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

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.