Date of Award

Fall 2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Public Health

First Advisor

Niccolai, Linda

Abstract

Background. Virtually all cervical cancers and cases of recurrent respiratory papillomatosis (RRP) are caused by human papillomavirus (HPV) as well as a large proportion of anal, penile, oropharyngeal, vulvar, and vaginal cancers and anogenital warts (AGW). Vaccination with the nonvalent HPV vaccine (9vHPV) is proven to prevent a significant proportion of HPV-associated diseases. Adoption of large-scale HPV vaccination programs by US public institutions requires careful consideration of the cost to benefit ratio of each program through economic evaluations. US Uniformed Armed Forces (USUAF) HPV vaccination policy would benefit from economic evaluations that consider the unique population and institutional characteristics of the USUAF. The purpose of this dissertation is to inform HPV vaccination policy in a unique US population by calculating HPV-associated disease burden in the USUAF (Chapter 1), determining the health benefits from several HPV vaccination strategies (Chapter 2), and evaluating the cost to benefit ratios of HPV vaccination in the USUAF (Chapter 3). Methods. Veteran Health Administration medical encounter databases were analyzed for HPV-associated disease outcomes including anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancers, anogenital warts (AGW), and recurrent respiratory papillomatosis (RRP) diagnosed between October 1999 and February 2021. Age-/sex-standardized incidence rates (IRs), and incidence rate ratios (IRRs) were analyzed by sex. HPV-associated disease counts prevented by HPV vaccination were estimated. Next, a compartmental HPV transmission and disease development model was utilized to evaluate vaccination, immunity, and disease in six cohorts of USUAF entrants (age 18) for 75 years under five HPV vaccination strategies: one reference and four intervention strategies. Model cycles were defined as one year, during which cohort members were immunized via vaccination, developed an HPV-associated disease, or died. Main outcomes evaluated were vaccination costs, treatment costs, cases averted and quality adjusted life years (QALYs) gained, calculated as the difference in cases or QALYs lost between a reference immunization strategy and four intervention strategies. Parameter uncertainty was evaluated using a probabilistic sensitivity analysis. Results. Male Veterans demonstrated significantly higher incidence compared to the US general population for cancers of the anus (IRR = 1.23 [95% CI = 1.16, 1.32]), oropharynx (IRR = 1.64 [95% CI = 1.54, 1.74]), and penis (IRR = 1.50 [95% CI = 1.24, 1.82]) and RRP (IRR = 1.22 [95% CI = 1.01, 1.46]) and females for anal (IRR = 3.63 [95% CI = 2.16, 6.39]) cancer. Veterans experienced significantly lower incidence of AGW (Male IRR = 0.35 [95% CI = 0.33, 0.36], Female IRR = 0.10 [95% CI = 0.08, 0.12]) and vulvar cancer (IRR = 0.53 [95% CI = 0.32, 0.84]). Requiring vaccination of males and females at entry into USUAF is estimated to avert over 75 years 27,193 HPV-associated diseases and gain 6,035 QALYs compared to 9,148 averted cases and 2,082 QALYS gained when USUAF entrants electively chose vaccination. In the first 20 years of the program, total annual cases averted by required female vaccination outnumbered those under male required vaccination. Elective male and female vaccine uptake (current USUAF HPV vaccination policy) was the least costly strategy over 75 years. Requiring female or male and female vaccination had incremental cost-effectiveness ratios ($15,074 and $67,631, respectively) that are generally considered acceptable for implementation consideration. Male required vaccination alone was not cost-effective. Probabilistic sensitivity analysis identified vaccination targeted to females only (Females Required) as most likely to be cost-effective for WTP thresholds up to $75,000. At higher WTP values, universal vaccination of all entrants (Males & Females Required) had the highest probability of being cost-effective. Conclusions. HPV-associated disease burden among Veterans differed significantly from the general population for several cancers and AGW. When accounting for unique population and institutional characteristics, our model predicted health benefit outcomes associated with universal HPV vaccination policies for the USUAF population. Similar to results from other HPV transmission models, HPV-associated health benefits increased proportionately to vaccination participation. This dissertation’s results indicate that amending USUAF immunization policy to require female or male and female HPV vaccination at entry represent viable cost-effective options for the USUAF. Despite a heavily skewed sex distribution, the cost-effective viability of a sex-neutral HPV vaccination policy in the USUAF strengthens the growing body of evidence suggesting HPV vaccination is most effective when applied universally across sexes.

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