Atypical glandular cells and development of cervical cancer: Population‐based cohort study

The effect of cervical screening on cervical adenocarcinoma has been variable, possibly because the risk associated with the precursor atypical glandular cells (AGC) is not well known. A cohort of all 885 women in the capital region of Sweden with AGC, a concomitant human papillomavirus (HPV) analysis, and a histopathology was followed until 2019. Cumulative incidence proportions of cervical intraepithelial lesion grade 3 or worse (CIN3+) by HPV type was determined by 1‐Kaplan‐Meier estimates. Hazard ratios (HR) for CIN3+ or for invasive cancer were estimated with Cox regression. After 2 years of follow‐up, the cumulative incidence proportions of CIN3+ were 80% (95% confidence interval [CI]: 74‐86%), 58% (95% CI: 50‐60%) and 10% (95% CI: 5‐18%) among HPV16/18 positive, “other HPV” positive and HPV‐negative women, respectively. Among the 300 women with HPV16/18 positive AGC, 217 developed CIN3+ of which 35 were invasive cervical cancer. The 2‐year cumulative invasive cancer risk for HPV16/18 positive AGC was 17% (95% CI: 12‐24%). Primary HPV‐screening had a similar yield of CIN3+ as cytology screening, albeit HPV‐negative AGC is by design not detected by HPV screening. Among 241 women with HPV‐negative AGC, 11 developed CIN3+ mostly after clinically indicated samples. We found no significant risk differences depending on age or sampling indication. The low CIN3+ risk after HPV‐negative AGC implies safety of primary HPV screening. The high risk of invasive cervical cancer after HPV16/18 positive AGC implies that management of this finding is a priority in cervical screening.