WITHDRAWN: Efficacy of a quadrivalent HPV (types 6, 11, 16, 18) L1 VLP vaccine against cervical intraepithelial neoplasia grades 1–3 and adenocarcinoma in situ: A combined analysis

Abstract

There are solid research data to support the construction of a quadrivalent (HPV6, 11, 16 and 18) L1 VLP vaccine. Accordingly, the two HR-HPV types (16 and 18) cover around 70% of all CCs, 50‐70% of high-grade CIN lesions, 70% of other HPV-related genital cancers, and some 25% of low-grade CIN lesions. Similarly, in males, 70% of all anal cancers are caused by HPV16 and HPV18, as are 70% of all AIN2/3 lesions. There are several potential surrogate endpoint markers that can be used in evaluating the efficacy of prophylatic HPV vaccines in preventionofCC.The mostimportantofthesesurrogatemarkersisCIN2/3(CIS),because (a)itisclearlyaCCprecursor,(b)itspromptsrapid treatment, and (c) eradication of CIN2/3 leads to alleviation of CC burden. The combined analysis of the clinical GARDASIL 1 trials show thattheburdenofHPV-related diseaseissignificant. Accordingly,27% ofenrolledsubjectswere eitherseropositiveor PCR-positive toHPV6, 11, 16 or 18. Altogether, 8.7% of placebo recipients developed CIN during the follow-up period, of which a significant proportion was due to HPV6, 11, 16 or 18. Importantly, GARDASIL 1 is 100% effective in preventing CIN3 and AIS as well as CIN2 in the per-protocol population. In the modified-intention-to-treat population, vaccine efficacy against CIN3 and AIS was also 100% (95% CI 91‐100). In all these studies, GARDASIL 1 has been well-tolerated. It can be anticipated that this vaccine will lower a woman’s life-time risk for developing CC and