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Cancer. 2008 Nov 15;113(10 Suppl):2919-25. doi: 10.1002/cncr.23746.

Potential role of human papillomavirus in the development of subsequent primary in situ and invasive cancers among cervical cancer survivors.

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Arkansas Central Cancer Registry/Epidemiology Branch, Arkansas Department of Health, Little Rock, Arkansas, USA.



The recent licensure of human papillomavirus (HPV) vaccines will likely decrease the development of primary in situ and invasive cervical cancers and possibly other HPV-associated cancers such as vaginal, vulvar, and anal cancers. Because the HPV vaccine has the ability to impact the development of >1 HPV-associated cancer in the same individual, the risk of developing subsequent primary cancers among cervical cancer survivors was examined.


Using the 1992 through 2004 data from the Surveillance, Epidemiology, and End Results (SEER) program, 23,509 cervical cancer survivors were followed (mean of 4.8 person-years) for the development of subsequent primary cancers. The observed number (O) of subsequent cancers of all sites were compared with those expected (E) based on age-/race-/year-/site-specific rates in the SEER population. Standardized incidence ratios (SIRs = O/E) were considered statistically significant if they differed from 1, with an alpha level of 0.05.


Among cervical cancer index cases, there was a significant elevated risk for subsequent in situ cancers of the vagina and vulva (SIRs of 53.8 and 6.6, respectively); and invasive vaginal, vulvar, and rectal cancers (SIRs of 29.9, 5.7, and 2.2, respectively). Significantly elevated risks were observed across race and ethnic populations for subsequent vaginal in situ (SIR for whites of 49.4; blacks, 52.8; Asian/Pacific Islander [API], 91.4; and Hispanics, 55.7) and invasive cancers (SIR for whites of 25.7; blacks, 34.5; API, 48.5; and Hispanics, 25.2).


The results of the current study demonstrate a substantially increased risk of the development of subsequent primary in situ and invasive cancers among cervical cancer survivors and have implications for the development of prevention and early detection strategies as the role of HPV infection becomes evident.

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