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

BACKGROUND: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 (CIN2) since regression rates are high and because 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: Here, we aimed to describe HPV type-specific persistence/progression in women undergoing active surveillance for CIN2.

STUDY DESIGN: We conducted a historical cohort study on women aged 23-40 years diagnosed with CIN2 at Aarhus University Hospital, 2000-2010. 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 two years after index diagnosis and no LEEP prior to this. Archived tissue samples underwent HPV genotyping using the HPV SPF10 -DEIA-LiPA25 system (DNA ELISA kit HPV SPF10 and RHA Kit HPV SPF10-LiPA25). Persistence/progression were defined as having a record of ≥CIN2 in the DPDB determined on the last and worst diagnosis on a biopsy or Loop Electrosurgical Excision Procedure (LEEP) specimen during follow-up. We estimated the relative risk (RR (95% CI)) of persistence/progression using a modified Poisson model.

RESULTS: A total of 455 women were included. Two-thirds were ≤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 ≥CIN2 during follow-up; 70.5% in HPV16 positive and 29.5% in those positive for other HPV types. HPV16 was associated with a significantly higher risk of persistence/progression (RR 1.64 (95% CI (1.37-1.95)) compared to non-HPV16. The risk persistence or progression was highest in HPV16-positive women with a high-grade index cytology compared to HPV16-positive women with a low-grade cytology (RR 1.29 (95% CI (1.03-1.61-)), whereas no differences were observed across age groups.

CONCLUSION: Highest risk of persistence/progression was observed among HPV16-positive women, particularly in those with an associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women.