Efficacy of HPV vaccination among seropositive, DNA negative cohorts.

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10552 Background: Prophylactic HPV vaccination of naïve cohorts is known to be highly effective in the prevention of incident HPV infection and HPV-associated cervical premalignancy. Conversely, vaccination of women with active (DNA+) HPV infections has been demonstrated to be ineffective. Vaccine efficacy among previously exposed, but currently uninfected women, i.e. those who have serological evidence of a prior HPV infection without corresponding detectable HPV DNA, remains incompletely defined. This meta-analysis assessed the serotype-specific efficacy of prophylactic HPV vaccination against HPV16/18 persistent infection (PI) and cervical intraepithelial neoplasia (CIN) among seropositive, DNA negative (SPDN) women enrolled to RCTs of HPV L1-based vaccines. Methods: The study protocol was prospectively registered on PROSPERO (CRD42020206888). Searches were conducted on 08/16/20 on MEDLINE, EMBASE, SCOPUS and CENTRAL. RCTs of L1-based prophylactic bivalent or quadrivalent HPV vaccines, reporting serotype-specific clinical efficacy endpoints in the HPV16/18 seropositive, DNA-negative populations were included. Two authors independently screened studies, extracted data and assessed for bias. Data for SPDN women were extracted from subgroup analyses within primary and secondary publications, publication supplements, and manufacturers' clinical study reports. Relative risks (RR) of 6-month persistent infection (6mPI), 12-month persistent infection (12mPI), CIN1+ and CIN2+ were pooled using a random-effects model. Results: A total of 1727 citations were reviewed. 8 studies, with a total of 9569 SPDN participants, met all eligibility criteria. The relative risk of 6mPI (RR: 0.22, 95% CI 0.08-0.61, p = 0.018), 12mPI (RR: 0.20, 95% CI 0.05-0.80, p = 0.035), CIN1+ (RR:0.13, 95% CI 0.05-0.30, p = 0.003) and CIN2+ (RR: 0.15, 95% CI 0.04-0.59, p = 0.022) was significantly reduced in the vaccinated compared to the unvaccinated group. The number needed to vaccinate (NNV) to prevent one case of CIN1+ and CIN2+ was 152 and 208 respectively. Conclusions: Our findings suggest high serotype-specific efficacy for HPV vaccination among cohorts of women with evidence of prior HPV 16/18 infections. Women without DNA evidence of active infection may be seronegative, implying naïve status and > 99% efficacy; or seropositive, implying SPDN status and 87% efficacy against CIN1+ for HPV 16/18. Women without DNA evidence of HPV 16/18 infection should be offered prophylactic HPV vaccination regardless of prior exposure history.