The association of medication use with clearance or persistence of oral HPV infection

Abstract

Purpose Persistent oral human papillomavirus (HPV) infection increases risk for oropharyngeal carcinoma, and people living with HIV have higher rates of oral HPV infection and related cancers. Some prescription medications have immunomodulatory effects, but the impact of medication use on oral HPV natural history is unknown. Methods Scope® oral rinse-and-gargle samples were collected semi-annually from 1,666 participants and tested for 37 types of oral HPV DNA using PCR; 594 HPV-infected participants with 1,358 type-specific oral HPV infections were identified. Data were collected on recent (past 6 months) use of medications. The relationship between medication use and oral HPV clearance was evaluated using Wei-Lin-Weissfeld regression, adjusting for biologic sex, prevalent vs. incident infection, age, HIV status and CD4+ T-cell count. Results Out of 11 medications examined, oral HPV clearance was significantly reduced in participants reporting recent use of antipsychotics (HR=0.75, 95% CI=0.57–0.99), anxiolytics/sedatives (HR=0.78, 95% CI=0.63–0.96) and antidepressants (HR=0.82, 95% CI=0.67–0.999). Among antipsychotics users, effect modification by HIV status was observed, with reduced clearance in HIV-infected (HR=0.67, 95%: CI 0.49–0.91), but not HIV-uninfected participants (p-interaction=0.009). After adjusted analysis, antipsychotic use remained significantly associated with reduced oral HPV clearance overall (aHR=0.75, 95% CI=0.57–0.99), and when restricted to only HIV-infected participants (aHR=0.66, 95% CI=0.48–0.90). After adjustment, anxiolytic/sedative use and antidepressant use were no longer significantly associated with reduced oral HPV clearance. Conclusions Some medications were associated with decreased oral HPV clearance, most notably antipsychotic medications. These medications are prescribed for conditions that may have immunomodulating effects, so characteristics of underlying illness may have partially contributed to reduced oral HPV clearance.

Increased risk of oropharyngeal cancers mediated by oral human papillomavirus infection: Results from a Canadian study

“…37 The factors increasing the risk of oral HPV infection, progression, and persistence ultimately leading to head and neck cancer remain unclear, and longitudinal studies will help answer these questions. 44 Our study has several strengths. 38 Also, the transmission of oral HPV infection is more efficient when performing oral sex on infected female (vs male) genitals.…”

“…These avenues are promising considering that smoking, 41 periodontal diseases, 42 HIV status, 43 and immunoregulatory medications have been associated with oral HPV infection and head and neck cancer. 44 Our study has several strengths. The life course epidemiologic design of the study permitted the measurement of oral sex behaviors throughout participants' lives, but also of smoking and drinking habits, major risk factors for head and neck cancers, which helped us to control confounding.…”

Might Oral Human Papillomavirus (HPV) Infection in Healthy Individuals Explain Differences in HPV-Attributable Fractions in Oropharyngeal Cancer? A Systematic Review and Meta-analysis

“…A recent systematic review of the incidence and clearance of oral HPV infection noted that estimates varied notably between regions [39]. Previous data showed that male sex, older age, current smoking [40], some medications with immunomodulatory effects [41], and HPV16 integration [42] may play a role in oral HPV persistence in healthy individuals.…”

Head and neck squamous cell carcinoma and its correlation with human papillomavirus in people living with HIV: a systematic review

“…HPV is a DNA virus that can cause lesions anywhere on the cutaneous surface, including the extremities, genitalia and oral mucosa, and establish a persistent oral infection caused by reduced infection clearance and an increased viral load, seen as the presumed precursor for HPV-related oropharyngeal squamous cell carcinoma [ 81 , 84 ]. However, it cannot establish an infection in healthy skin or mucosa [ 85 ].…”

“…HPV-related HNSCC have been found to have a Standardized Incidence Ratio (SIR) of 3.2 (95% CI = 2.5-3.4), significantly higher than the general population [ 79 ]. HIV-infected persons have, as a matter of fact, a 2-3-fold higher prevalence of oral HPV-infection, compared to the general population, with a highly-variable frequency of high-risk serotypes [ 67 , 84 ]. Likewise, the incidence of HPV-related HNSCC in PLWH is 2 to 6 times higher than the one in the general population [ 75 , 79 , 88 , 89 ].…”