OC 08-02PERFORMANCE OF HIGH-RISK HPV DNA GENOTYPING FOR PRIMARY CERVICAL CANCER SCREENING AND TRIAGE OF HPV-POSITIVE WOMEN, COMPARED TO CYTOLOGY. RESULTS OF THE PIPAVIR STUDY

08. Screening methods
K. Chatzistamatiou 1, T. Agorastos 1, T. Moysiadis 2, E. Angelis 3, I. Lekka 4, A. Kaufmann 5, E. Boschetti-Grützmacher 5, A. Krings 5, I. Hagemann 6, I. Koch 7, O. Boecher 7, E. Soutschek 7, A. Skenderi 8, S. Angelidou 9, E. Katsiki 9, N. Maglaveras 4, A. Schneider 5, P. Jansen-Duerr 10.
14th Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Hippokratio General Hospital, Thessaloniki (Greece), 2Institute of Applied Biosciences, Centre for Research & Technology - Hellas, 57001 Thessaloniki (Greece), 3School of Informatics, Faculty of Sciences, Aristotle University of Thessaloniki, Thessaloniki (Greece), 4Laboratory of Bioinformatics, Department of Medicine, Aristotle University of Thessaloniki, Thessaloniki (Greece), 5Department of Gynecology, Charité Campus Benjamin Franklin and Campus Mitte, Berlin (Germany), 6MVZ Im Mare. Kiel (Germany), 7Mikrogen GmbH, Neuried (Germany), 8Laboratory of Cytology, Hippokratio General Hospital, Thessaloniki (Greece), 9Department of Histopathology, Hippokratio General Hospital, Thessaloniki (Greece), 10Research Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck (Austria)

Background / Objectives

As high-risk (HR) HPV types are detected in 99.7% of cervical cancer cases and in most of pre-invasive cases, HPV detection may be an alternative as a screening test for the detection of precancerous cervical lesions1. In fact, HR-HPV detection is increasingly considered a better method of primary screening than cytology2-5. The objective of the presented study is to assess the performance of (HR) HPV DNA genotyping as a method of primary cervical cancer screening and triage of HPV positive women to colposcopy compared to liquid-based cytology (LBC) in an urban population of Greek women.


Methods

Between February 2013 and April 2014, 1,519 women aged 30-60 years (mean: 43,8), who attended routine cervical cancer screening at the Family Planning Centre, Hippokratio Hospital of Thessaloniki, Greece, provided a cervicovaginal sample for the study. The women were recruited according to the protocol of the PIPAVIR study, which aimed to assess the diagnostic accuracy of HPV DNA testing, cytology and E7-protein testing for cervical cancer screening. The substudy presented herein investigates the first two kinds of testing. Cytological evaluation was performed using LBC (ThinPrep® Hologic, Bedford, MA, USA). An aliquot of each sample was used in order to detect HR HPV using HPV Multiplex Genotyping (MPG), a PCR-based technique. Women positive for cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] or HR HPV were referred for colposcopy. Colposcopically-guided biopsies followed by histological assessment of the samples were performed in cases of abnormal colposcopic impression.


Results

Among 1,432 valid tests the prevalence of HR-HPV and HPV 16 and/or 18 was 18.8% and 11.7% respectively. The cytological report was ASCUS or worse in 6.8% of the women tested. Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+) was detected in 21 women (1.5%). Sensitivity of cytology (ASCUS or worse) and HPV DNA testing for the detection of CIN2+ was 52.4% and 100%, and specificity was 93.8% and 82.3% respectively. The Positive and Negative Predictive Value (PPV and NPV) were 11.2% and 99.2% for cytology and 7.8% and 100% for HPV testing respectively. HPV 16/18 genotyping presented better sensitivity than cytology concerning triage of HPV positive women to colposcopy (61.9% vs 52.4% respectively), but worse PPV (7.7% vs 11.2% respectively).


Conclusion

For women older than 30 years, HR HPV full genotyping could represent an alternative methodology for primary cervical screening as well as for triage of HPV positive women to colposcopy, in comparison to HR HPV DNA primary screening combined with cytological triage of HPV positive women.


References

1.Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. The Journal of pathology. 1999; 189:12–19. PMID: 10451482
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. PMID: 15054873
3.Castle PE, Stoler MH, Wright TC Jr, Sharma A, Wright TL, Behrens CM. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study. Lancet Oncol. 2011; 12: 880–890. doi: 10.1016/S1470-2045(11)70188-7 PMID: 21865084
4.Agorastos T, Chatzistamatiou K, Katsamagkas T, Koliopoulos G, Daponte A, Constantinidis T, Constantinidis TC; HERMES study group. Primary screening for cervical cancer based on high-risk human papillomavirus (HPV) detection and HPV 16 and HPV 18 genotyping, in comparison to cytology.PLoS One. 2015 Mar 20;10(3):e0119755. doi: 10.1371/journal.pone.0119755. eCollection 2015.

5.Ronco G, Dillner J, Elfstrom KM, Tunesi S, Snijders PJ, Arbyn M, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials.Lancet. 2014; 383: 524–532. doi: 10.1016/S0140-6736(13)62218-7 PMID: 24192252