A quadrivalent vaccine (HPV types 6, 11, 16, and 18) was evaluated in a multinational, double-blind, randomized controlled trial of 17,622 women aged 15 to 26 years (FUTURE I and II). Women received either the HPV vaccine or placebo at 0, 2, and 6 months; participants were assessed by clinical exam, Pap test, and HPV DNA testing for 4 or more years. Two analyses were reported. One group was considered to be HPV naive: negative to 14 HPV types. The second group was an ITT analysis, which approximates a sexually active population. The composite endpoint for cervical disease included the incidence of HPV-16/18-related, CIN 2, CIN 3, adenocarcinoma in situ, or invasive carcinoma. Outcomes were reported as follows:
Vaccine Efficacy of the Quadrivalent HPV Vaccine
CIN = cervical intraepithelial neoplasia; HPV = human papillomavirus; ITT = intention-to-treat.
|Population|| Point Estimate and 95% CI|
|HPV naive population for HPV-CIN 3 ||100% (90.5%-100%) for lesions associated with HPV 6, 11,16, or 18|
| ITT CIN 3||45.3% (29.8%-57.6%) for lesions associated with HPV 6, 11, 16, or 18|
This study also demonstrated decreased rates of abnormal Pap tests and subsequential diagnostic procedures. No cases of invasive cervical cancer were identified during the trial.
As largely expected based upon their mechanism of action, L1/2 HPV vaccines do not appear to impact pre-existing infections. The FUTURE II trial demonstrated a markedly lower vaccine efficacy rate in the total randomized study population, which included individuals positive for HPV at baseline, versus the "per-protocol" population (44% for lesions associated with HPV 16 or 18 and 17% for lesions associated with any HPV type vs. 98%, see table above). Additionally, an intermediate analysis of a randomized controlled trial primarily evaluating the efficacy of the HPV-16/18 vaccine in preventing infection found no effect on viral clearance rates in women aged 18 to 25 years who were positive at the time of study enrollment.
The type-specific vaccines, if successful in preventing invasive cancer, will offer protection for only a subset of cases, the proportion of which will vary worldwide. Using data from a multicenter case-control study conducted in 25 countries, it was estimated that a vaccine containing the seven most common HPV types could prevent 87% of cervical cancers worldwide. A vaccine with HPV-16 and HPV-18 types, the two most common strains, would prevent 71% of cervical cancers worldwide.
Cigarette smoking by women is associated with an increased risk for squamous cell carcinoma.[1,17,18] This risk increases with longer duration and intensity of smoking and may be present with exposure to environmental tobacco smoke, being as high as four times that of women who are nonsmokers and are not exposed to environmental smoking. Case-control studies of women infected with HPV have examined the effect of various types and levels of tobacco exposure and found similar results.[18,19]