Effect of Human Papillomavirus 16/18 L1 virus like particle vaccine among women with pre-existing infection

A Cochrane review «Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors»1 «Arbyn M, Xu L, Simoens C et al. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev 2018;(5):CD009069. »3 included 26 trials with a total of 73 428 participants. Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical intraepithelial neoplasia grade 2 and above (CIN2+), CIN grade 3 and above (CIN3+), and cervical cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide. Regardless of HPV DNA status in younger women (aged 15 to 26), HPV vaccines reduced the risk of CIN2+, CIN3+, and adenocarcinoma-in-situ (AIS) associated with HPV16/18. (table «HPV vaccine effects on cervical lesions in adolescent girls and women unselected for HPV DNA status at baseline»1). The reduction in any CIN3+ differed by vaccine type (bivalent vaccine: RR 0.55, 95% CI 0.43 to 0.71 and quadrivalent vaccine: RR 0.81, 95% CI 0.69 to 0.96). In women vaccinated at 24 to 45 years of age, the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women, which may be due to previous exposure to HPV. Studies were not of sufficient power or duration to evaluate cervical cancer outcomes.

A Cochrane review «Human papillomavirus (HPV) vaccination in women with conisation»2 «Kapp P, Schmucker C, Siemens W, et al. Human papillomavirus (HPV) vaccination in women with conisation. Cochrane Database Syst Rev 2025;9(9):CD016121. »2 included 13 studies (2 RCTs, 11 non-randomized studies), with 21 453 women with conisation (women with cervical intraepithelial neoplasia 2 and 3 [CIN 2–3] typically undergo cervical conisation after persistent infections with high-risk HPV types). HPV vaccination compared to no vaccination reduced the risk of CIN 2+ (RCTs: RR 0.40, 95% CI 0.26 to 0.63; 2 RCTs, n=420; non-randomized trials: hazard ratio HR 0.49, 95% CI 0.27 to 0.89; 5 trials, n=19 059; odds ratio 0.23, 95% CI 0.05 to 0.97; 3 trials, n=928; RR 0.24, 95% CI 0.13 to 0.46; 3 trials, n=1027), but with low-certainty of evidence.

In a randomised trial «Hildesheim A, Herrero R, Wacholder S, Rodriguez AC, Solomon D, Bratti MC, Schiller JT, Gonzalez P, Dubin G, Porras C, Jimenez SE, Lowy DR, Costa Rican HPV Vaccine Trial Group. Effect of human papillom»1 in Costa Rica 2189 women (aged 18 to 25 years) with pre-existing infection were randomly assigned to receive 3 doses of a bivalent HPV-16/18 L1 protein viruslike particle AS04 candidate vaccine (n=1 088) or a control hepatitis A vaccine (n=1 101) over 6 months. Clearance rates for HPV-16/18 infections at 6 months were 33.4% (82/248) in the HPV vaccine group and 31.6% (95/298) in the control group (vaccine efficacy for viral clearance VEVC, 2.5%; 95% CI –9.8% to 13.5%) and at 12 months 48.8% (86/177) and 49.8% (110/220) respectively (VEVC –2.0%; 95% CI –24.3% to 16.3%). There was no evidence of a therapeutic effect for other oncogenic or nononcogenic HPV categories.

Comment: The quality of evidence is downgraded by study quality (more than 20% loss to follow up).

The following decision support rules contain links to this evidence summary:

• Avoiding Human Papillomavirus vaccination in patients with pre-existing infection «http://www.ebmeds.org/ebmeds/ebmeds_home.asp?mode=scripts&submode=view&id=scr00609&country=UK»1