ABSTRACT
INTRODUCTION: Recent studies have shown that CADM1/MAL-methylation testing detects high-grade CIN lesions with a high short-term progression risk for cervical cancer. Women treated for CIN2/3 are at risk of post-treatment disease, representing either persistent (incompletely treated) or incident (early onset) lesions. Here, we evaluated CADM1/MAL-methylation analysis as potential tool for detecting recurrent high-grade CIN lesions (rCIN2/3). METHODS AND MATERIALS: A multicenter prospective clinical cohort study was conducted among 364 women treated for CIN2/3. Cervical scrapes were taken prior to treatment, and six and 12months post-treatment and tested for cytology, hrHPV (plus genotype) and CADM1/MAL-methylation. When at six months either of these tests was positive, a colposcopy-directed biopsy was obtained. At 12months, all women underwent an exit-colposcopy with biopsy. In case of rCIN2/3, re-treatment was done. RESULTS: We found 28 rCIN2 (7.7%) and 14 rCIN3 (3.8%), resulting in a total recurrence rate of 11.5%. All 14 women with rCIN3 and 15/28 (54%) with rCIN2 showed hrHPV type-persistence. Of these, 9/14 (64%) rCIN3 and 8/15 (53%) rCIN2 were CADM1/MAL-methylation positive. All incident rCIN2, characterized by hrHPV genotype-switch, were CADM1/MAL-methylation negative. All three carcinomas found after re-treatment were CADM1/MAL-methylation positive. CADM1/MAL-methylation positivity at both baseline and follow-up significantly increased the risk of ≥rCIN3 (from 0.7% to 18.4%), and ≥rCIN2 (from 8.2% to 36.8%), compared to a consistently CADM1/MAL-methylation negative result (p-value: <0.001). CONCLUSION: Post-treatment monitoring by CADM1/MAL-methylation analysis identifies women with an increased risk of rCIN2/3. Our results confirm previous data indicating that CADM1/MAL-methylation analysis provides a high reassurance against cancer.
Subject(s)
Cell Adhesion Molecules/genetics , DNA Methylation , Immunoglobulins/genetics , Myelin and Lymphocyte-Associated Proteolipid Proteins/genetics , Uterine Cervical Dysplasia/genetics , Uterine Cervical Neoplasms/genetics , Adult , Cell Adhesion Molecule-1 , Female , Humans , Middle Aged , Prospective StudiesABSTRACT
OBJECTIVE: To investigate the agreement between conventional colposcopic impression, dynamic spectral imaging (DSI) colposcopy and histology, for human papillomavirus type 16-positive (HPV16(+)) and non-16 high-risk (hr) HPV(+) women. DESIGN: Prospective, comparative, multicentre clinical trial. SETTING: Three colposcopy clinics in the Netherlands. POPULATION: Women (n = 177) aged 18 years or over with an intact cervix, referred for colposcopy. METHODS: The colposcopist graded the lesion by using the DSI colposcope as a regular video colposcope. Subsequently the DSI impression was displayed and biopsies were taken from all abnormal areas as well as from a random (normal) site. A cervical smear was taken for HPV typing. MAIN OUTCOME MEASURES: Histologically confirmed high-grade cervical intraepithelial neoplasia or cancer (CIN2(+)), positive for HPV16 or for any other hrHPV type. RESULTS: The DSI colposcope identified more CIN2(+) cervical lesions among HPV16(+) women than in non-16 hrHPV(+) women (P = 0.032 regardless of final histology and P = 0.009 among women with CIN2(+)). Consequently, the sensitivity of the DSI colposcope for detecting CIN2(+) lesions was higher in HPV16(+) women than in non-16 hrHPV(+) women (97% versus 74%, P = 0.009). No such differences were seen for the colposcopist impression. In addition, mainly smaller cervical lesions are missed by the colposcopist. CONCLUSIONS: The sensitivity of DSI colposcopy for CIN2(+) is higher in HPV16(+) than in non-16 hrHPV(+) women. Furthermore, regardless of HPV16 status, the sensitivity of DSI for CIN2(+) is higher than that of the colposcopist, probably because colposcopists tend to miss smaller cervical lesions.