Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature.

BACKGROUND: Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical and other cancers. Our aim is to explore the risk of developing or dying from cervical cancer and other human papillomavirus (HPV)- and non-HPV-related malignancies after CIN treatment and infer its magnitude compared with the general population. MATERIALS AND METHODS: Design: Systematic review and meta-analysis. Eligibility criteria: Studies with registry-based follow-up reporting cancer incidence or mortality after CIN treatment. DATA SYNTHESIS: Summary effects were estimated using random-effects models. OUTCOMES: Incidence rate of cervical cancer among women treated for CIN (per 100 000 woman-years). Relative risk (RR) of cervical cancer, other HPV-related anogenital tract cancer (vagina, vulva, anus), any cancer, and mortality, for women treated for CIN versus the general population. RESULTS: Twenty-seven studies were eligible. The incidence rate for cervical cancer after CIN treatment was 39 per 100 000 woman-years (95% confidence interval 22-69). The RR of cervical cancer was elevated compared with the general population (3.30, 2.57-4.24; P < 0.001). The RR was higher for women more than 50 years old and remained elevated for at least 20 years after treatment. The RR of vaginal (10.84, 5.58-21.10; P < 0.001), vulvar (3.34, 2.39-4.67; P < 0.001), and anal cancer (5.11, 2.73-9.55; P < 0.001) was also higher. Mortality from cervical/vaginal cancer was elevated, but our estimate was more uncertain (RR 5.04, 0.69-36.94; P = 0.073). CONCLUSIONS: Women treated for CIN have a considerably higher risk to be later diagnosed with cervical and other HPV-related cancers compared with the general population. The higher risk of cervical cancer lasts for at least 20 years after treatment and is higher for women more than 50 years of age. Prolonged follow-up beyond the last screening round may be warranted for previously treated women.

Serum antibody response to Chlamydia trachomatis TroA and HtrA in women with tubal factor infertility.

Persistent genital chlamydial infection may lead to tubal factor infertility (TFI). Chlamydia trachomatis TroA and HtrA are proteins expressed during persistent chlamydial infection in vitro. We studied serum IgG antibody response against these proteins by EIA in women with TFI and in subfertile women without tubal pathology. Altogether, 22 of 258 subfertile women (8.5%) had TFI which was unilateral in 17 cases and bilateral in 5 cases. Overall, 55 (21.3%) of the 258 women had TroA and 39 (15.1%) had HtrA antibodies. Seropositivity to TroA and HtrA was more common among women with TFI than women with other causes for subfertility (45.5 vs. 19.1%, p = 0.004 for TroA; 36.4 vs. 13.1%, p = 0.004 for HtrA). Mean absorbance values and the prevalence of TroA and HtrA antibodies increased with increasing severity of TFI. On the basis of our results, TroA and HtrA serology has the potential to be further developed to a specific biomarker for C. trachomatis-related TFI.

Pregnancy incidence and outcome among patients with cervical intraepithelial neoplasia: a retrospective cohort study.

OBJECTIVE: To investigate the effect of cervical intraepithelial neoplasia (CIN) treatment on incidence of pregnancy and pregnancy outcome. DESIGN: Retrospective cohort study. SETTING: Helsinki University Central Hospital, Finland, the sole reference centre in the Helsinki-Uusimaa region for women referred for colposcopy. POPULATION: A cohort of 6179 women treated for CIN between 1974 and 2001, and a randomly selected, age- and municipality-matched, reference population of 30,436 women. METHODS: Based on nationwide registers, all women were followed-up for pregnancy outcomes until death, emigration, sterilization, or until the end of 2004. MAIN OUTCOME MEASURES: Incidence of any pregnancy, livebirths, miscarriages, extrauterine pregnancies, molar pregnancies, and terminations of pregnancies (TOPs) before and after CIN treatment, estimated by calculating hazard ratios (HRs) with stratified Cox regression and Poisson regression. RESULTS: After CIN treatment, both incidence of pregnancy (HR 1.20; 95% CI 1.15-1.26; P < 0.001) and incidence of livebirths (HR 1.12; 95% CI 1.06-1.18; P < 0.001) were higher among the treated women than among the reference population. Before treatment, only incidence of pregnancy had been elevated among those treated (HR 1.06; 95% CI 1.04-1.09; P < 0.001). The incidence of extrauterine pregnancies and of TOPs was significantly elevated among those treated both before and after CIN treatment. CONCLUSIONS: No clear evidence emerged of adverse effects resulting from the CIN treatment itself, because the women treated had more pregnancies and more children than their reference population. TOPs and extrauterine pregnancies were more common among the treated women already before the CIN treatment.