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

O K Vintermyr; O Iversen; S Thoresen; W Quint; A Molijn; S de Souza; D Rosillon; K Holl

doi:10.1016/j.ygyno.2014.03.004

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

Gynecol Oncol. 2014 May;133(2):159-66. doi: 10.1016/j.ygyno.2014.03.004. Epub 2014 Mar 11.

Authors

O K Vintermyr¹, O Iversen², S Thoresen³, W Quint⁴, A Molijn⁴, S de Souza⁵, D Rosillon⁶, K Holl⁶

Affiliations

¹ Department of Pathology, Haukeland University Hospital, Norway; The Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway. Electronic address: olav.vintermyr@helse-bergen.no.
² Institute of Clinical Medicine, University of Bergen, Bergen, Norway; Women's Clinic, Haukeland University Hospital, Bergen, Norway.
³ Abbvie AS, Norway.
⁴ DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
⁵ 4Clinics, Paris, France.
⁶ GlaxoSmithKline Vaccines, Wavre, Belgium.

PMID: 24631451
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: 1.8years (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.

Trial registration: ClinicalTrials.gov NCT00924794.

Keywords: Cervical intraepithelial neoplasia; Conization; High-risk HPV; Human papillomavirus; Recurrence.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Alphapapillomavirus / genetics*
Conization
DNA, Viral / analysis*
Female
Human papillomavirus 16 / genetics
Human papillomavirus 18 / genetics
Humans
Middle Aged
Neoplasm Recurrence, Local / pathology
Neoplasm Recurrence, Local / virology*
Norway
Papillomavirus Infections / virology*
Registries
Retrospective Studies
Sequence Analysis, DNA
Uterine Cervical Dysplasia / pathology
Uterine Cervical Dysplasia / virology*
Uterine Cervical Neoplasms / pathology
Uterine Cervical Neoplasms / surgery
Uterine Cervical Neoplasms / virology*

Substances

DNA, Viral

Associated data

ClinicalTrials.gov/NCT00924794