title: High-risk HPV testing in women with borderline and mild dyskaryosis: long-term follow-up data and clinical relevance.
abstract: In The Netherlands and most other European countries, women with two serial cervical smears with borderline or mild dyskaryosis (BMD) within 6 months are referred for colposcopy-directed biopsies. Only about 10% of these women have high-grade cervical intraepithelial neoplasia (CIN). This study therefore investigated whether human papillomavirus (HPV) testing could identify which women with smears read as BMD are most likely to have high-grade CIN, either at referral or during follow-up and the relationship was determined between clearance of high-risk HPV and regression of abnormal cytology. Women with smears read as BMD (n=278) were referred to the gynaecologist for colposcopy. They were subdivided into two groups; group A comprised women with a single smear (n=172) and group B women with two sequential smears (n=106) read as BMD before referral. High-risk HPV detection with Hybrid Capture II (HC II) was performed on a cervical scrape taken at the first visit before colposcopy (i.e. baseline smear) and during follow-up. Biopsies were taken when lesions suspected for CIN were seen at colposcopy. High-risk HPV DNA was present in the baseline smears of 126 (45.0%) women; 26 (20.6%) of them had histologically confirmed CIN 2/3 at the first visit and another 14 (11.1%) during follow-up. Only one of the 152 women (0.7%) with a negative high-risk HPV test had a CIN 2 lesion at the first visit and no CIN lesions were detected during follow-up of these women. After exclusion of women who were treated for prevalent high-grade CIN, the median follow-up times were 1.3 years (range 0.0-4.3 years) and 1.6 years (range 0.0-4.5 years) for women with HPV-negative and HPV-positive baseline smears, respectively. The sensitivity of a positive high-risk HPV test for CIN 2/3 at the first visit was 96.3%, the specificity 60.2%, the positive predictive value 20.6%, and the negative predictive value 99.3%. These values did not change markedly when stratified for group A or group B. Thus, a high-risk HPV positive test was strongly associated with the presence at the first visit and the development of CIN 2/3 lesions during follow-up. Moreover, regression of abnormal cytology in women with a positive high-risk HPV test at baseline was strongly associated with viral clearance and occurred 0.3 years (range -1.2 to 1.7 years) later than HPV clearance. This study establishes the value of a high-risk HPV positive test for women at risk of high-grade CIN, with virtually no risk for missing CIN 2/3. Addition of a test on high-risk HPV in women with BMD could prevent 55% of the referrals and/or repeat smears.
authors.affiliation: Department of Pathology, University Hospital Vrije Universiteit, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Denise Zielinski
authors.forename: P J
authors.initials: PJ
authors.lastname: Snijders
authors.forename: L
authors.initials: L
authors.lastname: Rozendaal
authors.forename: F J
authors.initials: FJ
authors.lastname: Voorhorst
authors.forename: A P
authors.initials: AP
authors.lastname: Runsink
authors.forename: F A
authors.initials: FA
authors.lastname: de Schipper
authors.forename: C J
authors.initials: CJ
authors.lastname: Meijer
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D002584:Cervix Uteri / Q000473:pathology / Q000821:virology*; D016009:Chi-Square Distribution; D003127:Colposcopy; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000188:drug therapy; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012017:Referral and Consultation; D012306:Risk; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D014626:Vaginal Smears / Q000706:statistics & numerical data; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral