Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: A long-term multi-cohort study
ABSTRACT 15% of women treated for high-grade cervical intraepithelial neoplasia (CIN grade 2 or 3) develop residual or recurrent CIN grade 2 or 3 or cervical cancer, most of which are diagnosed within 2 years of treatment. To gain more insight into the long-term predictive value of different post-treatment strategies, we assessed the long-term cumulative risk of post-treatment CIN grade 2 or 3 or cancer and different follow-up algorithms to identify women at risk of residual or recurrent disease.
Women who were included in three studies in the Netherlands and who were treated for CIN grade 2 or 3 between July, 1988, and November, 2004, were followed up by cytology and testing for high-risk human papillomavirus (hrHPV) at 6, 12, and 24 months after treatment, and subsequently received cytological screening every 5 years. The primary endpoint was the cumulative risk of post-treatment CIN grade 2 or higher by December, 2009. We also assessed the cumulative risk of CIN grade 2 or higher in women with three consecutive negative cytological smears and women with negative co-testing with cytology and hrHPV at months 6 and 24. This study is registered in the Dutch trial register, NTR1468.
435 women were included, 76 (17%) of whom developed post-treatment CIN grade 2 or higher, of which 39 were CIN grade 3 or higher. The 5-year risk of developing post-treatment CIN grade 2 or higher was 16·5% (95% CI 13·0-20·7) and the 10-year risk was 18·3% (13·8-24·0). The 5-year risk of developing post-treatment CIN grade 3 or higher was 8·6% (95% CI 6·0-12·1) and the 10-year risk was 9·2% (5·8-14·2). Women with three consecutive negative cytological smears had a CIN grade 2 or higher risk of 2·9% (95% CI 1·2-7·1) in the next 5 years and of 5·2% (2·1-12·4) in the next 10 years. The 5-year risk of CIN grade 3 or higher was 0·7% (95% CI 0·0-3·9) and the 10-year risk was 0·7% (0·0-6·3). Women with negative results for co-testing had a 5-year risk of CIN grade 2 or higher of 1·0% (95% CI 0·2-4·6) and a 10-year risk of 3·6% (1·1-10·7). The 5-year risk of CIN grade 3 or higher was 0·0% (95% CI 0·0-3·0) and the 10-year risk was 0·0% (0·0-5·3).
The 5-year risk of post-treatment CIN grade 2 or higher in women with three consecutive negative cytological smears or negative co-testing for cytology and hrHPV at 6 and 24 months was similar to that of women with normal cytology in population-based screening and therefore justifies their return to regular screening.
VU University Medical Center, Erasmus University Medical Center, Netherlands.
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- "Evidence-based posttreatment followup consists of retesting at 24 months for women with a negative cotest at six months after treatment [15, 23]. "
ABSTRACT: Traditional population-based cervical screening programs, based on cytology, have successfully reduced the burden of cervical cancer. Nevertheless limitations remain and new screening methods are emerging. Despite vaccination against the 2 most oncogenic types (HPV 16/18), cervical cancer screening will have to continue as an essential public health strategy. As the acquisition of an HR-HPV infection is critical in the progression to (pre-)cancerous cervical lesions, recent research has focused on HR-HPV detection. The sensitivity of HPV testing in primary and secondary prevention outweighs that of cytology, at the cost of slightly lower specificity. Although most of the HR-HPV infections are cleared after conization, new evidence from numerous studies encourages the implementation of HR-HPV testing and genotyping to improve posttreatment surveillance. An HR-HPV test 6 months after conization is a promising useful clinical marker to detect persistence and prevent progression. This review highlights the clinical role of HPV testing in primary and secondary cervical cancer screening.Obstetrics and Gynecology International 07/2013; 2013:610373. DOI:10.1155/2013/610373
- Developmental Biology 08/2011; 356(1):220-221. DOI:10.1016/j.ydbio.2011.05.356 · 3.55 Impact Factor
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ABSTRACT: To evaluate testing for high-risk human papillomavirus (HR HPV) E6/E7 mRNA transcripts 6 months after conisation for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) to determine the risk of residual CIN2+. We prospectively followed 344 women treated for CIN2+ by conisation. HR HPV mRNA testing (PreTect HPV-Proofer, NorChip®), HR HPV DNA testing (AMPLICOR HPV Test, Roche Diagnostics®) and cytology was performed at 6 and 12 months after conisation. Biopsies were taken within 18 months of conisation if indicated by abnormal cytology, abnormal colposcopy, or positive HPV test. The LINEAR ARRAY HPV Genotyping Test (Roche Diagnostics®) was used to genotype cases with histologically confirmed residual disease diagnosed within 18 months after conisation. 6.4% (22/344) of study women had detected residual CIN2+. They were significantly older than those without residual CIN2+ (43.2 and 37.2 years respectively, p<0.001). Among women with detected residual CIN2+, 54.5% (12/22) had positive resection margins, 63.6% (14/22) had abnormal cytology, and 95.5% (21/22) had a positive HR HPV DNA test at 6 months. Sensitivity of HR HPV mRNA testing was 45.5% (95% confidence interval: 26.8-65.5%) at 6 months to predict detected residual CIN2+. Eight of 12 women who were HR HPV mRNA-negative at 6 months were HR HPV DNA-positive for one of the HPV types included in the mRNA test. Detection of E6/E7 mRNA transcripts by PreTect HPV Proofer does not seem suitable for short-term follow-up to detect residual CIN2+ after conisation.Gynecologic Oncology 08/2011; 123(2):257-62. DOI:10.1016/j.ygyno.2011.07.032 · 3.77 Impact Factor