human Research of UCSF, and the Institutional Review Boards of both CMC and HT.

Testing for oral, penile and anal HPV DNA was performed as described previously using the polymerase chain reaction (PCR) with L1 consensus primers and probes specific for 29 individual HPV types and a mixture of 10 additional types (using a combined probe) for a total of 39 HPV types [49]. Beta-globin-negative samples (indicating insufficient good quality DNA) were excluded from analysis. We defined infection with an oncogenic HPV type as a positive test for at least one of the following types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 [50]. Results for penile and anal HPV infections were published separately [51, 52].

Assessment of potential risk factors

Demographic factors, medical history, use of antiretroviral therapy (ART) and history of sexual behavior were collected. We asked the participants if they had smoked more than 100 cigarettes in their lifetime (yes/no). They were asked if they ‘regularly’ chewed smokeless tobacco, and if so how much they used (‘regularly’ was not defined for participants, but was translated into Hindi and Tamil, with the back translation of roughly “regularly” or “often”). We also asked men if they had ever consumed alcoholic beverages. We asked about sexual behaviors over the participant’s lifetime. Men were queried about multiple types of sexual behaviors, including sex with men and women, oral sex with women (participant’s mouth in contact with woman’s vulva/vagina), oral sex with men (participant’s mouth in contact with man’s penis), oral-anal contact (“rimming”, participant’s mouth in contact with partner’s anus), “insertive” anal intercourse (participant inserts his penis into partner’s anus), “receptive” anal intercourse (participant receives his partner’s penis into his anus), and vaginal sex.

Statistical analysis

Prevalence was calculated as the total number of participants with a positive consensus probe for oral HPV infection divided by the total number of participants positive for beta-globin (multiplied by 100). Exact binomial 95% confidence intervals (CIs) were calculated for each prevalence estimate. We chose to examine bivariable association with factors that had been shown in previous reported studies to be associated with oral cancer, oral HPV infection, or other HPV infections or HPV-associated cancers. We assessed bivariable associations with any oral HPV infection and socio-demographic, clinical and lifestyle characteristics using the chi-square test for categorical variables and analysis of variance (ANOVA) or ranked ANOVAs for continuous variables, as appropriate.

Odds ratios (ORs) were derived from unadjusted logistic regression models. We evaluated confounding between select risk factors that showed significance in bivariable analyses and oral HPV infection by adding covariates to our unadjusted model to construct four additional adjusted models. The first adjusted model contained the select risk factor and the CD4+ level. The second adjusted model contained the risk factor plus the demographic factors age, marital status, and income. The third adjusted model included the risk factor plus the lifetime number of vaginal sex partners. The last adjusted model included the risk factor plus the lifetime number of male partners with whom the participant was the receptive partner during anal intercourse. Potential confounding was considered to be present if the OR on the select risk factor changed by 10% or greater with the addition of the covariable(s) into the model.

Lastly, we constructed a final multivariable model that included variables with a p-value of < 0.10 in bivariable analyses, plus any variables which demonstrated confounding. Variables were considered significantly associated with oral HPV infection if the p was < 0.05 (no adjustment was made for multiple comparisons). All analyses were conducted separately by two analysists (ALH and SL) in SAS 9.4 (SAS North Carolina).

Results

We enrolled 302 HIV-positive Indian MSM and of these, 7 (2%) had beta-globin-negative samples and were excluded from further analysis. Of the 295 remaining participants, the median age was 34 years, the median monthly income was 3000 rupees (approximately $50), and most (65%) had 1–10 years of education. Participants from our two clinical sites were different demographically. Men from Humsafar Trust were younger (38 vs. 32 years), a greater proportion had completed more than 10 years of school (27% vs 9%), they had a higher median income (6000 INR vs. 2000 INR), and more reported their religion as being “Muslim” (24% vs. 3%) (all comparisons p ≤ 0.05).

Almost half of our participants reported being married to a woman (47%). Only 30% of men reported that they have ever smoked 100 or more cigarettes, and only 31% reporting chewing tobacco ‘regularly’. More than half of our participants reported consuming alcoholic beverages in their lifetime, but 46% drank less than 1 day per week.

The median CD4+ level of the study population was 424 cells/uL (interquartile range [IQR]: 273–581 cells/uL) and the median HIV VL was 8307 IU/mL (IQR: ≤400–79,400 IU/mL) 36% had undetectable levels. Forty-eight percent of participants were taking antiretroviral therapy (ART) and of those 69% of participants had been taking ART for more than a year. Men from the two different sites did not differ significantly in their lifestyle behaviors or HIV disease status.

Prevalence of oral HPV infection

The prevalence of oral HPV infection among our participants was 23.7% (95% CI: 19–29%) (Table 1). Three percent of participants had oral infection with oncogenic HPV types. Of the 70 men with positive consensus probes for oral HPV infection, only 17 had positive results on HPV type-specific tests included in our testing. Of the 17 who had HPV type-specific results, 14 (82%) had more than one type of HPV detectable. Oral HPV 16 infection was not detected in any of our participants. The prevalence of oral HPV infection did not differ by study location.

Table 1 Type-specific prevalence of oral HPV infection among HIV-positive Indian MSM

Unadjusted associations between demographic factors, lifestyle factors, HIV-related factors and oral HPV infection

There was no significant association between any of the demographic factors examined and oral HPV infection (Table 2). Of the lifestyle factors investigated, two factors commonly associated with OSCC, cigarette smoking and alcohol consumption, were not associated with oral HPV infection in this population. However, chewing tobacco ‘regularly’ was associated with lower prevalence of oral HPV infection among HIV-positive MSM (14%) compared with men who did not chew tobacco (28%) (p = 0.01, OR 0.4 [95% CI 0.2–0.8]). However, among the 93 men who did chew tobacco regularly, when we examined the frequency that they chewed tobacco by week, the prevalence of oral HPV infection increased with increasing frequency of weekly chewing tobacco use.

Table 2 Socio-demographic factors, medical history and oral HPV infection among Indian HIV-positive MSM (N = 295)

Men with lower CD4+ levels had a higher prevalence of oral HPV infection when compared with men with higher CD4+ levels (500+ cells/uL). Men with < 200 cells/uL had a prevalence of 43% and men with 500+ cells/uL had a prevalence of 20% (p = 0.01). HIV VL and ART use were not associated with oral HPV infection.

Sexual behavior and oral HPV infection

Several oral sexual behaviors were associated with a reduction in prevalence of oral HPV infection among our participants (Table 3). Men who reported having performed oral sex on a woman in their lifetime had a lower prevalence of oral HPV compared with men who reported never performing oral sex on a woman (17% vs. 32%, p = 0.02). However, among those reporting that they had performed oral sex on a woman, the prevalence of oral HPV increased with increasing number of partners on whom the participant had performed oral sex. Engaging in oral-anal contact (rimming), showed a similar association with a lower prevalence among those who engaged in this behavior. Ever performing genital oral sex on a male partner was not associated with oral HPV infection. Behaviors that measured non-oral sexual contact with other partners were not associated with oral HPV infection including vaginal sex, total number of male partners, insertive anal intercourse with men, or receptive anal intercourse with men.

Table 3 Sexual history and oral HPV infection among Indian HIV-positive MSM

Evaluation of confounding of select risk factors

We evaluated potential confounding between three risk factors and oral HPV infection (Table 4). We found no evidence of confounding with any of the variables examined in the association between performing oral sex on a woman and engaging in oral-anal contact and oral HPV infection. The addition of vaginal sex to the model with chewing tobacco regularly strengthened the association. None of the potential confounding factors examined in this analysis nullified the associations between the chewing tobacco and oral HPV infection or performing oral sex on a woman and oral HPV infection, and all of the 95% CIs continued to exclude the null value of 1.0.

Table 4 Potential confounding of the relationship between select risk factors and oral HPV infection among HIV-positive Indian MSM

Multivariable adjusted associations with oral HPV infection

We included each variable that was significant in bivariable analyses in a multivariable model along with the variables that were diagnosed as potential confounders (Table 5). In this model, CD4+ level continued to show an association with oral HPV when < 200 cells/uL compared with 500+ (OR: 2.9 [95% CI 1.0–9.1]). Reporting chewing tobacco ‘regularly’ also continued to show a protective effect (OR: 0.2 [95% CI 0.1–0.6]) in adjusted analyses as did performing oral sex on a woman (OR: 0.4 [95% CI 0.2–0.9]). When adjusted for the other factors, engaging in oral-anal contact was no longer significantly associated with oral HPV infection. While not significant in bivariable analyses, when the number of vaginal sex partners was included in the multivariable model, having 1–4 vaginal sex partners increased the odds of having oral HPV infection (OR: 2.7 [95% CI 1.1–6.5]), although the comparisons between having no partners, having 5–39 partners, and having 40+ partners were not significantly associated with oral HPV infection.

Table 5 Multivariable adjusted associations with oral HPV infection among HIV-positive Indian MSM

Discussion

This is the first report of the prevalence of oral HPV infection among Indian HIV-positive MSM. Our participants had a similar prevalence of any oral HPV infection compared with other HIV-positive populations, with previous estimates ranging from 14 to 45% [40, 41, 53]. However, unlike other reports of oral HPV among HIV-positive MSM, our participants had fewer oncogenic HPV types that are typically found in the anogenital tract. Only 6% of our participants had one of the 39 types for which we tested, only 2.4% had an oncogenic anogenital HPV type and none had HPV 16. Previous studies have found a prevalence between 11 and 20% of oncogenic HPV types and 7–10% HPV 16 in their study populations [40, 53]. Using the same HPV detection methods, our study population had high levels of penile (48%) [52] and anal (95%) [51] HPV infection, comparable to other populations of HIV-infected MSM. These same methods were also used in a recent study of oral HPV infection among MSM in San Francisco that reported a 30% prevalence of oral HPV with an 11% prevalence of oncogenic HPV types [54].

Although no studies of oral cancer among HIV-positve men in India have occurred to date, studies of HIV-negative men and women indicate that HPV does play a role in Indian oral and oropharyngeal cancers in India. The prevalence of HPV-16, for example, in biopsies of oral and oropharyngeal cancers of Indian HIV-negative men and women ranges from 0% [55, 56] to over 30% [13, 33, 57, 58] showing that oral HPV-16 infection may be important in Indian oral cancers as it is in other populations. However, the association between HPV and oral cancers has not been as well characterized in India as in other countries and the prevalence of other risk factors for oral cancers in India is high.

Another difference between our results and previously reported results was that individuals who reported chewing tobacco regularly had a lower prevalence of oral HPV infection than those who reported that they did not regularly chew tobacco and this association remained significant in multivariable adjusted analyses. Chewing tobacco has not been associated with oral HPV infection in previous studies, however it has been consistently associated with oral cancers [59, 60] and oral pre-cancerous lesions [61, 62]. Several studies have described two separate pathways to oral and oropharyngeal cancers; one that includes tobacco products and another that includes oral HPV infection [23, 63,64,65,66]. Studies that have examined effect modification between tobacco products and oral HPV have had conflicting results [67, 68]. It is possible that while chewing tobacco is associated with cancers of the oral cavity, it is not associated with cancers that are associated with HPV infection. The mechanism of protection provided by chewing tobacco in this case is not clear. It may be that the smokeless tobacco itself or another component in the chewing tobacco mixture may interfere with oral HPV infection. Also, in our study we did not clarify a difference between chewing tobacco and chewing betel quid (areca nut). Indian betel quid, a combination of betel leaf, smokeless tobacco, areca nut and lime paste (a mixture of calcium and hydroxide-calcium carbonate), has itself been associated with oral cancers [11,12,13]. It is possible, however, that one of the components of betel quid interferes with oral HPV infection. Finally, we cannot exclude the possibility that one or more components of chewing tobacco in the oral specimens interfered with detection of HPV DNA in our typing assay.

Two other factors showed protective effects in our analyses that were different from what has been shown in the literature [69], i.e. oral-anal contact (rimming) and having oral sex with women. These associations did not dissipate when adjusted for marital status, number of female vaginal sex partners or number of oral sex partners. However, in our fully adjusted model (that included both chewing tobacco and oral sex with women), oral-anal contact was no longer significant. We found a limited number of anogenital HPV types in our oral samples in our study and sexual risk factors may not be as important in this population. This implies that non-sexual routes of exposure may be more significant to the development of oral HPV infection than sexual ones in this population. Although this does not explain the protective effect we found with oral-anal contact and oral sex with women, it may explain why they were not found to be risk factors. It may be that that these sexual behaviors are markers of behaviors that participants do not engage in, or engage in less often. Focus group discussions and key informant interviews should precede any future study on oral HPV infection with HIV-positive MSM in India.

In contrast to the behavioral data, the results collected with a biological markers of HIV disease status were consistent with data from Western populations. Among our study participants, having a lower CD4+ level was associated with a higher prevalence of oral HPV infection. Studies of Western HIV-positive MSM have also found that lower CD4+ level was associated with higher risk of oral HPV infection in men [40, 41] and a number of studies have also seen this association among HIV-positive women [41, 48]. This is also consistent with the relationship seen with anal and cervical HPV infection where lower CD4+ levels are associated with increased incidence and prevalence of HPV infection and HPV-associated disease [49, 51, 70,71,72,73,74].

Our study had a few limitations. It was designed as a cross-sectional study because it was the first study of oral HPV among HIV-positive men in India. Additionally, we did not have a random sample of Indian HIV-positive MSM and the results may not be generalizable to all HIV-positive Indian MSM but only Indian MSM living in urban centers with access to medical services. However, MSM behavior and HIV-positive status are both highly stigmatized in India, and it is unlikely that other sampling strategies would have yielded a more representative sample while ensuring participant confidentiality.

Conclusion

Although our study has confirmed that Indian HIV-positive MSM have a similar prevalence of oral HPV infection as in previous reports from other parts of the world, they have fewer anogenital HPV types, particularly oncogenic HPV types, detectable in the mouth. This is in stark contrast to what we found for penile [52] and anal HPV infection [51] in this same population which had very similar distribution of oncogenic anogenital HPV types to other HIV-positive populations in other locations. Indian HIV-positive MSM also differ from Western MSM in lifestyle, sexual history, and cultural practices and thus may have different risk factors for oral HPV infection than they do for penile and anal HPV infections. Although oral and oropharyngeal cancer are very important in India, oral HPV infection may not be as important in this population as it is in previously studied populations. Studies of oral cancer among HIV-positive men would help elucidate the role of HPV in oral and oropharyngeal cancers in India.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ANOVA:

Analysis of variance

ART:

Antiretroviral therapy

CD4:

Cluster of differentiation 4

CI:

Confidence interval

CMC:

Christian Medical College, Vellore, India

DNA:

Deoxyribonucleic acid

HIV/AIDS:

Human immunodeficiency virus/acquired immunodeficiency syndrome

HPV:

Human papillomavirus

HT:

Humsafar Trust, Mumbai, India

L1:

Major capsid protein

NGO:

Non-governmental organization

MSM:

Men who have sex with men

OR:

Odds ratios

OSCC:

Oral squamous cell carcinoma

PCR:

Polymerase chain reaction

VL:

Viral load

References

  1. 1.

    Petersen PE. Strengthening the prevention of oral cancer: the WHO perspective. Community Dent Oral Epidemiol. 2005;33(6):397–9.

    Article  Google Scholar 

  2. 2.

    Coelho KR. Challenges of the oral cancer burden in India. J Cancer Epidemiol. 2012;2012:701932.

    Article  Google Scholar 

  3. 3.

    National AIDS Control Organisation (NACO). Department of AIDS Control Ministry of Health and Family Welfare. New Delhi; National AIDS Control Organization; 2010. http://www.nacoonline.org.

  4. 4.

    Ferlay J, Bray F, Pisani P, Parkin A. Globocan 2000-cancer incidence mortality and prevalence worldwide, version 1.0. Lyon: IARC; 2001.

    Google Scholar 

  5. 5.

    Chocolatewala NM, Chaturvedi P. Role of human papilloma virus in the oral carcinogenesis: an Indian perspective. J Cancer Res Ther. 2009;5(2):71–7. https://doi.org/10.4103/0973-1482.52788.

  6. 6.

    Markopoulos AK. Current aspects on oral squamous cell carcinoma. Open Dent J. 2012;6(1):126–30. https://doi.org/10.2174/1874210601206010126.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American Cancer Society; 2016. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2016.html.

  8. 8.

    Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol. 2001;2(9):533–43. https://doi.org/10.1016/S1470-2045(01)00486-7.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94(2):153–6. https://doi.org/10.1002/ijc.1440.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Döbrossy L. Epidemiology of head and neck cancer: magnitude of the problem. Cancer Metastasis Rev. 2005;24(1):9–17. https://doi.org/10.1007/s10555-005-5044-4.

    Article  PubMed  Google Scholar 

  11. 11.

    Sankaranarayanan R, Duffy SW, Day NE, Nair MK, Padmakumary G. A case-control investigation of cancer of the oral tongue and the floor of the mouth in southern India. Int J Cancer. 1989;44(4):617–21. https://doi.org/10.1002/ijc.2910440410.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Sankaranarayanan R, Duffy S, Padmakumary G, Day N, Padmanabhan T. Tobacco chewing, alcohol and nasal snuff in cancer of the gingiva in Kerala, India. Br J Cancer. 1989;60(4):638–43. https://doi.org/10.1038/bjc.1989.330.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Nair UJ, Nair J, Mathew B, Bartsch H. Glutathione S-transferase M1 and T1 null genotypes as risk factors for oral leukoplakia in ethnic Indian betel quid/tobacco chewers. Carcinogenesis. 1999;20(5):743–8. https://doi.org/10.1093/carcin/20.5.743.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Gillison ML. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92(9):709–20. https://doi.org/10.1093/jnci/92.9.709.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Syrjänen KJ, Syrjänen SM, Lamberg MA, Pyrhönen S. Human papillomavirus (HPV) involvement in squamous cell lesions of the oral cavity. Proc Finn Dent Soc. 1983;79(1):1–8.

    PubMed  Google Scholar 

  16. 16.

    Nair S, Pillai M. Human papillomavirus and disease mechanisms: relevance to oral and cervical cancers*. Oral Dis. 2005;11(6):350–9. https://doi.org/10.1111/j.1601-0825.2005.01127.x.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Herrero R. Chapter 7: human papillomavirus and Cancer of the upper Aerodigestive tract. JNCI Monogr. 2003;2003(31):47–51. https://doi.org/10.1093/oxfordjournals.jncimonographs.a003482.

    Article  Google Scholar 

  18. 18.

    Guo T, Eisele DW, Fakhry C. The potential impact of prophylactic human papillomavirus vaccination on oropharyngeal cancer. Cancer. 2016;122(15):2313–23. https://doi.org/10.1002/cncr.29992.

    Article  PubMed  Google Scholar 

  19. 19.

    Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of human papillomavirus–positive head and neck squamous cell carcinoma. J Clin Oncol. 2015;33(29):3235–42. https://doi.org/10.1200/JCO.2015.61.6995.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Mehanna H, Beech T, Nicholson T, El-Hariry I, McConkey C, Paleri V, et al. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer-systematic review and meta-analysis of trends by time and region. Eisele DW, editor. Head Neck. 2013;35(5):747–55.

    Article  Google Scholar 

  21. 21.

    Saulle R, Semyonov L, Mannocci A, Careri A, Saburri F, Ottolenghi L, et al. Human papillomavirus and cancerous diseases of the head and neck: a systematic review and meta-analysis. Oral Dis. 2015;21(4):417–31. https://doi.org/10.1111/odi.12269.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Kreimer AR. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14(2):467–75. https://doi.org/10.1158/1055-9965.EPI-04-0551.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Gillison ML. Oropharyngeal cancer: a potential consequence of concomitant HPV and HIV infection. Curr Opin Oncol. 2009;21(5):439–44. https://doi.org/10.1097/CCO.0b013e32832f3e1b.

    Article  PubMed  Google Scholar 

  24. 24.

    Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. JNCI J Natl Cancer Inst. 2008;100(4):261–9. https://doi.org/10.1093/jnci/djn011.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal Cancer incidence in the United States. J Clin Oncol. 2011;29(32):4294–301. https://doi.org/10.1200/JCO.2011.36.4596.

    Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Jalouli J, Ibrahim SO, Mehrotra R, Jalouli MM, Sapkota D, Larsson P-A, et al. Prevalence of viral (HPV, EBV, HSV) infections in oral submucous fibrosis and oral cancer from India. Acta Otolaryngol. 2010;130(11):1306–11. https://doi.org/10.3109/00016481003782041.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Gheit T, Vaccarella S, Schmitt M, Pawlita M, Franceschi S, Sankaranarayanan R, et al. Prevalence of human papillomavirus types in cervical and oral cancers in Central India. Vaccine. 2009;27(5):636–9. https://doi.org/10.1016/j.vaccine.2008.11.041.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Jamaly S, Khanehkenari MR, Rao R, Patil G, Thakur S, Ramaswamy P, et al. Relationship between p53 overexpression, human papillomavirus infection, and lifestyle in Indian patients with head and neck cancers. Tumor Biol. 2012;33(2):543–50. https://doi.org/10.1007/s13277-011-0295-x.

    CAS  Article  Google Scholar 

  29. 29.

    Koppikar P, DeVilliers E-M, Mulherkar R. Identification of human papillomaviruses in tumors of the oral cavity in an Indian community. Int J Cancer. 2005;113(6):946–50. https://doi.org/10.1002/ijc.20664.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Mitra S, Banerjee S, Misra C, Singh RK, Roy A, Sengupta A, et al. Interplay between human papilloma virus infection and p53 gene alterations in head and neck squamous cell carcinoma of an Indian patient population. J Clin Pathol. 2006;60(9):1040–7. https://doi.org/10.1136/jcp.2005.034835.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Saranath D, Tandle AT, Teni TR, Dedhia PM, Borges AM, Parikh D, et al. p53 inactivation in chewing tobacco-induced oral cancers and leukoplakias from India. Oral Oncol. 1999;35(3):242–50. https://doi.org/10.1016/S1368-8375(98)00110-9.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Barwad A, Sood S, Gupta N, Rajwanshi A, Panda N, Srinivasan R. Human papilloma virus associated head and neck cancer: a PCR based study. Diagn Cytopathol. 2012;40(10):893–7. https://doi.org/10.1002/dc.21667.

    Article  PubMed  Google Scholar 

  33. 33.

    Kulkarni SS, Kulkarni SS, Vastrad PP, Kulkarni BB, Markande AR, Kadakol GS, et al. Prevalence and distribution of high risk human papillomavirus (HPV) types 16 and 18 in carcinoma of cervix, saliva of patients with oral squamous cell carcinoma and in the general population in Karnataka, India. Asian Pac J Cancer Prev. 2011;12(3):645–8.

    PubMed  Google Scholar 

  34. 34.

    Palefsky J. Human papillomavirus-related disease in people with HIV. Curr Opin HIV AIDS. 2009;4(1):52–6. https://doi.org/10.1097/COH.0b013e32831a7246.

    Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Clifford GM, Polesel J, Rickenbach M, Dal Maso L, Keiser O, Kofler A, et al. Cancer risk in the Swiss HIV cohort study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. JNCI J Natl Cancer Inst. 2005;97(6):425–32. https://doi.org/10.1093/jnci/dji072.

    Article  PubMed  Google Scholar 

  36. 36.

    Powles T, Robinson D, Stebbing J, Shamash J, Nelson M, Gazzard B, et al. Highly active antiretroviral therapy and the incidence of non–AIDS-defining cancers in people with HIV infection. J Clin Oncol. 2009;27(6):884–90. https://doi.org/10.1200/JCO.2008.19.6626.

    Article  PubMed  Google Scholar 

  37. 37.

    Long JL, Engels EA, Moore RD, Gebo KA. Incidence and outcomes of malignancy in the HAART era in an urban cohort of HIV-infected individuals. AIDS. 2008;22(4):489–96. https://doi.org/10.1097/QAD.0b013e3282f47082.

    Article  PubMed  Google Scholar 

  38. 38.

    Fakhry C, Gillison ML. Clinical implications of human papillomavirus in head and neck cancers. J Clin Oncol. 2006;24(17):2606–11. https://doi.org/10.1200/JCO.2006.06.1291.

    Article  PubMed  Google Scholar 

  39. 39.

    Cameron JE, Mercante D, O’Brien M, Gaffga AM, Leigh JE, Fidel PL, et al. The Impact of highly active antiretroviral therapy and immunodeficiency on human papillomavirus infection of the Oral cavity of human immunodeficiency virus seropositive adults. Sex Transm Dis. 2005;32(11):703–9. https://doi.org/10.1097/01.olq.0000175398.34610.2e.

    Article  PubMed  Google Scholar 

  40. 40.

    Beachler DC, Weber KM, Margolick JB, Strickler HD, Cranston RD, Burk RD, et al. Risk factors for Oral HPV infection among a high prevalence population of HIV-positive and at-risk HIV-negative adults. Cancer Epidemiol Biomarkers Prev. 2012;21(1):122–33. https://doi.org/10.1158/1055-9965.EPI-11-0734.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Kreimer AR, Alberg AJ, Daniel R, Gravitt PE, Viscidi R, Garrett ES, et al. Oral human papillomavirus infection in adults is associated with sexual behavior and HIV Serostatus. J Infect Dis. 2004;189(4):686–98. https://doi.org/10.1086/381504.

    Article  PubMed  Google Scholar 

  42. 42.

    King EM, Oomeer S, Gilson R, Copas A, Beddows S, Soldan K, et al. Oral Human Papillomavirus Infection in Men Who Have Sex with Men: A Systematic Review and Meta-Analysis. Lama JR, editor. PLoS One. 2016;11(7):e0157976.

    Article  Google Scholar 

  43. 43.

    Jerajani H, Kumta S, Ekstrand M, Mathur M, Gogate A, Kavi A, et al. Men who have sex with men and transgenders in Mumbai, India: An emerging risk group for STIs and HIV. Indian J Dermatol Venereol Leprol. 2006;72(6):425.

    Article  Google Scholar 

  44. 44.

    Solomon SS, Srikrishnan AK, Sifakis F, Mehta SH, Vasudevan CK, Balakrishnan P, et al. The emerging HIV epidemic among men who have sex with men in Tamil Nadu, India: geographic diffusion and bisexual concurrency. AIDS Behav. 2010;14(5):1001–10. https://doi.org/10.1007/s10461-010-9711-2.

    Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Hernandez AL, Karthik R, Sivasubramanian M, Raghavendran A, Gnanamony M, Lensing S, et al. Prevalence of anal HPV infection among HIV-positive men who have sex with men in India. JAIDS J Acquir Immune Defic Syndr. 2016;71(4):437–43. https://doi.org/10.1097/QAI.0000000000000855.

    Article  PubMed  Google Scholar 

  46. 46.

    Raghavendran A, Hernandez AL, Lensing S, Gnanamony M, Karthik R, Sivasubramanian M, et al. Genital HPV infection in Indian HIV-seropositive men who have sex with men. Sex Transm Dis. 2017;44(3):173–80. https://doi.org/10.1097/OLQ.0000000000000564.

    Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Jiang S, Dong Y. Human papillomavirus and oral squamous cell carcinoma: a review of HPV-positive oral squamous cell carcinoma and possible strategies for future. Curr Probl Cancer. 2017;41(5):323–7. https://doi.org/10.1016/j.currproblcancer.2017.02.006.

    Article  PubMed  Google Scholar 

  48. 48.

    D’Souza G, Fakhry C, Sugar EA, Seaberg EC, Weber K, Minkoff HL, et al. Six-month natural history of oralversus cervical human papillomavirus infection. Int J Cancer. 2007;121(1):143–50. https://doi.org/10.1002/ijc.22667.

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Palefsky JM, Holly EA, Ralston ML, Jay N. Prevalence and risk factors for human papillomavirus infection of the Anal Canal in human immunodeficiency virus (HIV)-positive and HIV-negative homosexual men. J Infect Dis. 1998;177(2):361–7. https://doi.org/10.1086/514194.

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Muñoz N, Bosch FX, de Sanjosé S, Herrero R, Castellsagué X, Shah KV, et al. Epidemiologic Classification of Human Papillomavirus Types Associated with Cervical Cancer. N Engl J Med. 2003;348(6):518–27.

    Article  Google Scholar 

  51. 51.

    Hernandez AL, Efird JT, Holly EA, Berry JM, Jay N, Palefsky JM. Risk factors for anal human papillomavirus infection type 16 among HIV-positive men who have sex with men in San Francisco. JAIDS J Acquir Immune Defic Syndr. 2013;63(4):532–9. https://doi.org/10.1097/QAI.0b013e3182968f87.

    Article  PubMed  Google Scholar 

  52. 52.

    Raghavendran A, Hernandez AL, Lensing S, Gnanamony M, Karthik R, Sivasubramanian M, et al. Genital human papillomavirus infection in Indian HIV-seropositive men who have sex with men. Sex Transm Dis. 2017;44(3):173–80. https://doi.org/10.1097/OLQ.0000000000000564.

    Article  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Parisi SG, Cruciani M, Scaggiante R, Boldrin C, Andreis S, Bello FD, et al. Anal and oral human papillomavirus (HPV) infection in HIV-infected subjects in northern Italy: a longitudinal cohort study among men who have sex with men. BMC Infect Dis. 2011;11(1):150.

    Article  Google Scholar 

  54. 54.

    Prendes BL, Wang SJ, Groppo ER, Eisele DW, Palefsky JM. Oral human papillomavirus infection in men who have sex with men with anal squamous intraepithelial lesions. Head Neck. 2016;38(S1):E399–405. https://doi.org/10.1002/hed.24006.

    Article  PubMed  Google Scholar 

  55. 55.

    Pathare SM, Gerstung M, Beerenwinkel N, Schaffer AA, Kannan S, Pai P, et al. Clinicopathological and prognostic implications of genetic alterations in oral cancers. Oncol Lett. 2011;2(3):445–51. https://doi.org/10.3892/ol.2011.271.

    Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Patel KR, Vajaria BN, Begum R, Desai A, Patel JB, Shah FD, et al. Prevalence of high-risk human papillomavirus type 16 and 18 in oral and cervical cancers in population from Gujarat, West India. J Oral Pathol Med. 2014;43(4):293–7. https://doi.org/10.1111/jop.12147.

    Article  PubMed  Google Scholar 

  57. 57.

    Nagpal JK, Patnaik S, Das BR. Prevalence of high-risk human papilloma virus types and its association with P53 codon 72 polymorphism in tobacco addicted oral squamous cell carcinoma (oscc) patients of eastern India. Int J Cancer. 2002;97(5):649–53. https://doi.org/10.1002/ijc.10112.

    CAS  Article  PubMed  Google Scholar 

  58. 58.

    Chaudhary AK, Pandya S, Mehrotra R, Bharti AC, Singh M, Singh M. Comparative study between the Hybrid Capture II test and PCR based assay for the detection of human papillomavirus DNA in oral submucous fibrosis and oral squamous cell carcinoma. Virol J. 2010;7(1):253.

    Article  Google Scholar 

  59. 59.

    Janbaz KH, Qadir MI, Basser HT, Bokhari TH, Ahmad B. Review risk for oral cancer from smokeless tobacco. Współczesna Onkol. 2014;3(3):160–4. https://doi.org/10.5114/wo.2014.40524.

    Article  Google Scholar 

  60. 60.

    Zhou J, Michaud DS, Langevin SM, McClean MD, Eliot M, Kelsey KT. Smokeless tobacco and risk of head and neck cancer: evidence from a case-control study in New England. Int J Cancer. 2013;132(8):1911–7. https://doi.org/10.1002/ijc.27839.

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Yardimci G. Precancerous lesions of oral mucosa. World J Clin Cases. 2014;2(12):866.

    Article  Google Scholar 

  62. 62.

    Gupta S, Gupta O, Singh R, Tripathi A. Prevalence of oral cancer and pre-cancerous lesions and the association with numerous risk factors in North India: A hospital based study. Natl J Maxillofac Surg. 2014;5(2):142.

    Article  Google Scholar 

  63. 63.

    Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, et al. Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1. Science (80- ). 2011;333(6046):1154–7.

    CAS  Article  Google Scholar 

  64. 64.

    Benson E, Li R, Eisele D, Fakhry C. The clinical impact of HPV tumor status upon head and neck squamous cell carcinomas. Oral Oncol. 2014;50(6):565–74. https://doi.org/10.1016/j.oraloncology.2013.09.008.

    Article  PubMed  Google Scholar 

  65. 65.

    Braakhuis BJM, Snijders PJF, Keune W-JH, Meijer CJLM, Ruijter-Schippers HJ, Leemans CR, et al. Genetic patterns in head and neck cancers that contain or lack transcriptionally active human papillomavirus. JNCI J Natl Cancer Inst. 2004;96(13):998–1006. https://doi.org/10.1093/jnci/djh183.

    CAS  Article  PubMed  Google Scholar 

  66. 66.

    Gillison ML. Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Semin Oncol. 2004;31(6):744–54. https://doi.org/10.1053/j.seminoncol.2004.09.011.

    Article  PubMed  Google Scholar 

  67. 67.

    Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, et al. The Mutational Landscape of Head and Neck Squamous Cell Carcinoma. Science (80- ). 2011;333(6046):1157–60.

    CAS  Article  Google Scholar 

  68. 68.

    Adelstein DJ, Ridge JA, Gillison ML, Chaturvedi AK, D’Souza G, Gravitt PE, et al. Head and neck squamous cell cancer and the human papillomavirus: Summary of a National Cancer Institute State of the Science Meeting, November 9–10, 2008, Washington, D.C. Head Neck. 2009;31(11):1393–422.

    Article  Google Scholar 

  69. 69.

    Rettig EM, D’Souza G. Epidemiology of head and neck Cancer. Surg Oncol Clin N Am. 2015;24(3):379–96. https://doi.org/10.1016/j.soc.2015.03.001.

    Article  Google Scholar 

  70. 70.

    Palefsky JM, Holly EA, Efirdc JT, Da Costa M, Jay N, Berry JM, et al. Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men. AIDS. 2005;19(13):1407–14. https://doi.org/10.1097/01.aids.0000181012.62385.4a.

    Article  PubMed  Google Scholar 

  71. 71.

    Palefsky JM, Holly EA, Ralston ML, Da Costa M, Greenblatt RM. Prevalence and risk factors for anal human papillomavirus infection in human immunodeficiency virus (HIV)–positive and high-risk HIV-negative women. J Infect Dis. 2001;183(3):383–91. https://doi.org/10.1086/318071.

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Cameron JE, Hagensee ME. Human papillomavirus infection and disease in the HIV+ individual. Cancer Treat Res. 2007;133:185–213. https://doi.org/10.1007/978-0-387-46816-7_7.

    CAS  Article  PubMed  Google Scholar 

  73. 73.

    Palefsky J. Biology of HPV in HIV infection. Adv Dent Res. 2006;19(1):99–105. https://doi.org/10.1177/154407370601900120.

    CAS  Article  PubMed  Google Scholar 

  74. 74.

    Beachler DC, Kreimer AR, Schiffman M, Herrero R, Wacholder S, Rodriguez AC, et al. Multisite HPV16/18 Vaccine Efficacy Against Cervical, Anal, and Oral HPV Infection. J Natl Cancer Inst. 2016;108(1):djv302.

    Article  Google Scholar 

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Acknowledgements

The authors thank: Heather Helsing and Christopher Scott Weatherly for review and editing of the manuscript; the HPV Infection in Indian Men (HIIM) study staff; and the study participants for their time and dedication.

Funding

This work was supported by National Cancer Institute’s AIDS Malignancy Consortium grant number AMC - U01 CA121947. This study was also funded by the Indian Council of Medical Research Grant No: HIV/INDO-US/32/2007- ECD-II. The funding bodies had no role in the design of the study, in the collection, analysis, and interpretation of data, or in writing the manuscript.

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All authors contributed to the interpretation of data and the overall intellectual content of the paper, and drafting and editing of the manuscript. ALH, JP, and DM, also contributed to the study design. RK and MS also contributed to data collection. ALH, SL, JYL and JP also contributed to data analysis. AR, MG, RK, MDC, JP and PA also contributed to collecting, analyzing and interpreting laboratory data. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Alexandra L. Hernandez.

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All procedures were performed after obtaining written informed consent from participants. The study was approved by the Committee on Human Research of UCSF, and the Institutional Review Boards of both CMC and HT.

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The authors declare that they have no competing interests.

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Supplementary Information

Additional file 1: Supplementary File 1.

Supplement 1 - Questionnaire, English language version of the Questionnaire used in the study.

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Hernandez, A.L., Karthik, R., Sivasubramanian, M. et al. Prevalence of oral human papillomavirus infection among Indian HIV-positive men who have sex with men: a cross-sectional study. BMC Infect Dis 21, 675 (2021). https://doi.org/10.1186/s12879-021-06301-6

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Keywords

  • Human papillomavirus
  • HPV
  • HIV/AIDS
  • Oral cancer
  • MSM