HPV-16 identified as highest risk for CIN2 progression in women under active surveillance

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A recent study found that women with human papillomavirus -16 undergoing surveillance for cervical intraepithelial neoplasia grade 2 are at the highest risk of progression to more severe cervical lesions.

HPV-16 identified as highest risk for CIN2 progression in women under active surveillance | Image Credit: © rh2010 - © rh2010 - stock.adobe.com.

HPV-16 identified as highest risk for CIN2 progression in women under active surveillance | Image Credit: © rh2010 - © rh2010 - stock.adobe.com.

Among women undergoing surveillance for cervical intraepithelial neoplasia grade 2 (CIN2), those with human papillomavirus (HPV)-16 are at the highest risk of progression to cervical intraepithelial neoplasia grade ≥3 (≥CIN3), according to a recent study published in the American Journal of Obstetrics & Gynecology.1

Takeaways

  1. HPV-16 is the most prevalent and carries the highest risk of CIN2 progression, with a 70.5% chance of persistence or progression.
  2. Active surveillance for CIN2 shows histologically verified progression in 15.1% of patients within 6 months and 33.3% within 24 months.
  3. Women under active surveillance undergo colposcopy, smear, and cervical biopsies every 4 to 6 months for up to 2 years.
  4. The study included 455 women aged 23 to 40 years diagnosed with CIN2, tracked through the Danish Pathology Data Bank from 2000 to 2010.
  5. HPV genotyping and related cytology are recommended for better clinical management of women diagnosed with CIN2 to identify those at higher risk of disease progression.

Active surveillance is often used in women with CIN2 to reduce rates of loop electrosurgical excision procedure (LEEP). However, this method may increase discomfort because of repeated colposcopic examinations, making it vital to determine objective biomarkers of CIN2 progression.

Efficacy has been reported from active surveillance of CIN2, with one study finding histologically verified progression in 15.1% of patients receiving surveillance within 6 months and 33.3% within 24 months.2 Only 0.3% of participants had cervical cancer by 24 months, none of which were worse than stage 2.

HPV genotyping may be a biomarker of progression to ≥CIN3, as data has indicated variations in risk based on genotype.1 While one study found an increased risk of progression from HPV-16, the evaluation was limited by a small sample size.

Investigators conducted a study assessing HPV genotype-specific risk of progression among women receiving active surveillance for CIN2 using nationwide registries in Denmark. Cytology-based screening for cervical cancer has been recommended in Denmark since 1986, and cytology-based screening has been offered since 2007.1

Repeated cytology testing is recommended in women with cervical intraepithelial neoplasia grade 1, and those with abnormal screening results may receive repeat testing or colposcopy-directed biopsies. Active surveillance includes colposcopy, smear, and cervical biopsies every 4 to 6 months for up to 2 years.

Women diagnosed with CIN2 at the Department of Pathology, Aarhus University Hospital and receiving active surveillance between January 1, 2000, and December 31, 2010, were included in the analysis. Participants were selected from the Danish Pathology Data Bank (DPDB).

Women aged 23 to 40 years when diagnosed and with a cervical biopsy recorded in the first follow-up were eligible for study inclusion. Exclusion criteria included prior ≥CIN2 record, LEEP, or hysterectomy in the DPDB.

The index cytology was the most recent cervical cytology sample in the DPDB within 6 months of CIN2 diagnosis and included low-grade index cytology or lower and high-grade index cytology. HPV testing was reviewed by an expert panel of 3 pathologists with over 20 years of gynecologic pathology experience.1

Persistence and progression were reported together as a single primary outcome, determined by a subsequent ≥CIN2 record in the DPDB during the surveillance period. The reported outcome was based on the worst diagnosis from a cervical biopsy or a LEEP specimen.

There were 455 women included in the final analysis, aged a median 27.1 years. A high-grade index cytology record was identified in 48.8%, CIN2 during follow-up in 16%, ≥CIN3 in 36.4%, and cervical cancer in 0.7%. A median 2 follow-up visits were reported, with a median follow-up period of 16 months for women with regression and 11 months for those with persistence or progression.1

Any high-risk HPV (hrHPV) was reported in 87% of women, with a single hrHPV genotype found in 49.5% and multiple hrHPV genotypes in 39.5%. HPV-16 was the most prevalent genotype in 35.6%, followed by HPV-51 in 15.1%, HPV-31 in 14.7%, HPV-52 in 14.5%, HPV-18 in 11.4%, and HPV-33 in 8.1%.

Persistence or progression risks varied between HPV genotypes, with the highest of 70.5% reported for HPV-16. In comparison, rates were 48.8% for HPV-18 and 16.7% for HPV-59.1

The relative risk of persistence or progression in women with HPV-16 was 1.64, indicating a significant increase. No difference in persistence or progression risk was observed from single infections vs multiple infections.

These results indicated an increased risk of persistence or progression of CIN2 among women with HPV-16. Investigators concluded HPV genotyping and related cytology may be useful for clinically managing women diagnosed with CIN2.1

References

  1. Damgaard RK, Jenkins D, Stoler MH, et al. 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;230:655.e1-10. doi:10.1016/j.ajog.2024.01.029
  2. Krewson C. Evaluating efficacy of active surveillance for CIN2. Contemporary OB/GYN. December 13, 2023. Accessed June 24, 2024. https://www.contemporaryobgyn.net/view/evaluating-efficacy-of-active-surveillance-for-cin2
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