The effect of different invitation models on participation in cervical cancer screening (CCS) was investigated in a randomized population-based cohort study in Germany. Participants were randomly selected via population registries and randomized into intervention Arm A (invitation letter) and Arm B (invitation letter and information brochure) or control Arm C (no invitation). The intervention and control arms were compared with regard to 3-year participation and the two invitation models were compared between intervention arms. Of the 7,758 eligible women aged 30-65 years, living in the city of Mainz and in the rural region of Mainz-Bingen, 5,265 were included in the analysis. Differences in proportions of women attending CCS were investigated and logistic regression was performed to analyze various factors influencing participation. In the intervention group, 91.8% participated in CCS compared to 85.3% in the control group (p < 0.0001), with a 6.6 percentage point increase in participation [95% confidence interval (CI) 4.6-8.6] and an adjusted odds ratio (OR) of 2.69 (95% CI 2.15-3.37). Effect estimators increased to 21.9 percentage points (95% CI 16.7-27.1) and an OR of 3.64 (95% CI 2.74-4.82), respectively, when women who participated in screening annually were excluded from the analysis. The invitation letter was particularly effective among women with lower school education, migrant women and older women. No difference in participation was found between the intervention Arm A and Arm B. An accompanying information brochure did not motivate more women to undergo CCS. However, a written invitation statistically significantly increased participation in CCS in Germany.

Background: Some countries have implemented stand-alone human papillomavirus (HPV) testing while others consider cotesting for cervical cancer screening. We compared both strategies within a population-based study. Methods: The MARZY cohort study was conducted in Germany. Randomly selected women from population registries aged ≥30 years (n = 5,275) were invited to screening with Pap smear, liquid-based cytology (LBC, ThinPrep), and HPV testing (Hybrid Capture2, HC2). Screen-positive participants [ASC-US+ or high-risk HC2 (hrHC2)] and a random 5% sample of screen-negatives were referred to colposcopy. Post hoc HPV genotyping was conducted by GP5+/6+ PCR-EIA with reverse line blotting. Sensitivity, specificity (adjusted for verification bias), and potential harms, including number of colposcopies needed to detect 1 precancerous lesion (NNC), were calculated. Results: In 2,627 screened women, cytological sensitivities (Pap, LBC: 47%) were lower than HC2 (95%) and PCR (79%) for CIN2+. Cotesting demonstrated higher sensitivities (HC2 cotesting: 99%; PCR cotesting: 84%), but at the cost of lower specificities (92%–95%) compared with HPV stand-alone (HC2: 95%; PCR: 94%) and cytology (97% or 99%). Cotesting versus HPV stand-alone showed equivalent relative sensitivity [HC2: 1.06, 95% confidence interval (CI), 1.00–1.21; PCR: 1.07, 95% CI, 1.00–1.27]. Relative specificity of Pap cotesting with either HPV test was inferior to stand-alone HPV. LBC cotesting demonstrated equivalent specificity (both tests: 0.99, 95% CI, 0.99–1.00). NNC was highest for Pap cotesting. Conclusions: Cotesting offers no benefit in detection over stand-alone HPV testing, resulting in more false positive results and colposcopy referrals. Impact: HPV stand-alone screening offers a better balance of benefits and harms than cotesting. See related commentary by Wentzensen and Clarke, p. 432

Background We investigated the uptake of opportunistic cervical cancer screening (CCS) and other risk factors and their association with cervical cancer in Germany in a case-control study. Methods and findings We recruited incident cases of cervical cancer (ICD-10 C53) diagnosed between 2012 and 2016 and matched with three population-based controls, based on age and region of residence. Cases and controls reported their CCS participation during the past ten years (frequent: every three years; no or infrequent: less than every three years) and other relevant variables. We fitted conditional logistic regression models, reporting odds ratios (OR) and 95% confidence intervals (95% CI). We report overall and stratified analyses by histologic group (squamous cell–SCC, and adenocarcinoma–AC), T category (T1 and T2+), and age (<50 and ≥50 years). We analysed 217 cases and 652 matched controls. 53.0% of cases and 85.7% of controls attended CCS frequently. In the overall adjusted model, no or infrequent participation in CCS (OR 5.63; 95% CI 3.51 to 9.04), having had more than one sexual partner (OR 2.86; 95%CI 1.50 to 5.45) and obesity (OR 1.69; 95% CI 1.01 to 2.83) were associated with cervical cancer. Twelve years of schooling (OR 0.37; 95% CI 0.23 to 0.60) and a net monthly income of €3000 or more (OR 0.50; 95% CI 0.30 to 0.82) were protective factors. In the stratified analyses, no or infrequent participation was associated with T1 (OR 4.37; 95% CI 2.48 to 7.71), T2+ (OR 10.67; 95% CI 3.83 to 29.74), SCC (OR 6.88; 95% CI 4.08 to 11.59) and AC (OR 3.95; 95% CI 1.47 to 10.63). Conclusion Although women who frequently attended CCS were less likely to develop cervical cancer, especially larger tumours, the high proportion of cases who had been frequently screened prior to diagnosis underscores the need to investigate the quality of cytology and treatment of precancerous lesions in Germany.

Background A considerable proportion of cervical cancer diagnoses in high-income countries are due to lack of timely follow-up of an abnormal screening result. We estimated colposcopy non-attendance, examined the potential factors associated and described non-attendance reasons in a population-based screening study. Methods Data from the MARZY prospective cohort study were analysed. Co-test screen-positive women (atypical squamous cells of undetermined significance or worse [ASC-US+] or high-risk human papillomavirus [hrHPV] positive) aged 30 to 65 years were referred to colposcopy within two screening rounds (3-year interval). Women were surveyed for sociodemographic, HPV-related and other data, and interviewed for non-attendance reasons. Logistic regression was used to examine potential associations with colposcopy attendance. Results At baseline, 2,627 women were screened (screen-positive = 8.7%), and 2,093 again at follow-up (screen-positive = 5.1%; median 2.7 years later). All screen-positives were referred to colposcopy, however 28.9% did not attend despite active recall. Among co-test positives (ASC-US+ and hrHPV) and only hrHPV positives, 19.6% were non-attendees. Half of only ASC-US+ screenees attended colposcopy. Middle age (adjusted odds ratio [aOR] = 1.55, 95% CI 1.02, 4.96) and hrHPV positive result (aOR = 3.04, 95% CI 1.49, 7.22) were associated with attendance. Non-attendance was associated with having ≥ 3 children (aOR = 0.32, 95% CI 0.10, 0.86). Major reasons for non-attendance were lack of time, barriers such as travel time, need for childcare arrangements and the advice against colposcopy given by the gynaecologist who conducted screening. Conclusions Follow-up rates of abnormal screening results needs improvement. A systematic recall system integrating enhanced communication and addressing follow-up barriers may improve screening effectiveness.

No abstract