Declines in human papillomavirus infection observed in the vaccine era
Authors: Mary Kay Barton
Journal: CA A Cancer Journal for Clinicians (2013)

Researchers have found a significant reduction in the prevalence of human papillomavirus (HPV) in female teenagers since the introduction of the HPV vaccine (J Infect Dis. 2013;208:385-393). Currently, 2 HPV vaccines are available: a quadrivalent vaccine against HPV types 6 (HPV-6), -11, -16, and -18; and a bivalent one against HPV-16 and -18. HPV-16 and -18 cause approximately 70% of cervical cancers and although HPV-6 and -11 are not oncogenic, they do cause anogenital warts and recurrent respiratory papillomatosis. According to the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, approximately 79 million Americans, most in their late teens and early 20s, are infected with HPV. Each year, about 14 million people become newly infected. CDC recommendations for vaccination with 3 doses of the quadrivalent vaccine for females aged 11 or 12 years, and catch-up vaccinations for those aged 13 to 26 years, were published in 2007. The bivalent vaccine was added to the recommendations after it became available in 2009. In 2011, the recommendation for the quadrivalent vaccine was expanded to include males. Researchers started to monitor HPV prevalence in the CDC's National Health and Nutrition Examination Survey (NHANES) in 2002, and in the current article, they compared national HPV prevalence in both the prevaccine and vaccine eras. Lauri Markowitz, MD, a medical epidemiologist at the CDC, and her colleagues analyzed NHANES data collected from 2003 to 2007. Because the vaccine was not introduced until late 2006, researchers considered data from 2003 through 2006 as the prevaccine era and data from 2007 to 2010 as the vaccine era. From 2003 to 2006, 5178 females aged 14 to 59 years were interviewed, 4150 of whom submitted a self-collected cervicovaginal swab that was adequate for HPV genotyping. From 2007 through 2010, 4988 females were interviewed and 4253 of them submitted a swab adequate for HPV genotyping. The data analysis included all women for whom HPV status could be determined. Results were grouped by age for those aged 14 to 19 years, 20 to 24 years, and 25 to 29 years, and the rest were grouped by decades. A significant difference in HPV infection between the prevaccine and vaccine eras was only observed in the group aged 14 to 19 years, which showed a much lower infection rate across all HPV types included in the vaccines: specifically, a 56% reduction in vaccine-type HPV (-6, -11, -16, and -18) and a 50% reduction in high-risk (HPV-16 and -18) alone. “This study shows that the U.S. HPV vaccination program is having an impact on the earliest HPV-related endpoint we can measure—vaccine-type infection,” says Dr. Markowitz, the study's lead author. “The vaccine appears to be very effective. This is not completely surprising as the HPV vaccine trials that were conducted before the vaccines were licensed found them [HPV vaccines] to have very high efficacy.” Paul Offit, MD, chief of the division of infectious diseases and director of the Vaccine Education Center at the University of Pennsylvania in Philadelphia, does think the findings are somewhat surprising, but in a good way. “The uptake of the HPV vaccine is fairly poor–in the 30% range–yet, despite the poor uptake, it [has] had a significant impact on HPV infection,” Dr. Offit notes. He says the HPV vaccine has a lower uptake than other vaccines even though the educational campaign about the importance of preventing HPV has been good. “The main issue is that this vaccine prevents a disease that can only be contracted by sexual activity,” he adds. “This is simply harder to address with parents and patients.” Further evaluation of the group aged 14 to 19 years was performed. In interviews conducted from 2007 through 2010, 34% of women reported receiving at least 1 dose of vaccine and approximately two-thirds of them received all 3 recommended vaccinations. A significant 88% decline in vaccine-type HPV was observed among sexually active vaccinated females during the period from 2007 to 2010 compared with 2003 to 2006. The unvaccinated group also had a decline in vaccine-type HPV infection of 28%, but this was not statistically significant, the report noted. Vaccine effectiveness of at least 1 dose was estimated to be 82%. There were no significant decreases in non–vaccine-type HPV infections, researchers determined. Dr. Markowitz and her colleagues examined other factors that could have accounted for a decrease in HPV infection, such as sexual behavior and race/ethnicity, but found that these were not significantly different between the 2 periods. In addition, there was no downward trend of HPV positivity observed in the time period approaching vaccine introduction, and there was no change in herpes simplex virus type 2 seroprevalence in the group aged 14 to 19 years between time periods. Researchers concluded that their data suggest an early impact of HPV vaccination, while conceding that other factors they did not measure could have contributed to the decreased HPV prevalence. “The major strength of NHANES is that it is a nationally representative study,” says Dr. Markowitz. “Some of the weaknesses of this study, such as self-reporting, that may have caused some misclassification of vaccine status, may be overcome by other vaccine-effectiveness studies that are being conducted that use provider-verified vaccine history and different outcomes and study designs.” Vaccine safety is always a big issue and obviously controversial. However, no serious safety concerns with the HPV vaccines have been identified to date. “NHANES is not designed to look at safety; however, there are other post-licensure safety monitoring systems that evaluate vaccine safety in the United States,” says Dr. Markowitz. These can be found on the CDC Web site (available at cdc.gov/vaccinesafety/Vaccines/HPV/Index.html). “The only safety issue has been fainting with the HPV vaccine,” Dr. Offit adds. “There is a false concern over safety issues.” In the current study, the decline in vaccine-type HPV infection was higher than expected and the authors note it could be due to herd immunity from vaccination, higher-than-anticipated effectiveness of administering fewer than the full 3-dose recommended vaccine course, or other unmeasured behavioral changes. Continued analysis is planned to examine the vaccine's impact on infection, the effectiveness of different numbers of vaccine doses, the potential cross-protection to non–vaccine-type HPV, and the duration of protection. “We have established that the vaccine is effective, now the key is to increase the uptake of vaccination in both females and males in order to increase the public health benefit observed,” Dr. Markowitz notes. The prevalence of human papillomavirus (HPV) infection among girls aged 14 to 19 years has declined since introduction of the HPV vaccine.