Molecular and epidemiological study of adenocarcinoma of the cervix : a population-based study
Organised cervical cytology screening has successfully reduced the: incidence of squamous cervical cancer, leading to a relative increase in the incidence of adenocarcinoma of the cervix (ACC). Human Papillomavirus (HPV) infection is a necessary but not sole factor in the development of cervical cancer. This molecular epidemiological study is aimed at identifying the viral specific and host specific biological and behavioural co-factors. I have coupled two powerful techniques, laser capture microdissection and real-time quantitative PCR to determine the HPVI6 prevalence in the women with ACC, compared to age-matched controls, and to accurately assess the HPV16 DNA copy number in the cells. A case control study was also conducted to identify biological and behavioural risk factors, including cervical cytology screening history. The key finding of this study is the confirmation of HPV 16 infection in the cervical adenocarcinoma cells. The prevalence of HPV 16 infection in this cohort of women with ACC diagnosed in years 1991-2000 was 24%. Women with ACC were more likely to have HPV 16 infection than the age-matched control group (χ2, p=0.014). The HPV 16 DNA copy number per cell was also significantly higher in the women with ACC than in the control group (χ2, p<0.0001). The HPV 16 DNA copy number per cell was significantly higher in the women >45 years in this cohort. Women with ACC were less likely to attend for cervical cytology screening compared to the control group (conditional logistic regression; χ2, p<0.00001). Sixty-three percent of the index cervical smears demonstrated glandular abnormalities compared to 26% squamous abnormalities. This could be a reflection of the local cytologists' ability to recognise glandular cytological changes, further increasing the protective effect of regular attendance of cervical cytological screening.