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Open Access Research article

Prediction of cervical intraepithelial neoplasia grade 2+ (CIN2+) using HPV DNA testing after a diagnosis of atypical squamous cell of undetermined significance (ASC-US) in Catalonia, Spain

Raquel Ibáñez1, Judit Moreno-Crespi2, Montserrat Sardà3, Josefina Autonell3, Montserrat Fibla4, Cristina Gutiérrez5, Belen Lloveras6, María Alejo7, Isabel Català8, Francesc Alameda106, Miquel Casas2, F Xavier Bosch1 and Silvia de Sanjosé19*

Author Affiliations

1 Unit of Infections and Cancer. Cancer Epidemiology Research Programme, IDIBELL. Catalan Institute of Oncology, Av. Gran Vía, 199-203L'Hospitalet de Llobregat, 08907 Barcelona, Spain

2 Pathology Department, University Hospital of Girona Dr. Josep Trueta, Catalan Institute of Oncology, Girona, Spain

3 Pathology Department, Hospital Consortium of Vic, Barcelona, Spain

4 Pathology Department, University Hospital of Tarragona Joan XXIII, Tarragona, Spain

5 Clinical Laboratory ICS Tarragona, Molecular Biology Section University Hospital of Tarragona Joan XXIII IISPV, Rovira i Virgili University, Tarragona, Spain

6 Pathology Department, Hospital del Mar, Barcelona, Spain

7 Pathology Department, L'Hospitalet General Hospital, Barcelona, Spain

8 Pathology Department, Bellvitge University Hospital, Barcelona, Spain

9 CIBER Epidemiologia y Salud Pública, Madrid, Spain

10 Universitat de Barcelona, Barcelona, Spain

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BMC Infectious Diseases 2012, 12:25  doi:10.1186/1471-2334-12-25

Published: 26 January 2012

Abstract

Background

A protocol for cervical cancer screening among sexually active women 25 to 65 years of age was introduced in 2006 in Catalonia, Spain to increase coverage and to recommend a 3-year-interval between screening cytology. In addition, Human Papillomavirus (HPV) was offered as a triage test for women with a diagnosis of atypical squamous cells of undetermined significance (ASC-US). HPV testing was recommended within 3 months of ASC-US diagnosis. According to protocol, HPV negative women were referred to regular screening including a cytological exam every 3 years while HPV positive women were referred to colposcopy and closer follow-up. We evaluated the implementation of the protocol and the prediction of HPV testing as a triage tool for cervical intraepithelial lesions grade two or worse (CIN2+) in women with a cytological diagnosis of ASC-US.

Methods

During 2007-08 a total of 611 women from five reference laboratories in Catalonia with a novel diagnosis of ASC-US were referred for high risk HPV (hrHPV) triage using high risk Hybrid Capture version 2. Using routine record linkage data, women were followed for 3 years to evaluate hrHPV testing efficacy for predicting CIN2+ cases. Logistic regression analysis was used to estimate the odds ratio for CIN2 +.

Results

Among the 611 women diagnosed with ASC-US, 493 (80.7%) had at least one follow-up visit during the study period. hrHPV was detected in 48.3% of the women at study entry (mean age 35.2 years). hrHPV positivity decreased with increasing age from 72.6% among women younger than 25 years to 31.6% in women older than 54 years (p < 0.01).

At the end of the 3 years follow-up period, 37 women with a diagnosis of CIN2+ (18 CIN2, 16 CIN3, 2 cancers, and 1 with high squamous intraepithelial lesions -HSIL) were identified and all but one had a hrHPV positive test at study entry. Sensitivity to detect CIN2+ of hrHPV was 97.2% (95%confidence interval (CI) = 85.5-99.9) and specificity was 68.3% (95%CI = 63.1-73.2). The odds ratio for CIN2+ was 45.3 (95% CI: 6.2-333.0), when among ASC-US hrHPV positive women were compared to ASC-US hrHPV negative women.

Conclusions

Triage of ASC-US with hrHPV testing showed a high sensitivity for the detection of CIN2+ and a high negative predictive value after 3 years of follow-up. The results of this study are in line with the current guidelines for triage of women with ASC-US in the target age range of 25-65. Non adherence to guidelines will lead to unnecessary medical interventions. Further investigation is needed to improve specificity of ASC-US triage.

Keywords:
Human papillomavirus (HPV); Diagnosis of atypical squamous cell of undetermined significance (ASC-US); Triage; cervical cancer screening; hrHC2 testing