The current Singapore school-based national immunization program (NIP) includes bivalent HPV vaccine (2vHPV) for females 13 years of age. The 9-valent HPV vaccine (9vHPV) provides additional benefits through direct protection against seven additional HPV types. This study assesses the health impact and cost-effectiveness of 9vHPV for females and males (gender neutral vaccination; GNV) vs. 2vHPV for females only vaccination (FOV) immunization strategies accounting for potential cross-protection for 2vHPV.

A validated dynamic transmission model was adapted to compare two NIP strategies for 13-14 years old: 9vHPV GNV and 2vHPV FOV. Analyses estimated health and economic impact with and without cross-protection for 2vHPV, defined as protection against non-vaccine HPV 31/33/45 types. HPV-associated health outcomes included cervical intraepithelial neoplasia (CIN), cervical, vaginal, vulvar, anal, and penile cancers as well as genital warts. All analyses took payer and lifetime perspectives with a vaccination coverage rate of 91.5%. Costs (SGD 2018) and outcomes were discounted at 3%.

Compared to 2vHPV FOV, 9vHPV GNV strategy prevented more cases of HPV-related diseases and cancers (2,032 cervical cancer (CC), 12,467 CIN2/3, 2 vaginal, 6 vulvar, 148 anal and 47 penile cancer, and 312,088 genital warts) and deaths (1,014 CC, 1 vaginal, 2 vulvar, 40 anal, and 14 penile). The incremental cost-effectiveness ratio (ICER) was SGD 20,547. After accounting for cross-protection, 9vHPV GNV strategy showed an incremental reduction of 1,936 CC, 11,959 CIN2/3, and 147 anal cancer cases, and 968 CC deaths with ICER of SGD 21,441, 4.35% increase due to cross-protection. Sensitivity analyses of different scenarios showed similar findings.

9vHPV GNV strategy, compared to 2vHPV FOV strategy, results in greater public health impact in Singapore, even after accounting for cross-protection benefit from 2vHPV. With an implicit willingness-to-pay threshold as ICER of less than SGD 45,000/QALY, a 9vHPV GNV strategy is considered cost-effective in Singapore.