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Multicenter Study
. 2024 Apr 3;33(4):516-524.
doi: 10.1158/1055-9965.EPI-23-1272.

Oncogenic Oral Human Papillomavirus Clearance Patterns over 10 Years

Gypsyamber D'Souza  1   2 , Sakshi R Tewari  1 , Tanya Troy  1   2 , Jennifer Webster-Cyriaque  3 , Dorothy J Wiley  4 , Cecile Delille Lahiri  5 , Frank Joseph Palella  6 , Maura L Gillison  7 , Howard D Strickler  8 , Linda Struijk  9 , Tim Waterboer  10 , Ken Ho  11 , Jennafer Kwait  12 , Jason Lazar  13 , Kathleen M Weber  14 , Carole Fakhry  1   2
Affiliations
Multicenter Study

Oncogenic Oral Human Papillomavirus Clearance Patterns over 10 Years

Gypsyamber D'Souza et al. Cancer Epidemiol Biomarkers Prev. .

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.

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Conflict of interest statement

TW serves on advisory boards for MSD (Merck) Sharp & Dohme. CDL serves on an advisory board for Theratechnologies, LLC and receives grant funding from Merck. DW serves as External Advisory Board Member in UCLA Clinical Translational Science Institute, and as Member of California HPV Vaccination Roundtable and National HPV Roundtable. All other authors have no conflicts.

Figures

Figure 1:
Figure 1:
Natural history of oral HPV16 (shaded circle indicates positive and unshaded circle indicates negative) in semi-annual testing and HPV16 E6 serology results (red triangle indicates positive and unshaded triangle indicates negative) among participants later diagnosed with HPV related oropharyngeal cancer (blue diamond).
Figure 2.
Figure 2.
Clearance of prevalent (panel A) and incident (panel B) oncogenic oral HPV infections over 10 years.
Figure 3:
Figure 3:
Examples of the pattern of oncogenic oral HPV DNA among subjects who did not clear their infections (by clear3). Included here are participants with oral HPV16 detected, who had at least 5 years of follow-up, stratified by whether clear1 and clear2 also considered these infections not to have cleared, or whether these alternative definitions considered the infections to have cleared. The top panel includes infections considered persistent (i.e. not to have cleared) by all three definitions (clear1, clear2 and clear3); the middle panel includes infections considered persistent by clear2 and clear3 but cleared by clear 1; the bottom panel includes infections considered persistent by clear3 but cleared by clear2 or clear 1. Legend: 1= HPV16 positive (Dark grey), 0=HPV16 negative (Light grey), * = missed visit, no test result (white).
See this image and copyright information in PMC

References

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