OC 10-06PERFORMANCE OF HPV-E7 ONCOPROTEIN DETECTION AS A TRIAGE METHOD TO COLPOSCOPY FOR HPV 16/18 POSITIVE WOMEN, COMPARED TO NO TRIAGE, OR FOR HIGH-RISK HPV (NON16/18) 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

High-risk (hr) HPV detection with HPV16/18 genotyping is considered a better method of primary cervical screening than cytology^1-4, which tends to become a triage test for hr (non16/18) HPV positive women to colposcopy⁵. The objective of the presented study is to assess the performance of the detection of E7HPV protein as a triage method for women positive for either hrHPV (non16/18) or HPV16/18.

Methods

Between February 2013 and April 2014, 1,258 women aged 30-60 years (mean: 43.7), were recruited, at the Family Planning Centre, Hippokratio Hospital, Thessaloniki, Greece, and at the Department of Gynecology, Charité Campus Benjamin Franklin and Campus Mitte, Berlin, Germany, and provided a cervicovaginal sample, according to the “PIPAVIR” study protocol, which aimed to assess the diagnostic accuracy of HPV DNA test, cytology and E7 test for cervical screening. Cytological evaluation was performed using Liquid Based Cytology (ThinPrep® Hologic, Bedford, MA, USA). An aliquot of each sample was used for hrHPV and E7 detection using HPV Multiplex Genotyping (MPG) and a hrHPV E7 Sandwich ELISA method, developed during the project, respectively. Different hrE7 ELISA formats were used detecting HPV 16/18/31/33/35/39/45/51/52/56/58/59 (recomWell HPV HR screen); HPV16/31/33/35/52/58 (recomWell HPV plus); or HPV16/18/45 (recomWell HPV 16/18/45). Women positive for cytology [atypical squamous cells of undetermined significance or worse (ASCUS+)], hrHPV DNA or E7 were referred for colposcopy. Biopsies and histological assessment of the samples were performed in cases of abnormal colposcopic impression.

Results

Among 1,254 valid tests, hrHPV and HPV16/18 prevalence was 21.7% and 14.7% respectively. Cytology report was ASCUS+ in 7.1%. Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+) was detected in 25 women (2.0%). For HPV 16/18 positive women with no triage, sensitivity, positive predictive value (PPV) and the number of colposcopies needed to detect one case of CIN2+ were 100.0%, 8.7% and 11.5 respectively. The respective values for E7 testing as a triage method to colposcopy for these women were 100.0%, 15.2% and 6.6. Sensitivity and PPV for the triage of women positive for hrHPV (non 16/18) were 55.5% and 29.4% for cytology; for E7 test the respective values were 77.7% and 24.1%.

Conclusion

Triage, of HPV 16/18 positive women, to colposcopy with the E7 test presents better performance than no triage, decreasing the number of colposcopies needed to detect one CIN2+. In addition, triage of hr (non16/18) HPV positive women with E7 test presents better sensitivity and slightly worse PPV than cytology.

References

[1] N.W. Bulkmans, L. Rozendaal, P.J. Snijders, F.J. Voorhorst, A.J. Boeke, G.R. Zandwijken, 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 May 20;110(1):94-101.

[2] P.E. Castle, M.H. Stoler, T.C. Wright, Jr., A. Sharma, T.L. Wright, C.M. Behrens. 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. The Lancet Oncology 2011 Sep;12(9):880-90.

[3] T. Agorastos, K. Chatzistamatiou, T. Katsamagkas, G. Koliopoulos, A. Daponte, T. Constantinidis, et al. 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;10(3):e0119755.

[4] G. Ronco, J. Dillner, K.M. Elfstrom, S. Tunesi, P.J. Snijders, M. Arbyn, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 2014 Feb 8;383(9916):524-32.

[5] W.K. Huh, K.A. Ault, D. Chelmow, D.D. Davey, R.A. Goulart, F.A. Garcia, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Obstetrics and gynecology 2015 Feb;125(2):330-7.