The difference in the effectiveness of human papillomavirus vaccine based on smoking status.

Aim: This study aimed to clarify (1) the effectiveness of human papillomavirus (HPV) vaccine against precancerous lesions of uterine cervical cancer and (2) the difference in these effectiveness based on smoking status.

Methods: This retrospective cross-sectional study considered women aged 20-24 who underwent cervical cancer screening in Saga City from April 2014 to March 2020. Cervical cytology and histological diagnosis were compared with or without HPV vaccination and smoking.

Results: The study included 7253 women (2467 vaccinated and 4786 unvaccinated). Among the vaccinated women, 462 were smokers, 2003 were nonsmokers: among the nonvaccinated women, the numbers were 1217 and 3554, respectively. 0.28% (7/2467) of participants with vaccination had HSIL+ compared to 0.77% (37/4786) without vaccination (odds ratio [OR] 0.36, 95% confidence interval [CI], 0.16-0.81). About 0.32% (8/2467) with vaccination had cervical intraepithelial neoplasia (CIN) 2+ compared to 0.69% (33/4786) without vaccination (OR 0.46, 95% CI, 0.21-1.00). Four women without vaccination had CIN3+. In nonsmokers, HPV vaccination significantly suppressed the incidence of HSIL+ from 0.42% (15/3554) to 0.1% (2/2003) (OR 0.21, 95% CI, 0.05-0.95), but the suppressive effect was not significant in smokers (OR 0.59, 95% CI, 0.22-1.56). In vaccinated women, the incidence of CIN2+ was 0.20% (4/2003) in nonsmokers and 0.87% (4/462) in smokers (OR 0.22, 95% CI, 0.05-0.89, p = 0.02).

Conclusions: HPV bivalent/quadrivalent vaccination is effective in protecting against CIN but insufficient in smokers. The nine-valent vaccine should be introduced into routine vaccination as soon as possible to prevent high-risk HPV infection other than 6/11/16/18.