The quadrivalent vaccine prevents HPV-6 and -11 infections that cause genital warts. The clinical trials for women show a 99% efficacy in protection from HPV-6, -11, -16, and -18 caused external warts in women who received all three of the vaccine shots and 80% of those who did not (36). In the vaccine trials in men and boys the protection was 89% at 29 months, leading to approval of this quadrivalent vaccine in males (37).
The quadrivalent vaccine trials evaluated the protection from vulva intraepithelial neoplasia (VIN) and vaginal intraepithelial neoplasia (VAIN). The women who were HPV negative at vaccination and followed the protocol had a 100% reduction in HPV-16, -18 caused VIN 2 or 3, and VAIN 2 or 3 lesions compared to placebo (38). When the entire vaccinated population was evaluated, the reduction in VIN 2 or 3 and VAIN 2 or 3 was 50% (38). These data demonstrate that high-risk HPV types other than 16 and 18 are responsible for a significant proportion of VIN and VAIN. It reveals that women who were already positive for HPV-16 and -18 were not protected from VIN and VAIN. The bivalent trials were not designed to assess vulvar or vaginal end points.
Duration of vaccine efficacy is important because we know that HPV infection peaks in the early 20s and cervical cancer occurs in the 40s. The vaccines are approved for women up to 26 years of age and to be protective they should be effective beyond 10 years. In order to induce a significant antibody response to the antigen, it is combined with an adjuvant. The quadrivalent adjuvant is aluminum hydroxyphosphate sulfate, which proved to be superior to a simple aluminum adjuvant in binding to HPV-16 in mice. By contrast, the bivalent adjuvant is an aluminum hydroxide combined with a monophosphoryl lipid A. This is theorized to function as a link between the HPV and the activation of the innate immune system. This adjuvant produced higher antibody titers than aluminum-induced titers at the 4-year follow-up visit (39). It remains unclear whether a booster shot will be needed as the adolescent cohort reaches its mid-20s where the exposure to HPV peaks. Because the first vaccinations were given less than 10 years ago, the studies to determine the advisability of a booster are ongoing.
The American Committee on Immunization Practices developed recommendations for the utilization of both the quadrivalent and bivalent vaccines in young girls and women. In 2007 the American Cancer Society issued a set of clinical guidelines that remain relevant to the use of these agents (40). Under these guidelines, routine HPV vaccination is recommended for girls at 11 to 12 years of age, but may be provided as early as 9 years and as late as 18 years. For young women between the ages of 19 to 26, there are insufficient data to determine the value of universal vaccination. A decision to vaccinate a woman in that age group should be based on an informed discussion with her health care provider regarding her risk of previous HPV exposure and potential benefit and harm from the vaccination (41–44). Screening practices for cervical intraepithelial neoplasia and cancer should remain unchanged in both vaccinated and unvaccinated women.
Pap Test Classification: In 1988, the first National Cancer Institute (NCI) workshop held in Bethesda, Maryland, resulted The Bethesda System in the development of the Bethesda System for cytologic reporting (45). A standardized method of reporting cytology findings facilitated peer review and quality assurance. The terminology
Table 19.1 Comparison of Cytology Classification Systems