ABSTRACT
Urine samples provide a potential alternative to physician-taken or self-collected cervical samples for cervical screening. Screening by primary hrHPV testing requires additional risk assessment (so-called triage) of hrHPV-positive women. Molecular markers, such as DNA methylation, have proven most valuable for triage when applied to cervical specimens. This study was set out to compare hrHPV and DNA methylation results in paired urine and cervical scrapes, and to evaluate the feasibility of DNA methylation analysis in urine to detect cervical cancer. Urine samples (n = 41; native and sediment) and paired cervical scrapes (n = 38) from cervical cancer patients, and urine from 44 female controls, were tested for hrHPV and 6 methylation markers. Results on native urine and sediment were highly comparable. A strong agreement was found between hrHPV testing on urine and scrapes (kappa = 0.79). Also, methylation levels in urine were moderately to strongly correlated to those detected in scrapes (r = 0.508-0.717). All markers were significantly increased in urine from cervical cancer patients compared to controls and showed a good discriminatory power for cervical cancer (AUC = 0.744-0.887). Our results show a good agreement of urine-based molecular analysis with reference cervical samples, and suggest that urine-based DNA methylation testing may provide a promising strategy for cervical cancer detection.
Subject(s)
Adenocarcinoma , Carcinoma, Adenosquamous , Carcinoma, Squamous Cell , DNA Methylation , Early Detection of Cancer/methods , Papillomaviridae/isolation & purification , Uterine Cervical Neoplasms , Adenocarcinoma/diagnosis , Adenocarcinoma/urine , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/urine , Carcinoma, Adenosquamous/diagnosis , Carcinoma, Adenosquamous/urine , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/urine , Cervix Uteri/metabolism , Cervix Uteri/pathology , Cervix Uteri/virology , Female , Humans , Mass Screening/methods , Middle Aged , Papillomavirus Infections/urine , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/urine , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/urineABSTRACT
AIMS: To examine long term survival of women with primary and recurrent cervical carcinoma in relation to (1) excretion of beta-core (a urinary metabolite of beta human chorionic gonadotrophin (beta hCG)) and (2) beta hCG immunostaining of the tumours, to determine the suitability of these markers for assessing prognosis. METHODS: This was a prospective observational study undertaken in a gynaecological oncology centre: 57 women with primary cervical cancer and 42 with recurrent disease were recruited between January 1990 and September 1992. Kaplan-Meier survival analysis with the log rank test was used to assess survival differences with survival rate given per year of follow up. RESULTS: In primary disease, the four year survival for the beta-core negative group was 79%, compared with 14% for the beta-core positive group (p = 0.001). This was still significant for early stage disease or squamous lesions alone. In recurrent disease, beta-core positivity was not prognostically significant. Immunohistochemistry was of no prognostic significance in either group. CONCLUSIONS: beta-core excretion appears to be useful in assessing prognosis of primary cervical cancer but not of recurrent disease. A large prospective study of urinary beta-core in early stage cervical cancer is needed to determine whether it can be used as an index for modifying treatment.