The Clinical Utility of HPV DNA, mRNA and p16INK4A/Ki-67 as Triage Tools for Low Grade Cervical Lesions LSIL and ASCUS
Christine White, Loretto Pilkington, Helen Keegan, Sharon O'Toole, Cathy Spillane, Linda Sharp, Ruth O'Kelly, Grainne Flannelly, John J O'Leary, Cara M Martin. Trinity College Dublin, Dublin, Ireland; Coombe Women and Infants University Hospital, Dublin, Ireland; National Cancer Registry, Cork, Ireland; National Maternity Hospital, Dublin, Ireland
Background: There remains considerable challenges over the management of low grade abnormalities, due to the high prevalence of transient HPV infections in low-grade disease HPV DNA triage is limited. The use of HPV E6/E7 mRNA detection and biomarkers such as p16INK4A and Ki-67 has potential to identify clinically significant infections improving diagnostic specificity. The aim of this study is to investigate the utility of these markers for detecting women at risk of developing high grade disease presenting at colposcopy with LSIL/ASCUS.
Design: Cervical smears for HPV testing and immunocytochemical analysis were collected from 1079 women presenting with LSIL/ASCUS at their first visit to colposcopy at the National Maternity Hospital, Dublin. HPV DNA was detected by Hybrid Capture II (Qiagen, UK), HPV E6/E7 mRNA expression by the PreTect™ HPV Proofer (NorChip AS, Norway) and p16INK4A/Ki-67 expression was assessed using CINtec PLUS (Roche).
Results: HPV DNA and mRNA testing has been performed on 1079 patient samples, a subset of 430 cases have been tested for p16INK4A/Ki-67 dual expression. Over all HPV DNA testing provided the highest sensitivity, 93% (95% CI 0.9156-0.9455), for detection of CIN 2+. However, HPV mRNA and p16INK4A/Ki-67 co-expression provided enhanced specificity 70% (95% CI 0.7277-0.8495) and 84% (95% CI 0.8232-0.859). Analysis is currently underway to investigate combined HPV and immunocytochemical testing for optimal clinical sensitivity and specificity.
Conclusions: This offers prospective evidence that HPV testing in the management of women presenting with low grade abnormalities could be useful in detecting those at risk of developing high grade disease. This study is carried out under CERVIVA the Irish Cervical Screening Research Consortium funded by the Health Research Board and is supported by The Irish Cancer Society.
Tuesday, March 5, 2013 9:15 AM
Proffered Papers: Section F, Tuesday Morning