Oncogenic Oral Human Papillomavirus Clearance Patterns over 10 Years
Gypsyamber DʼSouza, Sakshi R. Tewari, Tanya Troy, Jennifer Webster‐Cyriaque, Dorothy J. Wiley, Cecile D. Lahiri, Frank J. Palella, Maura L. Gillison, Howard D. Strickler, Linda Struijk, Tim Waterboer, Ken Ho, Jennafer Kwait, Jason Lazar, Kathleen M. Weber, Carole Fakhry
Abstract
BACKGROUND: Effective screening for oropharyngeal cancer is lacking. Four oncogenic HPV clearance definitions were explored to understand long-term natural history for persistent oncogenic oral HPV (oncHPV), the precursor of oropharyngeal cancer. METHODS: Prospective multicenter cohort of participants living with/at-risk for HIV, with oral rinse and gargle samples collected every 6 to 12 months for up to 10 years and tested for oncHPV. HPV clearance definitions included 1 (clear1), 2 (clear2), 3 (clear3) consecutive negatives, or being negative at last two visits (clearlast). RESULTS: Median time to clearance of oncHPV exceeded 2 years for conservative definitions (clear3: 2.38, clearlast: 2.43), but not lenient (clear1: 0.68, clear2: 1.15). By clear3, most incident infections cleared at 2, 5, 8 years (55.1%, 75.6%, 79.1%), contrary to prevalent infections (37.1%, 52.5%, 59.5%, respectively). In adjusted analysis, prevalent oncHPV, older age, male sex, and living with HIV were associated with reduced clearance. Of 1,833 subjects screened, 13.8% had prevalent oncHPV and 47.5% of those infections persisted ≥5 years, representing 6.5% of persons screened. Two men with prevalent oral HPV16 developed incident oropharyngeal cancer [IR = 1.62 per 100 person-years; 95% confidence interval (CI), 0.41-6.4]. Many with oral HPV16 persisted ≥5 years (and/or developed HPV-oropharyngeal cancer) among those with 2 (72.2%), ≥2 of first 3 (65.7%), or 3 (80.0%) consecutive positive oHPV16 tests, but not after 1 (39.4%). CONCLUSIONS: In our 10-year study, most incident infections cleared quickly. However, half of prevalent oncHPV persisted ≥5 years, suggesting increased risk with persistent oncHPV at >2 visits. IMPACT: We identified groups with persistent oncHPV at increased risk of oropharyngeal cancer and contextualized risk levels for those with oral HPV16 infection.