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 20th, 2017, and December 31st, 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.

Evaluation of the diagnostic performance of colposcopy in the detection of cervical high-grade squamous intraepithelial lesions among women with transformation zone type 3

“…A recent observational study conducted in Denmark also revealed that most women (74.9%) have TZ3 at colposcopy, and 20.0% of women had CIN2 + diagnosed among women aged ≥ 69 referred to colposcopy due to an HPV-positive screening test. The findings also suggested a potential risk of underdiagnosis of CIN2 + in older postmenopausal women referred to colposcopy [ 24 ]. Additionally, Gustafson et al [ 11 ] found that CIN2 + detection is underestimated when comparing the proportion of CIN2 + in cervical biopsies with that in large loop excision of the transformation zone (LLETZ) specimens in women aged ≥ 45 years with TZ3.…”

A Glimmer of Hope for Patients with a T3 Transformation Zone: miRNAs Are Potential Biomarkers for Cervical Dysplasia

“…Therefore, a new, rather large, patient collective in the German cervical cancer screening has led to a high influx of patients in all centres for colposcopy. This anticipated elevated colposcopy referral rate, after the introduction of HPV screening on the one hand and the reduced sensitivity rates of colposcopy in patients with a T3 transformation zone on the other hand, poses a major controversy [13,14,35]. Endocervical curettage is often uncomfortable or painful for the patients, and the rates of additional CIN2+ diagnosis are only between 0.8 and 6% [36].…”

“…With the ageing population globally, it is anticipated to represent a growing issue in the forthcoming decades. As in the case of a type 3 transformation zone (TZ), only limited assessment of the transformation zone is possible; this may result in an increased risk of missing disease by up to twofold [12][13][14]. To improve the detection and reduce the risk of missing disease in this group of women, endocervical curettage (ECC) can be performed but remains controversial [15,16].…”

Optimal Screening and Detection Strategies for Cervical Lesions: A Retrospective Study

“…Moreover, the performance of these methods may vary depending on the prevalence and distribution of HPV types and the stage and grade of cervical lesions. In clinical practice, the patients with cervical lesion CIN2 or worse including CIN2, CIN3, and cancer (CIN2+) are at high risk of developing cancer and need active surveillance or treatment 17 , 18 . Consequently, there is a need for more context-specific guidelines for the optimal screening and detection strategies for cervical lesions.…”