Monitoring Effect of Human Papillomavirus Vaccines in US Population, Emerging Infections Program, 2008-2012.

In 2007, five Emerging Infections Program (EIP) sites were funded to determine the feasibility of establishing a population-based surveillance system for monitoring the effect of human papillomavirus (HPV) vaccine on pre-invasive cervical lesions. The project involved active population-based surveillance of cervical intraepithelial neoplasia grades 2 and 3 and adenocarcinoma in situ as well as associated HPV types in women >18 years of age residing in defined catchment areas; collecting relevant clinical information and detailed HPV vaccination histories for women 18-39 years of age; and estimating the annual rate of cervical cancer screening among the catchment area population. The first few years of the project provided key information, including data on HPV type distribution, before expected effect of vaccine introduction. The project's success exemplifies the flexibility of EIP's network to expand core activities to include emerging surveillance needs beyond acute infectious diseases. Project results contribute key information regarding the impact of HPV vaccination in the United States.

Reduction in HPV 16/18-associated high grade cervical lesions following HPV vaccine introduction in the United States - 2008-2012.

BACKGROUND: Prevention of pre-invasive cervical lesions is an important benefit of HPV vaccines, but demonstrating impact on these lesions is impeded by changes in cervical cancer screening. Monitoring vaccine-types associated with lesions can help distinguish vaccine impact from screening effects. We examined trends in prevalence of HPV 16/18 types detected in cervical intraepithelial neoplasia 2, 3, and adenocarcinoma in situ (CIN2+) among women diagnosed with CIN2+ from 2008 to 2012 by vaccination status. We estimated vaccine effectiveness against HPV 16/18-attributable CIN2+ among women who received ≥1 dose by increasing time intervals between date of first vaccination and the screening test that led to detection of CIN2+ lesion. METHODS: Data are from a population-based sentinel surveillance system to monitor HPV vaccine impact on type-specific CIN2+ among adult female residents of five catchment areas in California, Connecticut, New York, Oregon, and Tennessee. Vaccination and cervical cancer screening information was retrieved. Archived diagnostic specimens were obtained from reporting laboratories for HPV DNA typing. RESULTS: From 2008 to 2012, prevalence of HPV 16/18 in CIN2+ lesions statistically significantly decreased from 53.6% to 28.4% among women who received at least one dose (Ptrend<.001) but not among unvaccinated women (57.1% vs 52.5%; Ptrend=.08) or women with unknown vaccination status (55.0% vs 50.5%; Ptrend=.71). Estimated vaccine effectiveness for prevention of HPV 16/18-attributable CIN2+ was 21% (95% CI: 1-37), 49% (95% CI: 28-64), and 72% (95% CI: 45-86) in women who initiated vaccination 25-36 months, 37-48 months, and >48 months prior to the screening test that led to CIN2+ diagnosis. CONCLUSIONS: Population-based data from the United States indicate significant reductions in CIN2+ lesions attributable to types targeted by the vaccines and increasing HPV vaccine effectiveness with increasing interval between first vaccination and earliest detection of cervical disease.

Interactive effects of individual and neighborhood race and ethnicity on rates of high-grade cervical lesions.

We estimated the main and interactive effects of individual race/ethnicity (black, Hispanic, white) and area race, ethnicity, and poverty (proportions of the female population black, Hispanic, and living below the federal poverty level at the census tract level, respectively) on rates of high-grade cervical lesions among young women. Using data from a statewide surveillance system during 2008-2011, we found a marginally significant interaction (P<0.05) between individual race/ethnicity and area race, with black and Hispanic women living in areas with ≥20% of the female population black having elevated rates compared to those living in areas with <20% of the female population black. These findings indicate a possible synergistic effect between individual race/ethnicity and racial composition in neighborhoods on precancerous cervical lesions.

Sources of information for assessing human papillomavirus vaccination history among young women.

Assessing history of human papillomavirus (HPV) vaccination is important for monitoring vaccine uptake, impact, and effectiveness. Based on data collected from 1720 women with high-grade cervical lesions reported to a statewide surveillance system in Connecticut, we found that available medical records did not contain HPV vaccination information for 34% of women, and 43% of women could not be reached for interview. When both were used for data collection, concordance of vaccination history (83%) and sensitivity of self-report (96%) were both high. Reviewing medical records based on self-reported information about vaccine providers increased confirmation of vaccination histories in this sample by 18%. The vaccine registry in Connecticut is not currently utilized for HPV vaccinations, but efforts to increase use for adolescent vaccines could be useful in the future to overcome limitations of other sources.

Individual and geographic disparities in human papillomavirus types 16/18 in high-grade cervical lesions: Associations with race, ethnicity, and poverty.

BACKGROUND: Current vaccines protect against 2 human papillomavirus (HPV) types, HPV 16 and 18, which are associated with 70% of cervical cancers and 50% of high-grade cervical lesions. HPV type distribution was examined among women with high-grade lesions by individual and area-based measures of race, ethnicity, and poverty. METHODS: This analysis included 832 women aged 18 to 39 years reported to a surveillance registry in Connecticut during 2008 to 2010. Diagnostic specimens were obtained for HPV DNA testing. Individual measures were obtained from surveillance reports, medical records, and patient interviews. Cases were geocoded to census tracts and linked to area-based measures of race, ethnicity, and poverty. Statistical analysis included use of generalized estimating equations. RESULTS: Overall, 44.8% of women had HPV 16/18. In a multivariate model controlled for confounding by age and diagnosis grade, black race (adjusted prevalence ratio [aPR] = 0.54, 95% confidence interval [CI] = 0.34-0.88), Hispanic ethnicity (aPR = 0.59, 95% CI = 0.40-0.88), and higher area-based poverty (aPR = 0.59, 95% CI = 0.40-0.87) were associated with a lower likelihood of HPV 16/18 positivity. Black and Hispanic women were less likely to have HPV 16/18 than white women across all levels of area-based measures. CONCLUSIONS: Black race, Hispanic ethnicity, and higher area-based poverty are salient predictors of lower HPV 16/18 positivity among women with high-grade cervical lesions. These data suggest that HPV vaccines might have lower impact among black and Hispanic women and those living in high poverty areas. These findings have implications for vaccine impact monitoring, vaccination programs, and new vaccine development.

Declining rates of high-grade cervical lesions in young women in Connecticut, 2008-2011.

Vaccines that prevent infection with human papillomavirus (HPV) types 16 and 18 that are known to cause cervical cancer have been available in the United States since 2006. High-grade cervical lesions are important for monitoring early vaccine impact because they are strong surrogates for cancer yet can develop within years after infection as opposed to decades. Trends in high-grade cervical lesions including cervical intraepithelial neoplasia grades 2, 2/3, and 3 and adenocarcinoma in situ among women ages 21 to 39 years old were examined using a statewide surveillance registry in Connecticut from 2008 to 2011. During this time period, HPV vaccine initiation increased among adolescent females from 45% to 61%. Analyses were stratified by age, according to census tract measures of proportion of population Black, Hispanic, living in poverty, and by urban/nonurban counties. The annual rate per 100,000 females ages 21 to 24 years declined from 834 in 2008 to 688 in 2011 (P(trend) < 0.001). No significant declines were observed among women ages 25 to 39 years. Significant declining trends also occurred in census tracts with lower proportions of the population being Black, Hispanic, or living below the federal poverty level. Declines in high-grade cervical lesions have occurred among young women during 2008 to 2011. This is the first report of declines in cervical neoplasia in the United States since HPV vaccines became available. Continued surveillance is needed to measure vaccine impact and monitor health disparities.

Geographic poverty and racial/ethnic disparities in cervical cancer precursor rates in Connecticut, 2008-2009.

OBJECTIVES: We examined associations of geographic measures of poverty, race, ethnicity, and city status with rates of cervical intraepithelial neoplasia grade 2 or higher and adenocarcinoma in situ (CIN2+/AIS), known precursors to cervical cancer. METHODS: We identified 3937 cases of CIN2+/AIS among women aged 20 to 39 years in statewide surveillance data from Connecticut for 2008 to 2009. We geocoded cases to census tracts and used census data to calculate overall and age-specific rates. Poisson regression determined whether rates differed by geographic measures. RESULTS: The average annual rate of CIN2+/AIS was 417.6 per 100,000 women. Overall, higher rates of CIN2+/AIS were associated with higher levels of poverty and higher proportions of Black residents. Poverty was the strongest and most consistently associated measure. However, among women aged 20 to 24 years, we observed inverse associations between poverty and CIN2+/AIS rates. CONCLUSIONS: Disparities in cervical cancer precursors exist for poverty and race, but these effects are age dependent. This information is necessary to monitor human papillomavirus vaccine impact and target vaccination strategies.

Human papillomavirus vaccination history among women with precancerous cervical lesions: disparities and barriers.

OBJECTIVE: To estimate racial, ethnic, and socioeconomic differences in human papillomavirus (HPV) vaccination history among women aged 18-27 years with precancerous cervical lesions diagnosed, barriers to vaccination, and timing of vaccination in relation to the abnormal cytology result that preceded the diagnosis of the cervical lesion. METHODS: High-grade cervical lesions are reportable conditions in Connecticut for public health surveillance. Telephone interviews and medical record reviews were conducted during 2008-2010 for women (n=269) identified through the surveillance registry. RESULTS: Overall, 43% of women reported history of one or more doses of HPV vaccine. The mean age at vaccination was 22 years. Publicly insured (77%) and uninsured (85%) women were more likely than privately insured women (48%) to report no history of vaccination (P<.05). Among unvaccinated women, being unaware of HPV vaccine was reported significantly more often among Hispanics than non-Hispanics (31% compared with 13%, P=.02) and among those with public or no insurance compared with those with private insurance (26% and 36% compared with 6%, P<.05 for both). The most commonly reported barrier was lack of provider recommendation (25%). Not having talked to a provider about vaccine was reported significantly more often among those with public compared with private insurance (41% compared with 18%, P<.001). Approximately 35% of women received vaccine after an abnormal cytology result; this occurred more frequently among African American women compared with white women (80% compared with 30%, P<.01). CONCLUSION: Catch-up vaccination strategies should focus on provider efforts to increase timely coverage among low-income and minority women.