HPV Vaccination Decreases High-Grade Cervical Lesions in Women

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Investigators recommend continued surveillance to determine whether the observed increased rates in the largely unvaccinated older age groups represent a shift in age at diagnosis.
Investigators recommend continued surveillance to determine whether the observed increased rates in the largely unvaccinated older age groups represent a shift in age at diagnosis.

From 2008 to 2015, both cervical intraepithelial neoplasia (CIN) grades 2, 3 and adenocarcinoma in situ (CIN2+) rates and rates of cervical cancer screening declined in women age 18 to 24 years, which is consistent with the population-level impact of the human papillomavirus (HPV) vaccination, according to a study recently published in Clinical Infectious Diseases.

In the United States, HPV vaccination has been recommended for adolescent females age 11 to 12 years since 2006. Uptake of the vaccine has been gradual, but nationally, the proportion of women age 19 to 26 years who received at least 1 dose of HPV vaccine increased from 10.5% in 2008 to 40.2% in 2014. However, the impact of the vaccination program on HPV-associated cancers may not be observed for decades given the long natural history of HPV infection and carcinogenesis. Additionally, since introducing the HPV vaccine, cervical cancer screening recommendations have changed multiple times, complicating interpretation of population trends in cervical precancers. For example, in 2012 the recommendation was to delay initial screening to 21 years and have longer intervals of 3 years between screenings. Thus, it is difficult to determine whether decreases in rates of cervical lesions in the population represent vaccine impact or the results of fewer women receiving annual screening. Therefore, this study described changes in rates of CIN2+ during a period of HPV vaccine uptake and changing cervical cancer screening recommendations.

A total of 16,572 CIN2+ cases were included after a population-based laboratory surveillance for CIN2+ in 5 states from 2008 to 2015 via the HPV Vaccine Impact Monitoring Project, a network of surveillance sites that consists of partnerships among the Centers for Disease Control and Prevention, state health departments, and academic institutions. Surveillance sites included California, Connecticut, New York, Oregon, and Tennessee. Each site used local laboratory or administrative data to estimate the annual proportion of the population diagnosed with cervical cancer. Population-based CIN2+ rates per 100,000 women categorized by age group (18-20, 21-24, 25-29, 30-34, and 35-39 years) were calculated and incidence rate ratios (IRR) of CIN2+ for 2-year periods were estimated among all women and in the estimated screened population to evaluate changes over time.

Among women age 18 to 20 and 21 to 24 years, CIN2+ rates declined in all 5 sites, whereas in women age 25 to 29, 30 to 34, and 35 to 39 years, trends differed across sites. Further, the percent of women screened annually declined in all sites and all age groups. When compared with 2008 to 2009, rates among screened women were significantly lower for all 3 periods in women age 18 to 20 years (2010-2011: IRR= .82; 2012-2013: IRR= 0.63; 2014-2015: IRR= .44) and lower for the latter 2 time periods in women age 21 to 24 years (2012-2013: IRR= .86; 2014-2015: IRR= .61). Rates among screened women increased for age groups 25 to 29 years, 30 to 34 years, and 35 to 39 years. This increased yield of CIN2+ per screening episode and older age at initial diagnosis is an expected result because of changes in screening and management recommendations, including delayed age at first screen, conservative management of young women, increased length of screening intervals, and incorporating clinical HPV testing into screening algorithms.

Overall, the study authors concluded that, “[T]his analysis of eight years of active population-based laboratory surveillance data for high-grade cervical lesions is consistent with vaccine impact in young women ages 18-20 and 21-24 years.”

Reference

Gargano JW, Park IU, Griffin MR, et al. Trends in high-grade cervical lesions and cervical cancer screening in five states, 2008-2015 [published online August 23, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy707

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