Outcomes of High-Grade Cervical Dysplasia with Positive Margins and HPV Persistence after Cervical Conization

Author:

Giannini Andrea1ORCID,Di Donato Violante1ORCID,Sopracordevole Francesco2,Ciavattini Andrea3,Ghelardi Alessandro4,Vizza Enrico5,D’Oria Ottavia6ORCID,Simoncini Tommaso7ORCID,Plotti Francesco8,Casarin Jvan9,Golia D’Augè Tullio1ORCID,Cuccu Ilaria1,Serati Maurizio9,Pinelli Ciro10,Bergamini Alice11,Gardella Barbara12ORCID,Dell’Acqua Andrea13,Monti Ermelinda13,Vercellini Paolo13,D’Ippolito Giovanni14ORCID,Aguzzoli Lorenzo14,Dario Mandato Vincenzo14ORCID,Giannella Luca3ORCID,Scaffa Cono15ORCID,Ditto Antonino16,Falcone Francesca15ORCID,Borghi Chiara17,Malzoni Mario18,Di Giovanni Alessandra18,Salerno Maria Giovanna6,Liberale Viola19,Contino Biagio19,Donfrancesco Cristina20,Desiato Michele20,Perrone Anna Myriam21ORCID,De Iaco Pierandrea21,Ferrero Simone2223ORCID,Sarpietro Giuseppe24ORCID,Matarazzo Maria G.24,Cianci Antonio24,Cianci Stefano25,Bosio Sara26,Ruisi Simona26,Mosca Lavinia27,Tinelli Raffaele28ORCID,De Vincenzo Rosa29ORCID,Zannoni Gian Franco29,Ferrandina Gabriella29,Petrillo Marco30ORCID,Capobianco Giampiero30ORCID,Carlea Annunziata31ORCID,Zullo Fulvio31,Muschiato Barbara32,Palomba Stefano33ORCID,Greggi Stefano15,Spinillo Arsenio12,Ghezzi Fabio910,Colacurci Nicola27,Angioli Roberto8,Benedetti Panici Pierluigi1,Muzii Ludovico1ORCID,Scambia Giovanni29,Raspagliesi Francesco16,Bogani Giorgio16ORCID

Affiliation:

1. Department of Gynecological, Obstetrical and Urological Sciences, “Sapienza” University of Rome, 00161 Rome, Italy

2. Gynecological Oncology Unit, Centro di Riferimento Oncologico-National Cancer Institute, 33081 Aviano, Italy

3. Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, 60126 Ancona, Italy

4. Azienda Usl Toscana Nord-Ovest, UOC Ostetricia e Ginecologia, Ospedale Apuane, 54100 Massa, Italy

5. Gynecologic Oncology Unit, Department of Experimental Clinical Oncology, IRCCS “Regina Elena” National Cancer Institute, 00144 Rome, Italy

6. Department of Woman’s and Child’s Health, Obstetrics and Gynecological Unit, San Camillo-Forlanini Hospital, 00152 Rome, Italy

7. Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy

8. Department of Obstetrics and Gynecology, Campus Bio-Medico University of Rome, 00128 Rome, Italy

9. Department of Obstetrics and Gynecology, ‘Filippo Del Ponte’ Hospital, University of Insubria, 21100 Varese, Italy

10. Ospedale di Circolo Fondazione Macchi, 21100 Varese, Italy

11. Department of Obstetrics and Gynecology, IRCCS Ospedale San Raffaele, 20100 Milano, Italy

12. IRCCS S. Matteo Foundation, Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, 27100 Pavia, Italy

13. Gynaecology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy

14. Division of Obstetrics and Gynecology, Cesare Magati Hospital, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42019 Scandiano, Italy

15. Gynecology Oncology Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy

16. Gynecological Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy

17. Department of Obstetrics and Gynecology, S. Anna University Hospital, 44121 Ferrara, Italy

18. Endoscopica Malzoni, Center for Advanced Endoscopic Gynecological Surgery, 83100 Avellino, Italy

19. Department of Obstetrics and Gynecology, Ospedale Maria Vittoria, 10144 Torino, Italy

20. Department of Obstetrics and Gynecology, Azienda ASL Frosinone, Ospedale S Trinità di Sora, 03039 Sora, Italy

21. Gynecologic Oncology Unit, Sant’Orsola-Malpighi Hospital, 40138 Bologna, Italy

22. Academic Unit of Obstetrics and Gynaecology, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy

23. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genova, 16132 Genova, Italy

24. Department of General Surgery and Medical Surgical Specialties, Gynecological Clinic University of Catania, Via S. Sofia 78, 95124 Catania, Italy

25. Department of Gynecologic Oncology, Università degli Studi di Messina, Policlinico G. Martino, 98122 Messina, Italy

26. San Paolo Hospital, Università degli Studi di Milano, 20142 Milan, Italy

27. Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy

28. Department of Obstetrics and Gynecology, “Valle d’Itria” Hospital, Martina Franca, Via San Francesco da Paola, 74015 Taranto, Italy

29. UOC Ginecologia Oncologica, Dipartimento per la Salute Della Donna e del Bambino e Della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, 00168 Rome, Italy

30. Gynecologic and Obstetric Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy

31. Department of Neuroscience, Reproductive Science and Dentistry, School of Medicine, University of Naples Federico II, 80131 Naples, Italy

32. Studio Medico Muschiato, Loano & Finale Ligure, 17025 Loano, Italy

33. Unit of Obstetrics and Gynecology, GOM of Reggio Calabria & University ‘Magna Graecia’ of Catanzaro, 88100 Catanzaro, Italy

Abstract

The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 (HR: 4.88 (95%CI: 1.10, 12.41); p = 0.035) and positive endocervical instead of ectocervical margins (HR: 6.44 (95%CI: 2.80, 9.65); p < 0.001) were associated with increased risk of persistence/recurrence. Via multivariate analyses, only positive endocervical instead of ectocervical margins (HR: 4.56 (95%CI: 1.23, 7.95); p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence.

Publisher

MDPI AG

Subject

Pharmacology (medical),Infectious Diseases,Drug Discovery,Pharmacology,Immunology

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