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

Abstract

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.

Assessment of Human Papillomavirus Non-16/18, Type-Specific Risk for Cervical Intraepithelial Neoplasia Grade 3 or Worse Among Women With Cervical Atypical Glandular Cells

“…We previously reported extremely high invasive cervical cancer risks for women with HPV16/18–positive AGC (17%). 8 By contrast, the invasive cervical cancer risk among women with “other” HPV was only 1.5% (5/341) and was zero for all other HPV types except HPV45 and 31. The results from this study provide greater knowledge on the risks associated with different HPV types therefore emphasize the need for careful management.…”

“…Most AIS and invasive cervical cancer cases were related to HPV45. If we also include the women who tested positive for HPV16/18 in the index sample analysis, 8 HPV18, 16, and 45 (in that order) were the major HPV types associated with AIS and adenocarcinoma. Our results are in accordance with previous studies.…”

“…The study setting, design, and population have been described previously. 8 Briefly, all women aged 23 years or older residing in the Stockholm-Gotland region of Sweden who had an AGC diagnosis in a cervical cytologic sample between February 17, 2014, and December 31, 2018, were included. Because women are invited to population-based cervical cancer screening at the age of 23 years in Sweden, there were no women younger than age 23 years included in this study.…”

“…[5][6][7] We previously found that among the oncogenic HPV types, HPV16/18 positivity was associated with the highest cumulative incidence risk for invasive cervical cancer among women with AGC. 8 However, although many HPV tests provide results for HPV16/18, it is common for HPV tests to report oncogenic HPV types other than HPV16/18 merely as a joint category. Most HPVpositive AGC samples are typically reported as positive for other HPV.…”

“…Most HPVpositive AGC samples are typically reported as positive for other HPV. 8 This study evaluates whether the risk for cervical precancer and cancer was different among the HPV types reported as other HPV in a large populationbased cohort 8 by performing HPV genotyping on other HPV-positive samples from women with AGC in cytology. Knowledge of these risks can be used to inform AGC management strategies, that in turn might be beneficial in improving the effectiveness of cervical screening.…”