Oncogenic Oral Human Papillomavirus Clearance Patterns Over 10 years.

BACKGROUND:Effective screening for Oropharyngeal cancer (OPC) is lacking. Four oncogenic HPV clearance definitions were explored to understand long-term natural history for persistent oncogenic oral HPV (oncHPV), the precursor of OPC. METHODS:Prospective multicenter cohort of participants living with/at-risk for HIV, with oral rinse and gargle samples collected every 6-12 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 2 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 1833 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 oHPV16 developed incident OPC (IR=1.62 per 100 person-years,95%CI=0.41,6.4). Many with oHPV16 persisted ≥5 years (and/or developed HPV-OPC) 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 OPC and contextualized risk levels for those with oral HPV16 infection.