Recurrent high-grade cervical lesion after primary conization is associated with persistent human papillomavirus infection in Norway

• Published in: Gynecologic oncology 2014-05, Vol.133 (2), p.159-166
• Main Authors: Vintermyr, O.K, Iversen, O, Thoresen, S, Quint, W, Molijn, A, de Souza, S, Rosillon, D, Holl, K
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alphapapillomavirus - genetics; Cervical intraepithelial neoplasia; Cervical Intraepithelial Neoplasia - pathology; Cervical Intraepithelial Neoplasia - virology; Conization; DNA, Viral - analysis; Female; Hematology, Oncology and Palliative Medicine; High-risk HPV; Human papillomavirus; Human papillomavirus 16 - genetics; Human papillomavirus 18 - genetics; Humans; Middle Aged; Neoplasm Recurrence, Local - pathology; Neoplasm Recurrence, Local - virology; Norway; Obstetrics and Gynecology; Papillomavirus Infections - virology; Recurrence; Registries; Retrospective Studies; Sequence Analysis, DNA; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - surgery; Uterine Cervical Neoplasms - virology
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2014.03.004

Abstract Objective This retrospective registry-based study aimed to assess the human papillomavirus (HPV)-type distribution in primary and recurrent high-grade cervical intraepithelial neoplasia (CIN2 +), and to discriminate pre-existing from newly-acquired infections. Methods Cervical specimens from 58 women (median age (Q1–Q3): 37.6 (31.7–44.9)) who underwent primary (1998–2003) and repeat conizations were confirmed as CIN2 + during expert pathology review. HPV testing was performed using PCR MP-TS123 Luminex for 16 HPV types. Molecular HPV16 E6 and HPV18 LCR DNA sequencing was performed on specimens with persistent HPV16/18. Results All 58 paired cones were HPV positive; 49 had CIN3 + in the primary cone. Forty-seven (95.9%) women with primary CIN3 + and recurrent CIN2 + had persistent high-risk ( hr ) HPV infection, of which 74.5% were HPV16/18. Two women had probable newly-acquired HPV16/52/56 and HPV39 infections. One woman with persistent HPV52 also had a probable new HPV16 E6 variant in the recurrent CIN2 +. Median time delay (Q1–Q3) between conizations was 2.0 years (1.1–4.0), being shorter for women older than 40 years: 2.6 years (1.1–3.7) than for women younger than 40 years: 6.0 years (2.0–8.7). Primary conization histology revealed CIN3, cervical adenocarcinoma in situ and microinvasive carcinomas in 43 (87.8%), 5 (10.2%) and 1 (2.0%) women, respectively. Primary HPV16- and HPV18-infected CIN3 + had a shorter delay between conizations: 1.8 years (1.2–4.4) and 2.2 years (0.4–NE), respectively, compared to HPV33-: 3.8 years (3.3–7.8) or other HPV type-infected: 8.2 years (6.0–NE) CIN3 +. Conclusions Routine post-conization hr- HPV DNA testing together with cervical cytology may provide a better prediction for potential recurrent disease. Further, primary prevention through adolescent vaccination may prevent CIN2 + and its recurrence.