Risk factors for oral HPV persistence and HPV-associated cancer
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Background: Persistent human papillomavirus (HPV) infection is a well-known cause of cervical and anogenital cancers. In the past decade, oral HPV infection was established as a cause of oropharyngeal squamous cell carcinoma (OPSCC), but risk factors for oral HPV persistence are poorly understood. Increasing HPV-associated OPSCC has been reported in several Western countries, predominantly in younger white men. Trends in Asian populations have not been well-described, but may differ since the epidemiology of HPV-associated cancers varies by age, sex, geography and race/ethnicity. Objectives: We aimed to investigate potential factors associated with oral HPV persistence, including 1) serum cytokines, 2a) recreational drug use and 2b) medication use. We also explored: 3) the epidemiology of OPSCC and other potentially HPV-associated cancers in Singapore, a Southeast Asian country. Methods: For aims 1 and 2, participants were enrolled in the “Persistence of Oral Papillomavirus Study” (POPS), a U.S.-based cohort study. Oral rinse samples were collected semi-annually for HPV DNA testing. Blood samples were collected for cytokine testing. Drug and medication use were assessed via questionnaire. For aim 3, the epidemiology of potentially HPV-associated cancers in Singapore was described, using cancer registry data. Data were analyzed using Wei-Lin-Weissfeld regression (aims 1&2) and Joinpoint regression (aim 3). Results: From 2010 to 2014, 1,666 participants were enrolled in POPS. Oral HPV prevalence was 36% and median time to clearance was 6.3 months. Higher TNF-α concentration was associated with decreased oral HPV clearance in men (highest vs. lowest quartile, adjusted hazard ratio [aHR]=0.52, 95%CI=0.34-0.79) and women (aHR=0.76, 95%CI=0.55-1.04), p-interaction=0.049. Cocaine use (aHR=0.60, 95%CI=0.41-0.88) and antipsychotic medication use (aHR=0.75, 95%CI=0.57-0.99) were also each associated with reduced clearance. In Singapore, OPSCC incidence increased in both genders (men 1993-2012, annual percentage change [APC]=1.9%, p<0.001; women 1968-2012, APC=2.0%, p=0.01), in contrast to non-oropharyngeal head and neck cancers. The incidence of HPV-associated cancers varied by ethnicity. Conclusions: Some immunomodulatory agents, including high serum TNF-α, cocaine, and antipsychotic medication may reduce oral HPV clearance. Similar to trends in other countries, OPSCC incidence increased in Singapore in recent years, suggesting the epidemiologic shift in head and neck cancers is not just occurring in the West.