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

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 prevention of CC. The most important of these surrogate markers is CIN2/3 (CIS), because (a) it is clearly a CC precursor, (b) its prompts rapid treatment, and (c) eradication of CIN2/3 leads to alleviation of CC burden. The combined analysis of the clinical GARDASIL trials show that the burden of HPV-related disease is significant. Accordingly, 27% of enrolled subjects were either seropositive or PCR-positive to HPV6, 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 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 has been well-tolerated. It can be anticipated that this vaccine will lower a woman’s life-time risk for developing CC and substantially reduces the morbidity, mortality and clinical costs of HPV-related disease. # 2006 Elsevier Ireland Ltd. All rights reserved.