Why does cervical cancer occur in a state-of-the-art screening program?

Abstract

Background The goal of cervical screening is to detect and treat precancers before some become cancer. We wanted to understand why, despite state-of-the-art methods, cervical cancers occur related to programmatic performance at Kaiser Permanente Northern California (KPNC), where >1,000,000 women aged ≥30 years have undergone cervical cancer screening by triennial HPV and cytology cotesting since 2003. Methods We reviewed clinical histories preceding cervical cancer diagnoses to assign “causes” of cancer. We calculated surrogate measures of programmatic effectiveness (precancers/(precancers and cancers)) and diagnostic yield (precancers and cancers per 1,000 cotests), overall and by age at cotest (30–39, 40–49, and ≥50 years). Results Cancer was rare and found mainly in a localized (treatable) stage. Of 623 cervical cancers with at least one preceding or concurrent cotest, 360 (57.8%) were judged to be prevalent (diagnosed at a localized stage within one year or regional/distant stage within two years of the first cotest). Non-compliance with recommended screening and management preceded 9.0% of all cancers. False-negative cotests/sampling errors (HPV and cytology negative), false-negative histologic diagnoses, and treatment failures preceded 11.2%, 9.0%, and 4.3%, respectively, of all cancers. There was significant heterogeneity in the causes of cancer by histologic category (p<0.001 for all; p=0.002 excluding prevalent cases). Programmatic effectiveness (95.3%) and diagnostic yield were greater for squamous cell versus adenocarcinoma histology (p<0.0001) and both decreased with older ages (ptrend<0.0001). Conclusions A state-of-the-art intensive screening program results in very few cervical cancers, most of which are detected early by screening. Screening may become less efficient at older ages.

A state-wide population-based evaluation of cervical cancers arising during opportunistic screening in the United States

“…Numerous studies from around the world have found non-attendance at screening to be a key reason for the development of cancer despite the availability of cervical screening [ [17] , [18] , [19] , [20] , [21] , [22] , [23] ]. Castle et al [ 24 ] recently described the screening histories of 623 women diagnosed with cervical cancer aged ≥30 yrs. in 2003–15 in one integrated health care system (Kaiser Permanente Northern California; KPNC) in the U.S.…”

Validation of a Human Papillomavirus (HPV) DNA Cervical Screening Test That Provides Expanded HPV Typing

“…At KPNC, during the time of this analysis, women were tested by HC2 to triage equivocal cytologic results of atypical squamous cells of undetermined significance (ASC-US) (since 2001) and as a cotest with cytology for women aged 30 years and older (since 2003) (24)(25)(26). Recent KPNC protocol changes to start cotesting at age 25 were not considered in this study.…”

Risks of CIN 2+, CIN 3+, and Cancer by Cytology and Human Papillomavirus Status: The Foundation of Risk-Based Cervical Screening Guidelines

“…The KPNC/NCI guidelines cohort has been previously described. 3 Starting in 2003, women 30 to 65 years old were routinely co-tested with Hybrid Capture 2 (HC2) and cytology. The current analysis includes histopathologic end point data for women aged 25 to 77 years through 2015, comprising more than a million women's outcomes.…”