Risk of high-grade lesions after atypical glandular cells in cervical screening: a population-based cohort study

Ingrid Norman, Anders Hjerpe, Joakim Dillner, Ingrid Norman, Anders Hjerpe, Joakim Dillner

Abstract

Objectives: To determine how human papillomavirus (HPV) positivity of atypical glandular cells (AGCs) affects the predictive values for the presence of high-grade cervical lesions.

Design: Population-based cohort study.

Setting: Stockholm-Gotland region, Sweden.

Participants: Between 17 February 2014 and 30 June 2016, there were 562 women with AGC detected in a cervical sample. Registry linkages up to 30 June 2016 identified 392 women with an associated HPV test and a histopathological follow-up.

Main outcome measure: Presence of a high-grade cervical lesion in the cervical biopsy taken after the AGC smear, in relation to the HPV status of the AGC-containing index smear.

Results: The proportion of HPV-positive AGC was 56% (n=222). In this group, there were six cases of invasive cervical adenocarcinoma, 33 cases of cervical adenocarcinoma in situ and 93 cases of high-grade squamous intraepithelial lesion (HSIL), giving a positive predictive value (PPV) for a cervical high-grade lesion of 60% (132/222). Among the 170 women with HPV-negative AGC, there was one invasive cervical squamous cell cancer and four HSIL, giving an PPV for a cervical high-grade lesion of 2.9% (5/170). This group also contained five endometrial cancers and one breast cancer.

Conclusions: HPV triaging of AGC will greatly increase the predictive ability for identifying cervical high-grade lesions (OR: 48.4 (95% CI 19.1 to122.6)) and the high sensitivity (96%; 132/137 women) implies safety of primary HPV screening strategies, with regard to this subset of patients. The measurable risk for endometrial cancer among women with HPV-negative AGC (2.9%) suggests that research on screening for endometrial cancer is needed.

Keywords: cytopathology; epidemiology; gynaecology.

Conflict of interest statement

Competing interests: None declared.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
The study flow chart. AGC, atypical glandular cells; HR-HPV, high-risk human papillomavirus; LBC, liquid-based cytology; Pap, papanicolaou.
Figure 2
Figure 2
Histological findings in HPV-positive and HPV-negative AGC cases. Advanced cervical lesions were found in 60% of HPV-positive AGC cases while only in 3% of the HPV-negative ones, corresponding to a sensitivity of 96% (132/137). ADCA cx, cervical adenocarcinoma; ADCA endom, endometrial adenocarcinoma; AGC, atypical glandular cell; AIS, adenocarcinoma in situ (cervical); HPV, human papillomavirus; HSIL, high-grade intraepithelial lesion; LSIL, low-grade intraepithelial lesion; SCC, squamous cell carcinoma (cervical); WNL, within normal limits.

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