Risk of cervical intraepithelial neoplasia grade 2 or worse in women aged ≥ 69 referred to colposcopy due to an HPV-positive screening test

Abstract

Background: Cervical cancer incidence and mortality rates are high in older women in many developed countries, including Denmark. Therefore, Danish women aged 69 and older were invited for one additional human papilloma virus (HPV) based screening test in 2017. Here, we describe the clinical management and detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) in screen-positive women referred for colposcopy.

Methods: We conducted an observational study in public gynecology departments in Central Denmark Region, Denmark. Women were eligible for enrolment if they were aged 69 + in 2017, HPV positive on a screening test taken between April 20^th, 2017, and December 31^st, 2017, and had been referred for direct colposcopy. Data on participants' characteristics, colposcopic findings, and histological outcomes were collected from medical records and the Danish Pathology Databank. We estimated the proportion of women with CIN2 + at the first colposcopy visit and at end of follow up including 95% confidence intervals (CIs).

Results: A total of 191 women were included with a median age of 74 years (IQR: 71-78). Most women (74.9%) did not have a fully visible transformation zone at colposcopy. At the first visit 170 women (89.0%) had a histological sample collected, 34 of whom (20.0%, 95% CI 14.3-26.8%) had CIN2 + diagnosed, 19 had CIN3 + , and two had cervical cancer). During follow-up additional CIN2 + were detected resulting in a total of 42 women (24.4%, 95% CI: 18.2-31.5%) being diagnosed with CIN2 + , 25 with CIN3 + , and three with cervical cancer. When restricting to women with paired histologic results (i.e., biopsies and a loop electrosurgical excision procedure (LEEP) specimen), we found that CIN2 + was missed in 17.9% (95% CI 8.9-30.4%) of biopsies compared to the LEEP.

Conclusion: Our findings suggest a potential risk of underdiagnosis in older postmenopausal women referred to colposcopy. Future studies should explore potential risk-markers for discrimination of women at increased risk of CIN2 + from those at low risk, as this would reduce risk of underdiagnosis and overtreatment.

Keywords: Cervical cancer screening; Cervical intraepithelial neoplasia; Colposcopy; Human papillomavirus; Loop electrosurgical excision procedure; Postmenopausal women.