Evaluation of upper age limits for HPV vaccination of US men for prevention of oropharyngeal cancers: A microsimulation-based modeling study

Published

January 19, 2023

Author(s)

Rebecca Landy, Gregory Haber, Barry Graubard, Nicole Campos, Stephen Sy, Jane Kim, Emily Burger, Li Cheung, Hormuzd Katki, Maura Gillison, Anil Chaturvedi

Abstract

Importance: HPV-positive oropharyngeal cancer is the most common HPV-associated cancer in the United States. Although permissible, the benefit of vaccination of US men aged 27-45 is uncertain because the natural history of HPV-induced oropharyngeal carcinogenesis remains poorly characterized. Objective: Estimate ages at acquisition of oral HPV16 infections that cause oropharyngeal cancers (i.e., causal infections); determine the benefit of vaccination of men aged 27-45 for prevention of HPV-positive oropharyngeal cancer. Design: Microsimulation-based, individual-level, state-transition modeling of oral HPV16 and HPV16-positive oropharyngeal cancer, calibrated to US population-level data. Setting: US population of men. Participants: Men aged 15-74 in 2021. Exposure: HPV vaccination. Main outcomes and measures: Simulated natural history of oral HPV16-induced oropharyngeal carcinogenesis in the absence of vaccination (incidence, persistence/clearance of infection, cancer-latency, and ages at acquisition of causal infections). Modeled impact of male vaccination at different upper age-limits for prevention of HPV16-positive oropharyngeal cancer, accounting for direct- and indirect/herd-effects of male and female vaccination. Results: According to model projections, in the absence of vaccination, the median estimated lifetime (15-74 years) probability of oral HPV16 infection is 10.5% (range=9.7%-11.7%) in US men; incidence peaks around age 25 (median=4.3/1,000; range=3.6-6.4) and declines thereafter; and 1-in-6 incident infections persists for 20+ years. Median latency from infection acquisition to detected cancer is 36 years (interquartile-range=30-42). Most causal oral HPV16 infections (71%) are acquired by age 26, and 28% are acquired between ages 27-45. In the absence of vaccination, among men aged 15-45 in 2021 (1976-2006 birth cohorts), 218,598 HPV16-positive oropharyngeal cancers are estimated to occur through age 75. Of these, 123,985 (57%) are vaccine-preventable, and status-quo vaccination of men through age 26 is estimated to prevent 95% of these preventable cancers. Even assuming 100% vaccination in 2021, extending the upper age-limit to 30, 35, 40, and 45 for men aged 27-45 (1976-1994 cohorts) is estimated to yield small incremental benefit (3.0%, 4.1%, 4.7%, and 5.1% additional cancers prevented, respectively). Conclusions and Relevance: Model projections suggest that most causal oral HPV16 infections in men are acquired by age 26. We estimate diminishing benefit from vaccination of current birth cohorts of US men aged 27-45 for prevention of HPV16-positive oropharyngeal cancers.

Citation

Journal of the National Cancer Institute

Volume

115

Issue

4

Pub Type

Journals

Download Paper

https://doi.org/10.1093/jnci/djad009

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Keywords

Microsimulation, HPV, Vaccination, Cancer

Citation

Landy, R. , Haber, G. , Graubard, B. , Campos, N. , Sy, S. , Kim, J. , Burger, E. , Cheung, L. , Katki, H. , Gillison, M. and Chaturvedi, A. (2023), Evaluation of upper age limits for HPV vaccination of US men for prevention of oropharyngeal cancers: A microsimulation-based modeling study, Journal of the National Cancer Institute, [online], https://doi.org/10.1093/jnci/djad009, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=934500 (Accessed October 13, 2025)