Downloaded from http://journals.lww.com/jlgtd by BhDMf5ePHKbH4TTImqenVHwt3+2Cz0wZsXsGn1zT+P2wk3on7NDCY1S1NwNxipq/ on 10/08/2020 Intraoperative Human Papillomavirus Test Predicts 24-Month High-Grade Squamous Intraepithelial Lesion Recurrence Saving Costs: A Prospective Cohort Study Jordi Rabasa, MD, PhD, 1 Ana Alcalde, MD, 1 Melissa Bradbury, MD, 1 José Luis Sánchez-Iglesias, MD, PhD, 1 Diana Guerrero, MD, 1 Cristina Forcada, MD, 1 Assumpció Pérez-Benavente, MD, PhD, 1 Silvia Cabrera, MD, PhD, 1 Santiago Ramón Y. Cajal, MD, PhD, 2,3 Javier Hernández, MD, PhD, 2,3 Ángel García, MD, PhD, 2 Cristina Centeno, MD, PhD, 1 and Antonio Gil-Moreno, MD, PhD 1,3 Objectives: The human papilloma virus (HPV) test is recommended in the posttreatment follow-up of cervical intraepithelial neoplasia. The aim of the study was to assess whether the intraoperative HPV (IOP-HPV) test had a similar diagnostic accuracy that HPV test performed at 6 months to predict high-grade squamous intraepithelial lesion (HSIL) recurrence. Materials and Methods: In a prospective cohort study, 304 women diagnosed with HSIL by biopsy and/or endocervical curettage before treatment and/or confirmation in the histological specimen were included. Immediately after surgery, HPV testing was performed. This test was com- pared with the test at 6 months and other predictors of recurrence. Patients were followed for 24 months. An economic analysis was performed to compare the costs of IOP-HPV and HPV test at 6 months. Results: Recurrence rate of HSIL was 6.2% (19 patients). The diagnostic accuracy of the IOP-HPV test to predict HSIL recurrence at 24 months was similar to the HPV test at 6 months, with comparative sensitivities of 100% versus 86.7%, specificities of 82.0% versus 77.9%, positive predictive values of 27.1% versus 18.1%, and negative predictive values of 100% ver- sus 99.0%. Direct economic saving per high-grade intraepithelial lesion patient was 172.8 €. Conclusions: The HPV test performed after loop electrosurgical resection procedure predicted recurrence of HSIL at 24 months with a similar diagnos- tic accuracy than the HPV test at 6 months. The use of the IOP-HPV test in the management of HSIL will allow early detection of the risk of recurrent disease and to save costs because of potential suppression of the need of HPV and follow-up controls at 6 months. Key Words: human papilloma virus, loop electrosurgical excision, intraepithelial lesion, costs, follow-up (J Low Genit Tract Dis 2020;24: 367–371) P ersistent high-risk human papilloma virus (HPV) infection is the causative agent of high-grade squamous intraepithelial lesion (HSIL) of the cervix and its precursor lesions. 1,2 It is estimated that approximately 54,000 women in Spain are annually diagnosed with cervical intraepithelial neoplasia (CIN) grade 2/3, the manage- ment of which represents a significant economic burden for the national health care system. 3 Women with HSIL are treated with loop electrosurgical resection procedure (LEEP) 4,5 and followed at regular intervals (usually 6 and 24 months) after LEEP, 6,7 in- cluding HPV testing in the follow-up controls. 8,9 It has been shown that the HPV test at 6 months has a higher sensitivity that cytology in detecting high-grade posttreatment disease has a sim- ilar specificity. 10 Intraoperative postconization HPV (IOP-HPV) testing has been proposed as an advantageous strategy for early identification patients with treatment failure (i.e., recurrent CIN 2–3 during follow-up), thereby facilitating the scheduling of an atten- uated follow-up for IOP-HPV–negative patients who are at very low risk of persistent disease. 11 In a previous prospective cohort study, we showed that IOP-HPV can accurately predict treatment HSIL recurrence after LEEP with similar diagnostic accuracy than conventional HPV test- ing at 6 months. 12 In this study, however, the length of follow-up was limited to 12 months. Therefore, the present study was con- ducted to replicate previous findings on the diagnostic accuracy of IOP-HPV at 24 months. Moreover, accurate prediction of HSIL recurrence at 24 months based on IOP-HPV testing may deem un- necessary to perform HPV testing at 6 months. Thus, direct cost savings according to tentative suppression of procedures included in the 6-month control assessment were estimated. METHODS Design This prospective cohort study of women diagnosed with HSIL/CIN 2–3 was carried out at the Unit of Gynecologic Oncol- ogy of Hospital Universitari Vall d‘Hebron, in Barcelona, Spain, between June 2015 and June 2019. The primary objective was to assess whether the IOP-HPV test had a similar diagnostic ac- curacy that the HPV test performed at 6 months after LEEP to predict treatment HSIL recurrence at 24 months. The secondary objective was to estimate direct cost savings based on suppression of the 6-month follow-up control, including office visit, cytology, and the HPV test. The study was approved by the institutional review board (date June 17, 2015, Registry Number PR(AMI) 29/2015). Written informed consent was obtained from all partic- ipants. No funding was received for this clinical study. Participants and Study Procedures We here included a cohort of 304 consecutive women diag- nosed with HSIL/CIN 2–3 by colposcopy-guided biopsy or endo- cervical curettage (ECC) during the 3 months before treatment and/or confirmation of HSIL/CIN 2–3 in the pathological study of the surgical specimen. Exclusion criteria were the presence of an immunosuppression disorder (acquired or congenital) and chronic treatment with immunosuppressant drugs. All patients 1 Gynecology Oncology Unit, Department of Gynecology and Obstetrics, Hos- pital Universitari Vall d‘Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain; 2 Department of Pathology, Hospital Universitari Vall d‘Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain; 3 Spanish Biomedical Research Net- work Centre in Oncology (CIBERONC), Madrid, Spain Reprint requests to: Jordi Rabasa, MD, Unit of Gynecologic Oncology, Department of Gynecology and Obstetrics, Hospital Universitari Vall d‘Hebron, Passeig Vall d‘Hebron 119-129, E-08035 Barcelona, Spain. E-mail: jordi2546@hotmail.com The authors have declared they have no conflicts of interest. This study was approved by ethics committee of Clinical Research of Hospital Universitari Vall d'Hebron on 17 June 2015 (Registry PR(AMI)29/2015). C.C. and A.G.-M. contributed equally to the study. J.R., A.A., M.B., J.L.S.I., S.C., A.P.-B., C.C., and A.G.M. participated in the conceptualization, methodology of the study, and writing of the article. J.R., D.G., and C.F. performed the data collection. S.R.Y.C., J.H., and A.G. participated in the methodology and data review. J.R., S.C., and C.C. performed the data analysis. All authors approved the final manuscript. © 2020, ASCCP DOI: 10.1097/LGT.0000000000000549 ORIGINAL RESEARCH ARTICLE:CERVIX AND HPV Journal of Lower Genital Tract Disease • Volume 24, Number 4, October 2020 367 Copyright © 2020 ASCCP. Unauthorized reproduction of this article is prohibited.