Objectives: This study aimed to determine during 36 months of follow-up the (1) clinical outcomes and (2) influence of high-risk human papillomavirus (HPV) status on the risk of progression to cervical intraepithelial neoplasia 2+ (CIN 2+), among women with histologically proven CIN 1.
Materials and Methods: This is an ad hoc analysis of women with CIN 1 within TOMBOLA, a randomized trial of the management of women with low-grade cervical cytology. Women from the colposcopy arm with CIN 1 confirmed on punch biopsies and managed conservatively by cytology every 6 months in primary care were included. Sociodemographic data and a sample for HPV testing were collected at recruitment. Data on the sample women were extracted to calculate the cumulative incidence of CIN 2+ and the performance characteristics of the baseline HPV test. Detection of CIN 2 or worse (CIN 2+) during follow-up or at exit colposcopy was analyzed.
Results: A total of 171 women were included. Their median age was 29 years. Fifty-two percent were high-risk HPV positive, 17% were HPV-16 positive, and 11% were HPV-18 positive. Overall, 21 women (12%) developed CIN 2+, with a median time to detection of 25 months. Factors associated with progression to CIN 2+ were presence of HPV-18 (relative risk = 3.04; 95% CI = 1.09–8.44) and HPV-16 and/or HPV-18 at recruitment (relative risk = 3.98; 95% CI = 1.60–9.90). The sensitivity and specificity of a combined HPV-16/HPV-18 test for the detection of CIN 2+ during 3 years were 58% and 78%, respectively.
Conclusions: Our results suggest that women with confirmed CIN 1 have low rates of progression to high-grade CIN within 3 years. Because the median time to progression was 25 months, conservative management could recommend the next repeat cytology at 2 years.
Women with CIN 1 have a low rate of progression, and follow-up can be deferred for 2 years.
1Gynaecological Oncology, University Hospital of Llandough, Wales; and 2University of Aberdeen, Aberdeen, United Kingdom; 3National Cancer Registry Ireland, Cork, Ireland; 4Aberdeen Royal Infirmary, Aberdeen, United Kingdom; 5Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Canada; and 6Warwick Medical School, Coventry, United Kingdom
The authors have declared they have no conflicts of interest.
The work was supported by the Medical Research Council (G9700808) and the NHS in England and Scotland.
Institutions where study was carried out: Aberdeen, Nottingham, and Dundee in the United Kingdom.
Reprint requests to: Mahalakshmi Gurumurthy, University Hospital of Llandough, Penlan Rd, Penarth, CF64 2XX. E-mail: email@example.com
M.G. contributed in the critical review of the literature and writing of the article.
S.C. contributed in the collection and analysis of the data with statistical input and critical analysis of the article.
L.Sh. contributed in the analysis of the data, statistical input, and critical analysis of the article.
L.Sm. contributed in the critical analysis and writing of the article.
J.L. contributed in the data interpretation and critical revision of the manuscript.
N.W. provided comments on the drafts and was also the chief investigator for TOMBOLA 2003–2010.
M.E.C. conceived the original design, advised on the analysis and interpretation of the data, and wrote the article.
All authors approved the final version of the article.
Ethical approval was obtained from the Joint Research Ethics Committee of NHS Grampian and the University of Aberdeen (Reference 970072), the Tayside Committee on Medical Research Ethics (170/99) and the Nottingham Research Ethics Committee (PA129701).
Trial registration: ISRCTN 34841617 (http://www.isrctn.org/).