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

Abstract

BackgroundA 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.MethodsDuring 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 +.ResultsAmong 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.ConclusionsTriage 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.

Low Prevalence of Cervical Cancer Screening Among HIV-Positive Women in Catalonia (Spain)

“…In conclusion, the low frequency and coverage of cervical screening found in this study is consistent with the high prevalence of infection with oncogenic HPV types, cervical lesions, and cervical cancer in HIVpositive women in Catalonia. As indicated by other studies, screening in HIV-positive women and general population should be complemented with diagnostic techniques that allow for detection of asymptomatic HPV infections and predict cervical intraepithelial neoplasia [15,16], as well as the HPV vaccine as a primary prevention measure when its safety and immunogenicity is demonstrated in HIV-positive women.…”

Cervical cancer screening cotesting with cytology and MRNA HPV E6/E7 yields high rates of CIN2+ lesions in young women

“…The current cervical cancer screening program follows an opportunistic model with cytological testing every 3–5 years starting at ages 25 or 30 and ending at 65 . Reflex hrHPV is performed in cases with ASC‐ US borderline cytology . The current study intended to assess the feasibility of primary HPV screening in Madrid.…”

Screening of cervical cancer in Catalonia 2006–2012

“…The laboratories included were Hospital Universitario Dr. Josep Trueta, Consorcio hospitalario de Vic, Hospital Universitario Joan XXIII, Hospital del Mar, Hospital universitario de Bellvitge, Hospital de Granollers, Hospital de Althaia, and Laboratorio de Atención Primaria Dr. Robert. The main outcome was histological confirmation of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) [ 10 , 11 ]. The risk of CIN2+ was evaluated following a Kaplan–Meier approaches.…”

“…We evaluated the triage of ASC-US using HPV test for the prediction of CIN2+ in 611 women with a mean age of 34.5 years (range 15–79 years) [ 11 ]. Among these women, we obtained an adequate follow-up for 493 (80.7%) women, of which 48.3% were positive for HPV.…”

“…Only one case (0.4%) was diagnosed with CIN2. The sensitivity of the HPV test to detect CIN2+ was 97.2% (95% CI: 85.5–99.9) with a specificity of 68.3% (CI: 63.1–73.2) [ 11 ].…”