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PDf file - 59K, Unadjusted risk ratios for CIN3+ vs

Background: Two currently available vaccines targeting human papillomavirus (HPV) types 16 and 18 could prevent 70% of cervical cancers and 50% of high-grade cervical lesions. Next-generation vaccines against additional types, such as a candidate 9-valent vaccine against HPV6/11/16/18/31/33/45/52/58, could further reduce HPV-associated disease burden.Methods: HPV was typed in archived tissues from women ages 21 to 39 years residing in five catchment areas in the United States with cervical intraepithelial neoplasia 2/3 and adenocarcinoma in situ (CIN2+) using L1 consensus PCR and type-specific hybridization. Type attribution was estimated using weights to account for lesions with multiple types detected.Results: From 2008 to 2011, 5,498 of 6,306 (87.2%) specimens obtained from 8,469 women with CIN2+ had valid typing results; HPV DNA was detected in 97.3%. Overall, 50.1% of lesions were attributable to HPV16/18, ranging from 50.3% to 52.4% among those ages 21 to 34 years, and significantly declined in 35 to 39 year-olds (43.5%). HPV16/18 attribution was higher in non-Hispanic whites (56.4%) versus racial/ethnic minorities (range, 41.8%–45.9%; P < 0.001). HPV31/33/45/52/58 attribution was 25.0% overall and increased with age (P < 0.001). A higher proportion of CIN2+ was attributable to HPV31/33/45/52/58 in non-Hispanic black (29.9%), Hispanic (29.2%), and Asian (33.1%) women compared with non-Hispanic whites (22.8%; P < 0.001).Conclusions: Overall, 75% of lesions were attributable to 7 oncogenic HPV types: 50% to HPV16/18 and 25% to HPV31/33/45/52/58. HPV16/18 had the largest attributable fraction in CIN2+ across all subpopulations, although to a lesser extent in older women and racial/ethnic minorities.Impact: Vaccines targeting additional oncogenic HPV types could prevent more high-grade cervical lesions, especially among racial/ethnic minorities. Cancer Epidemiol Biomarkers Prev; 24(2); 393–9. ©2014 AACR.

PDf file - 38K

Background: Recommendations for high-risk human papillomavirus (HR-HPV) testing as an adjunct to cytology for cervical cancer screening differ by age group, because HR-HPV tests lack adequate specificity in women aged Methods: Women ages 18 to 69 (n = 1,658) were enrolled and completed structured interviews to elicit data on behavioral risk factors prior to their examinations. HPV genotyping was done on exfoliated cervical cell samples. We estimated relative risks (RR) for HPV types and cofactors for CIN3+, overall and stratified by age group.Results: After 2 years of follow-up, we identified 178 CIN3+, 1,305 CIN0–2, and 175 indeterminate outcomes. Nonvaccine HR-HPV types were only associated with CIN3+ among women ≥30 (RR = 2.3, 95% CI: 1.5–3.4; Ptrend for increasing parity = 0.07). However, the parity association differed by age group (≥30: RR = 1.8, Ptrend = 0.008; Ptrend =.55).Conclusion: Subgroup variation by age in the risk of CIN3+ points to the importance of the timing of exposures in relation to CIN3+ detection.Impact: Future screening strategies need to consider natural history and secular trends in cofactor prevalence in the pursuit of appropriately sensitive and specific screening tools applied to appropriate age groups. Cancer Epidemiol Biomarkers Prev; 21(1); 111–21. ©2011 AACR.

Supplemental Table 1. Multivariable analysis of prevalence of HPV31/33/45/52/58-attributable CIN2+ lesions among women aged 18-39 years, HPV-IMPACT, 2008-2011

PDf file - 53K

Background: Two currently available vaccines targeting human papillomavirus (HPV) types 16 and 18 could prevent 70% of cervical cancers and 50% of high-grade cervical lesions. Next-generation vaccines against additional types, such as a candidate 9-valent vaccine against HPV6/11/16/18/31/33/45/52/58, could further reduce HPV-associated disease burden. Methods: HPV was typed in archived tissues from women ages 21 to 39 years residing in five catchment areas in the United States with cervical intraepithelial neoplasia 2/3 and adenocarcinoma in situ (CIN2+) using L1 consensus PCR and type-specific hybridization. Type attribution was estimated using weights to account for lesions with multiple types detected. Results: From 2008 to 2011, 5,498 of 6,306 (87.2%) specimens obtained from 8,469 women with CIN2+ had valid typing results; HPV DNA was detected in 97.3%. Overall, 50.1% of lesions were attributable to HPV16/18, ranging from 50.3% to 52.4% among those ages 21 to 34 years, and significantly declined in 35 to 39 year-olds (43.5%). HPV16/18 attribution was higher in non-Hispanic whites (56.4%) versus racial/ethnic minorities (range, 41.8%–45.9%; P < 0.001). HPV31/33/45/52/58 attribution was 25.0% overall and increased with age (P < 0.001). A higher proportion of CIN2+ was attributable to HPV31/33/45/52/58 in non-Hispanic black (29.9%), Hispanic (29.2%), and Asian (33.1%) women compared with non-Hispanic whites (22.8%; P < 0.001). Conclusions: Overall, 75% of lesions were attributable to 7 oncogenic HPV types: 50% to HPV16/18 and 25% to HPV31/33/45/52/58. HPV16/18 had the largest attributable fraction in CIN2+ across all subpopulations, although to a lesser extent in older women and racial/ethnic minorities. Impact: Vaccines targeting additional oncogenic HPV types could prevent more high-grade cervical lesions, especially among racial/ethnic minorities. Cancer Epidemiol Biomarkers Prev; 24(2); 393–9. ©2014 AACR.

Objective: Human papillomavirus (HPV) DNA testing combined with cytology (co-testing) has been recommended as a primary cervical cancer screening strategy and will be covered as a preventive service by the Affordable Care Act (ACA). Women with discordant results (HPV positive/cytology negative) present significant management challenges and result in additional costs due to follow-up visits and testing required. The frequency of discordant results in insured populations is at a level that does not negate the benefit of co-testing. However, it is unknown if the frequency of discordant results would be the same for underserved women, who may have more risk factors for HPV infection and cancer precursors. Methods: The Centers for Disease Control and Prevention's Cervical Cancer (Cx3) Study was conducted at 15 clinics in 6 Federally Qualified Health Centers (FQHCs) across Illinois. Providers at these clinics were given the option of co-testing for routine cervical cancer screening. Clinical high-risk HPV testing was performed using the FDA approved Hybrid Capture 2 assay (HC2: Qiagen). An additional research test to determine type-specific HPV results was performed on residual extracts. Results: Testing was completed on 2246 underserved women, mean age 45.1 years. The HPV test was positive in 7.2% and cytology abnormalities were detected in 6.0% with discordant results in 4.9% of women. The percentage of HPV positive tests decreased with age, from 10.3% among 30-39 year olds to 4.5% among 50-60 year olds. Among women with negative normal Pap test results who where high risk positive, 14% of the women were positive for HPV 16/18 while the remaining were positive for other high risk types. Conclusion: The rate of discordant co-testing in this study of underserved women was similar to those reported throughout the U.S. in different populations, including those who are insured. Similarly, the lower percentage of discordant results and those positive for HPV 16/18 may favor a more conservative management strategy than an aggressive strategy of immediate colposcopy. Citation Format: Mona Saraiya, Vicki Benard, April Greek, Martin Steinau, Sonya Patel, Diane Manninen, George Sawaya, Stuart Massad, Elizabeth Unger. HPV and Pap test results among low-income, underserved women: Providing insights into management strategies. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B92. doi:10.1158/1538-7755.DISP13-B92