Health Economic Analysis of a Bivalent HPV Vaccine and the Value of Cross-Protection In a US Female Population

Background: Human papillomavirus (HPV) types 16/18 cause ~75% of cervical cancers (CC); ten other high‑risk types (10‑OHR) account for the majority of remaining cases.  An HPV vaccine offering bivalent efficacy against types 16/18 and cross‑protection against 10‑OHR is available in the US.

Objectives: To evaluate the benefits of HPV vaccination and estimate the value of cross‑protection in US females.

Methods: A lifetime Markov model that simulates the natural history of HPV infection and cervical disease was developed.  Populations of interest were naïve 18-year-old females i.e. those who are HPV DNA negative and seronegative (P1) and 18‑year‑olds regardless of HPV DNA or serostatus (P2).  Bivalent (HPV16/18) and cross‑protection (10‑OHR) cervical intraepithelial neoplasia (CIN) 2+ efficacies were assumed as 98.4% and 68.4% for P1 and 92.4% and 47.3% for P2, respectively.  Model outcomes included abnormal Papanicolaou (Pap) tests, CINs, CC cases and deaths, and incremental cost‑effectiveness ratios (ICERs) per quality‑adjusted life‑year (QALY) discounted at 3%/year.

Results: Vaccinating 100,000 18‑year‑old US females with a bivalent-only vaccine prevented 26,139 abnormal Paps, 9,376 CINs, 498 CC cases, and 116 CC‑related deaths, respectively for P1, versus no vaccination; cross‑protection prevented an additional 19,841, 5,593, 74, and 16 corresponding events.  For P2, the bivalent vaccine prevented 23,958 abnormal Paps, 8,615 CINs, 452 CC cases, and 104 CC‑related deaths, respectively; cross‑protection prevented an additional 13,213, 3,743, 47, and 10 events.  Vaccination was cost‑effective below a threshold of $25,000 per QALY gained in both target populations. The bivalent vaccine produced ICERs of $14,400 (P1) and $20,500 (P2) per QALY gained versus no vaccination; adding cross‑protection resulted in vaccination being dominant (less expensive, more effective) in P1 and an ICER of $3,800 per QALY gained in P2.

Conclusions: Model results suggest that a HPV vaccination offers substantial clinical and economic benefits in 18-year-old US females.  Cross-protection further strengthens these benefits.