Combined cervical cancer screening and the incidence of adenocarcinoma

BACKGROUND: Despite the declining incidence and mortality of cervical cancer following the introduction of the opportunistic cytological screening, a diagnostic gap persisted, particularly for adenocarcinoma, due to the lower sensitivity of conventional cytology for glandular versus squamous lesions, resulting in a stagnating or modest increase in adenocarcinoma incidence. Since 2020, combined screening with HPV testing and cytology has been recommended in Germany for women aged 35 years and older. METHODS: The present analysis is based on nationwide data from the German Cancer Registry. Women who received the diagnosis of a cervical adenocarcinoma in situ (ACIS) or invasive adenocarcinoma in the years 2016-2022 were included in the analysis. Trends in age-specific and standardized incidence in three age groups (under age 35, age 35-64, and age 65 and above) were analyzed with joinpoint regression. RESULTS: Data on 4128 women with ACIS and 6244 with invasive adenocarcinoma were evaluated. In women aged 35-64, the introduction of combined screening led to a marked increase in ACIS diagnoses (average annual increase, 17.3%; 95% confidence interval [14.9; 19.6]. The rise was particularly large in 2020, with an annual percentage change (APC) of 27.5%, [17.4; 38.5]. Over the same period, there was a decline in invasive adenocarcinomas from 2021 onward (APC -10.8%, [-22.7; 2.8]). The incidence of ACIS also rose among women aged 65 and above, while that of adenocarcinoma fell slightly. CONCLUSION: Combined screening for cervical cancer improved the early detection of preinvasive glandular lesions. There is also evidence for a reduction of invasive disease in the screened population. For the full potential of screening to be achieved, there is a need for quality-assured organized programs and additional biomarkers for HPV-negative adenocarcinoma.