Targeted Literature Review for Estimating Median Age of Causal Human Papilloma Virus Infection to Oropharyngeal Cancer

OBJECTIVES: Due to the long latency of Human Papillomavirus (HPV) associated Oropharyngeal Cancer(OPC) and lack of screening program, the natural history of OPC progression is not well-characterized. We aimed to summarize models estimating the natural history from infection to OPC and identify the key factors determining the shape of causal infection.

METHODS: Targeted literature review in PubMed and Embase identified studies reporting on natural history model and on either OPC/HPV positive (HPV+) OPC incidence, percentage of patients acquiring HPV+ OPC, or median age of causal infection.

RESULTS: Five eligible studies were identified: two utilized microsimulation models to understand the natural history of oral HPV infection and its progression to OPC, while the remaining examined the impact of increasing HPV vaccination rates on OPC using population dynamic, Markov and Age-period-cohort forecasting models. Incidence and prevalence were informed by SEER and NHANES in most studies. Landy et al, reported a median age of 23 years for causal infection, with a median latency period of 39 years, and 29% of patients acquiring HPV+ OPC between ages 27 and 45. Damgacioglu et al. developed a microsimulation model focusing on genotype-specific HPV infection persistence and OPC progression. Choi et al. calibrated the progression rates from HPV infection to OPC using SEER data on HPV+ OPC incidence rates. Zhang et al. determined HPV-related OPC proportions from SEER tumor HPV testing data. Zhong et al. incorporated an epidemiologic model, validating predictions against SEER incidence rates. Overall, the shape of the age distribution for acquisition of causal infection was influenced by data inputs and assumptions underlying the OPC progression, oral HPV acquisition, oral HPV clearance, and heterogeneity in oral sexual behaviors and partnerships.

CONCLUSIONS: Few US-specific studies estimate the median age of causal infection. Results may not be generalizable to countries with varying key determinants of median age of causal HPV infection.