Infection with an oncogenic type of HPV is etiologic for cervical cancer; however, such infection is common, and it is important to determine why only a subset of HPV-infected women develop cervical cancer. Differences between individuals in the development of, or the failure to repair, DNA damage may be involved in cervical carcinogenesis by influencing both the likelihood and the location of HPV integration into human DNA, or by otherwise influencing the occurrence and persistence of gene mutations. Assessing such differences between individuals represents an intriguing new avenue of cervical cancer research. The investigators propose to conduct an ancillary study within a currently funded population based case control study to evaluate whether constitutional genetic instability, as measured by lymphocyte bleomycin sensitivity, influences risk of invasive cervical cancer. Cases will be women aged 18-74 who are diagnosed with invasive cervical cancer from 1995-98. Controls will be similarly-aged women selected from the general population using RDD. Blood samples will be collected for measurement of lymphocyte bleomycin sensitivity as well as serologic evidence of HPV infection. In-person interviews will be conducted, and cervical cancer tissue will be collected to assess the presence of HPV DNA. Invasive cervical cancer is associated with substantial mortality. Identifying biomarkers of cervical cancer susceptibility may provide an important means of distinguishing women who are most likely to develop this disease. This knowledge may enable the development of therapeutic and preventive intervention strategies that are targeted to women at high risk. If women with cervical abnormalities who are at very low risk of disease progression can be identified, this may allow a reduction in the overtreatment of cervical disease that is currently believed to occur.
