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RESEARCH: Sue Moss, Alastair Gray, Rosa Legood, Martin Vessey, Julietta Patnick, Henry Kitchener Liquid Based Cytology/Human Papillomavirus Cervical Pilot Studies Group Effect of testing for human papillomavirus as a triage during screening for cervical cancer: observational before and after study BMJ 2006; 332: 83-85 [Abstract] [Full text]

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High-risk human papillomavirus testing for women with borderline or mild dyskaryosis without increasing the colposcopy referral rate

Johannes Berkhof, Folkert J. van Kemenade, Peter J. Snijders, René H. Verheijen, Chris J. Meijer   (19 January 2006)

High-risk human papillomavirus testing for women with borderline or mild dyskaryosis without increasing the colposcopy referral rate 19 January 2006
Johannes Berkhof, Assistant Professor Dept. of Clin. Epidemiology and Biostatistics, VU University Medical Centre, 1007MB Amsterdam, Folkert J. van Kemenade, Peter J. Snijders, René H. Verheijen, Chris J. Meijer Send response to journal: Re: High-risk human papillomavirus testing for women with borderline or mild dyskaryosis without increasing the colposcopy referral rate	The persistence of high-risk human papillomavirus (HPV) infection is a prerequisite for the development of cervical cancer and warrants the use of adjunct HPV testing along cytology in cervical screening. Moss and colleagues1 show that colposcopy referral rates double if women with equivocal/mild cytological abnormality are referred for immediate colposcopy when HPV is present in the first abnormal smear. The colposcopy rates of Moss et al.1 for women of 35-64 years seem to contradict those observed in the Netherlands.   We computed colposcopy referral rates in the Netherlands with data collected in the two-armed POBASCAM screening trial2 et al. 2004). In that trial, women of 30-60 years with borderline/mild dyskaryosis were recalled at 6 and 18 months and referred for colposcopy on the basis of repeat cytology according to current Dutch guidelines (control group) or on the basis of both repeat cytology and high-risk HPV testing (intervention group). In the control group, 18.9% of all women with borderline dyskaryosis at baseline and 51.0% of those with mild dyskaryosis were eventually referred for colposcopy. After correction for loss to follow-up, we obtained adjusted colposcopy rates of 29.3% and 68.1% and rates of repeat smears per woman of 1.80 and 1.50 for women with borderline and mild dyskaryosis, respectively (see Table).   The tabulated colposcopy referral rates in the control group are twice as high as the before pilot referral rates presented by Moss and colleagues1 for women 35-64 years, whereas only a small increase in the rate of repeat smears is observed. Moreover, the colposcopy referral rates in the control and intervention group of the POBASCAM trial were very similar, indicating that HPV testing in the intervention group did not lead to increasing colposcopy rates.   The large difference in referral rates in the UK and the Netherlands for strategies with repeat cytology is not clear but may be partly explained by the difference in referral policy and follow-up period. Hence, comparability between the referral rates may improve when referral rates are reassessed after a longer follow-up.   On the basis of recent cost-effectiveness calculations3, we advise (A) to immediately return HPV-negative women with a borderline/mildly dyskaryotic smear to routine screening or (B) to manage women with a borderline/mildly dyskaryotic smear by repeat cytology and HPV testing at 6 and 18 months without HPV testing at baseline. Regarding strategy B, women that are negative on both tests at the first or second recall are immediately returned to routine screening. If we project strategy B on the POBASCAM data, colposcopy referral rates of 24.3% and 59.4% and repeat smear rates per woman of 1.08 and 1.17 are obtained in case of borderline and mild dyskaryosis, respectively. These data indicate that high-risk HPV testing can be implemented in triage policies for women with equivocal or mild cytological abnormalities in such a way that the number of repeat smears is markedly reduced without the cost of an increase in colposcopy referral rate.     Reference List   1.    Moss S, Gray A, Legood R, Vessey M, Patnick J, Kitchener H. Effect of testing for human papillomavirus as a triage during screening for cervical cancer: observational before and after study.  BMJ 2006;332:83-5. Notes: CORPORATE NAME: Liquid Based Cytology/Human Papillomavirus Cervical Pilot Studies Group. 2.    Bulkmans NW, Rozendaal L, Snijders PJ, Voorhorst FJ, Boeke AJ, Zandwijken GR et al. POBASCAM, a population-based randomized controlled trial for implementation of high-risk HPV testing in cervical screening: design, methods and baseline data of 44,102 women. Int J Cancer 2004;110:94-101. 3.    Berkhof J, de Bruijne MC, Zielinski GD, Bulkmans NW, Rozendaal L, Snijders PJ et al. Evaluation of cervical screening strategies with adjunct high-risk human papillomavirus testing for women with borderline or mild dyskaryosis. Int J Cancer 2005.     Smear results Adjusted rate of repeat smears per woman   Adjusted rate of referral to colposcopy (%)   Control group Intervention group   Control group Intervention  group Borderline 1.80 1.79   29.3 25.5 Mildly dyskaryotic 1.50 1.47   68.1 66.5         Competing interests: None declared