The impact of cervical screening on cervical adenocarcinoma is varied, probably as a result of the lack of information on the risk posed by the precursor Atypical glandular cells (AGC).

All 885 women in the Swedish capital region who had AGC, concurrent human papillomavirus (HPV) testing, and histology were followed up on till 2019. By subtracting 1 from Kaplan-Meier estimates, cumulative incidence proportions of cervical intraepithelial lesions grade 3 or worse (CIN3+) by HPV type were calculated. Using Cox regression, hazard ratios (HR) for CIN3+ or for invasive cancer were calculated.

Following a 2-year period of follow-up, the cumulative incidence proportions of CIN3+ in women who tested positive for HPV16/18, “other” HPV, and HPV-negative viruses, respectively, were 80% (95% CI: 74%-86%), 58% (95% CI: 50%-60%), and 10% (95% CI: 5%-18%). Among the 300 AGC-positive women with HPV16/18, 217 had CIN3+, of which 35 had invasive cervical cancer. For HPV16/18 positive AGC, the 2-year cumulative invasive cancer risk was 17% (95% CI: 12%-24%). Although HPV-negative AGC is by design not discovered by HPV screening, primary HPV screening showed a comparable yield of CIN3+ as cytology screening. Eleven of 241 women with HPV-negative AGC—mostly following clinically recommended samples—developed CIN3+.

With regard to age or sample indication, researchers did not find any significant risk differences. The low probability of CIN3+ following HPV-negative AGC suggested that initial HPV screening was safe. Given the significant risk of invasive cervical cancer following an HPV16/18 positive AGC, cervical screening should prioritize managing the result.