Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2

Rikke Kamp Damgaard; David Jenkins; Mark H Stoler; Maurits de Koning; Miekel van de Sandt; Kathrine Dyhr Lycke; Johnny Kahlert; Patti E Gravitt; Wim G V Quint; Torben Steiniche; Lone Kjeld Petersen; Anne Hammer

doi:10.1016/j.ajog.2024.01.029

Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2

Am J Obstet Gynecol. 2024 Feb 7:S0002-9378(24)00072-3. doi: 10.1016/j.ajog.2024.01.029. Online ahead of print.

Affiliations

¹ Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark; Department of Obstetrics and Gynecology, Gødstrup Hospital, Herning, Denmark; NIDO, Center for Research and Education, Gødstrup Hospital, Herning, Denmark.
² Viroclinics-DDL, Cerba Research, Rijswijk, the Netherlands.
³ Department of Pathology, University of Virginia, Charlottesville, VA.
⁴ Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
⁵ National Cancer Institute, Bethesda, MD.
⁶ Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark; Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
⁷ Department of Gynaecology and Obstetrics, Odense University Hospital, Odense, Denmark.
⁸ Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark; Department of Obstetrics and Gynecology, Gødstrup Hospital, Herning, Denmark; NIDO, Center for Research and Education, Gødstrup Hospital, Herning, Denmark. Electronic address: ahlauridsen@clin.au.dk.

PMID: 38336125
DOI: 10.1016/j.ajog.2024.01.029

Abstract

Background: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression.

Objective: This study aimed to describe human papillomavirus HPV type-specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2.

Study design: We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF₁₀-DEIA-LiPA₂₅ system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model.

Results: A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37-1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03-1.61), whereas no differences were observed across age groups.

Conclusion: The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women.

Keywords: cervical cancer prevention; cervical intraepithelial neoplasia grade 2; clinical management; human papillomavirus genotyping; risk assessment.