Reproducibility of colposcopy quality indicators-A survey among members of the European Federation for Colposcopy.

INTRODUCTION: Colposcopy is an important part of the diagnostic work-up of women with an abnormal cervical screening test as it is used to guide the collection of biopsies. Although quality assurance has been used in the evaluation of screening programs, not much is known about quality indicators for the diagnostics and treatment of screen-positive women. Therefore, the European Federation for Colposcopy developed quality indicators aiming to support colposcopy practice across Europe. We performed a survey of colposcopy cases to determine if the quality indicators are understandable, relevant, and reproducible. MATERIAL AND METHODS: We conducted a survey among all members of the European Federation for Colposcopy Quality and Standards Group from November 2022 to March 2023. Members were asked to collect information on a total of 17 quality indicators for 50 women who had been newly referred for colposcopy due to an abnormal screening test between January 1, 2020 to December 31, 2021. Results were reported descriptively. RESULTS: We included data on 609 cases from 12 members across Europe. The majority of the quality indicators were either achieved or within reach of the agreed standard, often due to few countries with outlying data. One quality indicator had very low performance, although stratified results indicated that two countries had different clinical management of the patient type thereby skewing the results. In addition, discrepancies between the number of cases included in each quality indicator raised concerns regarding potential misunderstanding of the quality indicator and its objective. CONCLUSIONS: Quality indicators on colposcopy must be understandable to those collecting data, highlighting the importance of validating quality indicators before data collection.

Quality assurance using quality indicators for prevention and early detection of cervical cancer in certified gynaecological dysplasia units and consultancies.

PURPOSE: Cervical cancer is the fourth most common cancer in women worldwide. A successful screening concept for cervical cancer reduces the incidence and mortality of cervical cancer. Quality indicators (QIs) derived from the screening guidelines for cervical cancer and used by the certified dysplasia units and dysplasia consultancies are evaluated in this paper. The aim of this paper is to present the current data from the annual reports of these units and consultancies. METHODS: The results of the basic data and indicators for the audit year 2022 in the gynaecological dysplasia consultancies and units are presented. In 2022, 84 dysplasia consultancies and 42 units were audited. 40 units and 84 consultancies are included in the annual report. QI outcomes for patients treated in certified dysplasia units and dysplasia consultancies are analysed. Median, overall proportion, and standard deviation were calculated for each QI. RESULTS: The indicator year 2021 was analysed, which was audited in 2022 and evaluated in 2023. A total of nine QIs were analysed. Most target goals were met by the 84 certified dysplasia consultancies and by the 40 dysplasia units. The QIs evaluated are implemented to a very high degree. The targets for the three QIs were achieved by both the dysplasia consultancies and the units in at least 95% of the certified centres (QI 1: 100%, QI 2: 95%, QI 3: 100%; QI 1: 100%, QI 2: 97%, QI 3: 100%, respectively). The presentation of patients to the tumour board by the consultancies/units is working; the units are attending the tumour board more regularly than in previous years. Where the target was not met, the auditors issued deviations or reduced the duration of the certificate. The cases are discussed intensively in the sense of an individual case analysis and with the determination of measures on-site. CONCLUSIONS: The targets for the various indicators were largely met by the dysplasia consultancies and units in the 2022 audit year. The certification of gynaecological dysplasia consultancies/units which have to cooperate with certified gynaecological cancer centres, has for the first time ensured the continuity of healthcare from prevention and early diagnosis to treatment of gynaecological cancers.

HPV testing and vaccination in Europe.

Current cytology-based screening has a moderate sensitivity to detect cervical intraepithelial neoplasia grade 3 (CIN 3) and cervical cancer even in those states providing rigorous quality control of their cervical screening programs. The impact of vaccination against human papillomavirus (HPV) types 16 and 18 as well as the incorporation of HPV testing on the detection of CIN 3 and cancer is discussed. HPV testing used as a triage for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions, test of cure after treatment, and HPV-based primary screening may improve current cervical screening programs.HPV testing as a triage test for ASCUS seems to offer an improved sensitivity, with a similar specificity as compared to repeat cytology for diagnosing high-grade CIN and has been recommended throughout most EU states. HPV testing as a triage test for low-grade squamous intraepithelial lesions has a low specificity and is not recommended in most member states. HPV test of cure offers an improved sensitivity compared to cytology for women with persistent cervical precancer after treatment. HPV-based cervical cancer screening is more effective than screening with cytology. The effects of HPV-based screening depend on the organization of the program and on adherence to algorithms for screening triage. Otherwise, it is likely that HPV-based screening will increase the referral rate to colposcopy including more women with no detectable cervical lesion. HPV vaccination will require many years to evaluate any beneficial effects on cervical cancer incidence and mortality.

The future role for colposcopy in Europe.

Improvements in the performance of cervical screening may be limited by the diagnostic performance of colposcopy. Nonetheless, colposcopy remains the best available tool to assess women considered at high risk for having or developing cervical cancer. The provision and role of colposcopy across Europe is variable. Introduction of vaccination against human papillomavirus (HPV) types 16 and 18 as well as the possible switch to HPV-based screening is likely to change the profiles of women presenting to colposcopy services and provide management difficulties for the colposcopist.The standard of colposcopy in Europe can be maintained or improved despite a variable availability of screening. The prevalence of cervical intraepithelial neoplasia grade 3 may decrease for women having had HPV vaccination. The incidence of cervical intraepithelial neoplasia grade 3 and cervical cancer in second and subsequent rounds of HPV-based screening are likely to decrease compared to cytology-based screening. In HPV-based screening, the numbers of women with no detectable or minor abnormalities at colposcopy and with screen-detected glandular disease are likely to increase. We have considered how these issues will affect states that have varying implementation of organized cervical screening programs and varying degrees of implementation of HPV testing or vaccination.The development of quality assurance across Europe accompanying these program changes is discussed.

Registry Study of the Working Group on Cervical Pathology and Colposcopy (AGCPC) on the Diagnostic Algorithm for the New Cervical Cancer Screening - Initial Data.

Introduction: For the first time since 1971, new regulations were introduced for cervical cancer screening as an organized cancer screening guideline (oKFE-RL) starting 1 January 2020. From the age of 20, a cytological smear test is performed annually, and from the age of 35, so-called co-testing (cytology and test for high-risk HPVs) is performed every three years. In case of abnormalities, the algorithm is used as the basis for investigation. According to this diagnostic algorithm, even so-called low-risk groups receive early colposcopic evaluation. This approach has been heavily debated and serves as the basis for this registry study. Methods: All patients who presented to the centers for a colposcopy as part of the diagnostic algorithm were included after signing an informed consent form. The following findings were obtained: Medical history, colposcopy, histology, and cytology findings, as well as possible therapies and their findings. The aim was to evaluate the frequency of the target lesions cervical intraepithelial neoplasia (CIN) 2+/CIN 3+ in the respective groups. Result: A total of 4763 patients were enrolled in the study from July 2020 to October 2022. As a referral diagnosis, HPV persistence (HPV: human papillomavirus) with group I was determined in 23.9% (1139), HPV persistence with group II-a in 2.1% (100), II-p (ASC-US) in 11.2% (535), and II-g (AGC endocervical NOS) in 1.3% (64). III-p (ASC-H) and III-g (AGC endocervical favor neoplastic) were found in 9.4% (447) and 2.2% (107), respectively, IIID1 (LSIL) in 19% (906), IIID2 (HSIL, moderate dysplasia) in 18.9% (898), IVa-p (HSIL, severe dysplasia) in 10.7% (508), IVa-g (AIS) in 0.7% (31), IVb-p (HSIL with features suspicious for invasion) and IVb-g (AIS with features suspicious for invasion) in 0.3% (15), 0.1% (6), and 7 with suspected invasion V-p (squamous cell carcinoma)/V-g (endocervical adenocarcinoma) (0.1%). In the IVa-p group (HSIL, severe dysplasia), 67.7% had CIN 2+ and 56.5% had CIN 3+, adenocarcinoma in situ (AIS), and adenocarcinoma. If the histology of the excised tissue specifically based on the colposcope findings was also evaluated, CIN 2+ was found in 79.7% of cases, and CIN 3+ in 67.3% of cases. In IIID2 (HSIL, moderate dysplasia), CIN 2+ was detected in 50.9%, and CIN 3+/AIS in 28.3%. After evaluating patients who underwent surgery immediately, this increased to 53.0% for CIN 2+ and 29.3% for CIN 3+/AIS. In IIID1 (LSIL), CIN 2+ was detected in 27.4% and CIN 3+/AIS in 11.7%, and in II-p (ASC-US), CIN 2+ was detected in 23.4% and CIN 3+ and AIS in 10.8%, and in II-g (AGC endocervical NOS), CIN 2+ was detected in 34.4% and CIN 3+ in 23.4%. In the HPV persistence/II-a and I group, 21% showed CIN 2+, and 12.1% showed CIN 3+ and AIS, and 13% showed CIN 2+ and 5.9% showed CIN 3+ and AIS. In patients who were HPV-negative and had further diagnostics performed on the basis of cytologic smear alone, 27.9% had CIN 2+, and 14.1% had CIN 3 and AIS. Discussion: In a synopsis of the present findings of our initial data of the registry study on the new cervical cancer screening, according to the organized early cancer screening guideline (oKFE-RL), we could show that the target lesion CIN 3+ and AIS is detected unexpectedly frequently in a not insignificant proportion, especially in the cytological low-risk group. Currently, we cannot answer whether this can reduce the incidence and mortality of cervical carcinoma, but this could be an initial indication of this and will be reviewed in further long-term evaluations.

Statement of the AGO and AG-CPC on the Aftercare/Follow-up for Surgical Procedures of the Lower Genital Tract after the Introduction of a New Cancer Screening Guideline.

The new guideline on organized cancer screening programs has been in force in Germany since January 1st, 2020. The guideline has amended earlier recommendations on cytological examinations, which were previously carried out annually during screening. The guidelines-based recommendations on the appropriate follow-up for preinvasive and invasive lesions of the uterine cervix and endometrium are briefly outlined and differentiated from screening cytology and Pap/HPV co-testing as described in the guideline on organized cancer screening programs (oKFE-RL).

Human papillomavirus E6/E7 mRNA testing has higher specificity than liquid-based DNA testing in the evaluation of cervical intraepithelial neoplasia.

OBJECTIVE: To examine the specificity of human papillomavirus (HPV) E6/E7 mRNA testing for intraepithelial precursor lesions and invasive carcinoma of the uterine cervix in 358 women and compare the results with those of the most widely used DNA technique. STUDY DESIGN: For HPV E6/E7 mRNA testing an amplification assay was used. For DNA determination a hybridization assay was applied. Both techniques were used simultaneously in patients with normal morphology (150), cervical intraepithelial neoplasia (173) and invasive carcinoma of the cervix (35). RESULTS: HPV DNA positivity rates were significantly higher than E6/E7 mRNA in women with normal morphology (21-7%), cervical intraepithelial neoplasia (CIN) 1 and 2 (75-43%), and CIN 3 (93-63%). In invasive cervical carcinoma, both methods tested equally high (94% vs. 97%). Considering that E6/E7 up-regulation represents the initial step in cervical carcinogenesis, it can be assumed that this test allows a more specific detection of lesions with a potential for progression. CONCLUSION: HPV E6/E7 mRNA may serve as a more specific discriminator between transient cervical dysplasias and potentially progressive lesions. Accordingly, testing for high-risk HPV E6/E7 mRNA might reduce the psychologic burden associated with HPV-DNA testing.

Randomized phase III trial of topotecan following carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO.

BACKGROUND: The combination of carboplatin and paclitaxel is the standard of care for the treatment of ovarian cancer, yet rates of recurrence and death remain high. We performed a prospective randomized phase III study to examine whether sequential administration of topotecan can improve the efficacy of carboplatin and paclitaxel in first-line treatment of advanced epithelial ovarian cancer. METHODS: A total of 1308 patients with previously untreated ovarian cancer (International Federation of Gynecology and Obstetrics stages IIB-IV) were randomly assigned to receive six cycles of paclitaxel and carboplatin followed by either four cycles of topotecan (TC-Top; 658 patients) or surveillance (TC; 650 patients) on a 3-week per cycle schedule. The primary endpoint was overall survival, and secondary endpoints were progression-free survival, response rate, toxicity, and quality of life. Time-to-event data were analyzed using the Kaplan-Meier method, and a stratified log-rank test was used to compare distributions between treatment groups. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model. Categorical data were compared using a stratified Cochran-Mantel-Haenszel test. All statistical tests were two-sided. RESULTS: Median progression-free survival was 18.2 months in the TC-Top arm versus 18.5 months in the TC arm (stratum-adjusted HR = 0.97 [95% CI = 0.85 to 1.10]; P = .688). Median overall survival was 43.1 months for the TC-Top arm versus 44.5 months for the TC arm (stratum-adjusted HR = 1.01 [95% CI = 0.86 to 1.18]; P = .885). At 3 years, overall survival in both arms was 57% (58.5% in the TC arm and 55.7% in the TC-Top arm). Compared with patients in the TC arm, patients in the TC-Top arm had more grade 3-4 hematologic toxic effects (requiring more supportive care) and more grade 3-4 infections (5.1% versus 2.7%; P = .034) but did not have a statistically significant increase in febrile neutropenia (3.3% versus 3.1%; P = .80). Among patients who had measurable disease (TC, n = 147; TC-Top, n = 145), overall (i.e., complete or partial) response was 69.0% (95% CI = 61.4% to 76.5%) in the TC-Top arm and 76.2% (95% CI = 69.3% to 83.1%) in the TC arm (P = .166). CONCLUSIONS: The sequential addition of topotecan to carboplatin-paclitaxel did not result in superior overall response or progression-free or overall survival. Therefore, this regimen is not recommended as standard of care treatment for ovarian cancer.