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. 2023 Sep;102(9):1227-1235.
doi: 10.1111/aogs.14627. Epub 2023 Jul 19.

High prevalence of HPV16 and high-grade cytology in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2

Rikke Kamp Damgaard  1   2   3 , David Jenkins  4 , Mark H Stoler  5 , Miekel M van de Sandt  4 , Kathrine Dyhr Lycke  1   2   3 , Maurits N C de Koning  4 , Wim G V Quint  4   6 , Torben Steiniche  1   7 , Lone Kjeld Petersen  8   9 , Anne Hammer  1   2   3
Affiliations

High prevalence of HPV16 and high-grade cytology in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2

Rikke Kamp Damgaard et al. Acta Obstet Gynecol Scand. 2023 Sep.

Abstract

Introduction: Many countries have adopted active surveillance in women with cervical intraepithelial neoplasia grade 2 (CIN2), leaving the lesion untreated. However, there is a lack of consensus on the eligibility criteria for active surveillance across countries, with some abstaining from active surveillance in women with human papilloma virus 16 (HPV16) or a high-grade cytology. Here, we aimed to describe the distribution of HPV genotypes, age, and cytology in women undergoing active surveillance for CIN2.

Material and methods: We conducted a single-center cross-sectional study on women aged 23-40 undergoing active surveillance for CIN2 during 2000-2010. Women were identified through the Danish Pathology Data Bank (DPDB) at Aarhus University Hospital, Denmark. We collected information on basic characteristics and results of histopathological examinations via DPDB. Women were deemed eligible for inclusion if they had a subsequent biopsy after index CIN2, and had no prior record of CIN2+, hysterectomy, or cone biopsy. Archived biopsies underwent HPV genotyping using the HPV SPF10 - DEIA-LiPA25 system, and the diagnosis was re-evaluated by three expert pathologists. We used the Chi squared-test (p-value) for comparison across groups.

Results: We identified 3623 women with CIN2 of whom 455 (12.6%) were included. Most women were 30 years or younger (73.8%), and half (48.8%) had a high-grade index cytology. The prevalence of any high-risk HPV was 87.0%, with HPV16 being the most prevalent genotype (35.6%). The prevalence of HPV16 was significantly higher in women aged 30 or younger (39.3%) compared to women older than 30 years (25.2%) (p = 0.006). Upon expert review, 261 (57.4%) had CIN2 confirmed, whereas 56 (12.3%) were upgraded to CIN3 and 121 (26.6%) were downgraded to CIN1/normal. While the HPV16 prevalence was similar between community and expert confirmed CIN2, the prevalence of HPV16 was significantly higher in women with expert CIN3 compared to women with expert CIN1/normal (64.3% vs. 19.0%, p = 0.001).

Conclusions: The high prevalence of HPV16 and high-grade cytology imply that these women may be perceived as a high-risk population and non-eligible for active surveillance in countries outside Denmark. Future studies should investigate the importance of HPV, age, cytology, and expert review on risk of progression to help refine criteria for active surveillance.

Keywords: HPV genotype; active surveillance; cervical cancer prevention; cervical cancer screening; cervical intraepithelial neoplasia grade 2 (CIN2); cytology.

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Conflict of interest statement

AH and RD have received reagents at reduced cost from Roche Denmark. DJ has received a consultant fee and loan of a computer from DDL Diagnostic Laboratory. MHS has received consultant fees from Roche, Merck, BD Life Science, Abbott Molecular, Inovio Pharmaceuticals and speaker's fee from Roche and BD Life Science without any relation to the work of this study. KL has received a speaker's fee from AstraZeneca Denmark and LKP for MSD Denmark. MdK has consulting fees from Viroclinics‐DDL outside and an indirect minory shareholding with no voting rights in Cerba Healthcare outside the work of this study. The remaining authors declare no conflicts of interest.

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