Nationwide Rereview of Normal Cervical Cytologies before High-Grade Cervical Lesions or before Invasive Cervical Cancer

Abstract

Sweden has experienced an unexpected >30% increase in cervical cancer incidence among women with normal cytological screening results. We therefore performed a nationwide assessment of false-negative cytology before invasive cervical cancer. The Swedish national cervical screening registry identified 2,150 normal cytologies taken up to 10 years before 903 cases of invasive cervical cancer. The 27 cytological laboratories in Sweden were asked to rereview the slides, and all of them completed the rereview. One thousand nine hundred fifteen slides were retrieved and reviewed. Abnormalities were found in 30% of the slides, and the proportion of slides that had a changed diagnosis on rereview increased on average by 3.9% per sampling year during 2001–2016 (<i>p</i> < 0.03). We also asked for rereview of normal smears taken up to 42 months before a histopathologically diagnosed high-grade squamous intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS). 19/27 laboratories responded, and out of 6,101 normal smears taken before HSIL/AIS, 5,918 were retrieved and rereviewed. The diagnosis was changed in 25% of cases. In summary, we found an increasing time trend of false-negative smears taken before invasive cervical cancer. This indicates a decreased protection of normal cytology in the screening program supporting earlier findings that this is the main reason behind the recent Swedish increase in cervical cancer. We suggest that optimal cervical cancer control may be promoted by routine nationally coordinated rereview of negative smears before high-grade cervical lesions or invasive cervical cancer.

Cervical cancer in Region Skåne, Sweden 2017–2020 after the implementation of primary HPV screening: A quality assurance audit

“…A recent study in Sweden found an increase in normal cytological screening results prior to diagnosis of invasive cervical cancer, suggesting decreased protection from a benign cytology result due to inadequate cytological diagnosis 6 . This may to some extent be solved with HPV screening, which has proven to have a higher sensitivity compared with cytology 12 .…”

“…The cervical cancer screening program was introduced in Sweden in 1967 6 . It has contributed to a substantial decline in cervical cancer incidence and mortality 7,8 .…”

“…The coverage ratio for cervical cancer screening in the southern part of Sweden (Region Skåne) in 2017 was 78% and increased to 82.1% in 2021 10 . In 2009, the conventional Papanicolaou (Pap) smear was replaced by liquid‐based cytology (LBC), thus enabling HPV analysis and cytology on the same sample 6 …”

Audit of laboratory sensitivity of human papillomavirus and cytology testing in a cervical screening program

“…By comparison, rereviews of normal cytology taken before cervical cancer found that about 30% of slides were discrepant (did not have the same diagnosis on rereview). 23 In summary, we report a large laboratory audit of the testing within the cervical screening program. The fact that we found a consistently high sensitivity should not be taken as evidence that quality control is not needed.…”

Long‐term follow‐up of cervical cancer incidence after normal cytological findings

“…8 A nationwide re-review of normal cytology tests before invasive cervical cancer found a significant increase of false-negative cytology over time, with the proportion increasing on average by 4% per sampling year during 2001 to 2016, suggesting a continuously decreasing protection of cytology over a decade. 9 This problem affects cervical cancer prevention not only in the historical period when cytology was the primary test, but also threatens HPV-based screening as cytology in many settings remains the triage test after HPV-positive findings.…”