Implementation of quality indicators for vulvar cancer in gynaecological cancer centres certified by the German Cancer Society (DKG).

PURPOSE: In 2018, the first guideline-based quality indicators (QI) for vulvar cancer were implemented in the data-sheets of certified gynaecological cancer centres. The certification process includes guideline-based QIs as a fundamental component. These indicators are specifically designed to evaluate the level of care provided within the centres. This article aims to give an overview of the developing process of guideline based-QIs for women with vulvar cancer and presents the QIs results from the certified gynaecological cancer centres. METHODS: The QIs were derived in a standardized multiple step process during the update of the 2015 S2k guideline "Diagnosis, Therapy, and Follow-Up Care of Vulvar Cancer and its Precursors" (registry-number: no. 015/059) and are based on strong recommendations. RESULTS: In total, there are eight guideline-based QIs for vulvar cancer. Four QIs are part of the certification process. In the treatment year 2021, 2.466 cases of vulvar cancer were treated in 177 centres. The target values in the centres for pathology reports on tumour resection and lymphadenectomy as well as sentinel lymph nodes have increased since the beginning of the certification process and have been above 90% over the past three treatment years (2019-2021). DISCUSSION: QIs based on strong guideline recommendations, play a crucial role in measuring and allowing to quantify essential aspects of patient care. By utilizing QIs, centres are able to identify areas for process optimization and draw informed conclusions. Over the years the quality of treatment of vulvar cancer patients measured by the QIs was improved. The certification system is continuously reviewed to enhance patient care even further by using the outcomes from QIs revaluation.

Impact of the Corona Pandemic on Cervical Cancer Screening Assessment.

BACKGROUND/AIM: The global impact of the COVID-19 pandemic resulted in disruptions to healthcare systems throughout the world. The numbers of cytology examinations, human papillomavirus (HPV) tests, and women referred for colposcopy decreased in many countries. There have been no reports on cervical cancer screening in Germany. This study aimed to describe changes in the numbers of colposcopies, cytology examinations, HPV tests, and histological results during the pandemic compared to the pre-pandemic years in order to evaluate the impact of the COVID-19 pandemic on cervical cancer screening. PATIENTS AND METHODS: The numbers of colposcopies, cytology examinations, HPV tests, and histologic results were analyzed retrospectively for the period January 2018 to December 2022. The 2 years period before the pandemic (2018 and 2019) were compared with the 3 years period of the pandemic (2020-2022). RESULTS: In total, 6,518 colposcopies were performed in 5,579 women. The numbers of colposcopies, cytology examinations, and high-risk HPV (hrHPV) tests increased during the pandemic years. The number of biopsies per year taken was stable (range=450-554). The relative numbers of cervical intraepithelial neoplasia (CIN) III/HSIL findings were stable, while the numbers of cervical cancers identified increased slightly from 15 (6.6%) in 2018 to 22 (7.4%) in 2022. CONCLUSION: Increases in numbers of women examined and colposcopies were observed in the years 2021 and 2022 during the pandemic, in comparison to the preceding years. These also led to increases in the figures for cytology, hrHPV, histology, and operations. The onset of the pandemic occurred in the same year as a newly organized screening program started in Germany. The increases might therefore be due to the newly organized screening system.

PD-L1 Expression and Silva Invasion Pattern in Villoglandular Adenocarcinoma of the Uterine Cervix.

Villoglandular adenocarcinoma (VGA) of the uterine cervix is a rare subtype of endocervical adenocarcinoma in young women. Between 2007 and 2020, all women with endocervical adenocarcinoma were retrospectively reviewed to find patients with VGA. Eight patients in whom pure VGA had been diagnosed were included. The mean age at initial diagnosis was 36.3 years (range 24-46). After surgical treatment, patients were followed up for 59 months (range 16-150). To date, all patients are alive with no evidence of disease. Neither lymph node involvement nor lymphovascular invasion was found. Furthermore, we examined the samples with a focus on morphological invasion pattern (Silva), stromal tumor-infiltrating lymphocytes (sTILs), and immunohistochemical programmed death ligand-1 (PD-L1) expression. PD-L1 expression was observed in 7/8 using the combined positive score (cutoff≥1%), 1/8 of VGAs using the tumor proportion score (cutoff≥1%), and 7/8 using the immune cell (cutoff≥1%). Using combined positive score and immune cell, PD-L1 expression was seen in 7/8 of pattern B and C tumors, with significantly higher expression in tumors with destructive-type patterns (P<0.05, A vs. B+C). Using tumor proportion score, no significant difference in PD-L1 expression was seen between VGAs with different invasion patterns. VGAs demonstrated twice higher sTILs in tumors with destructive-type invasion patterns. Our observations suggest that PD-L1 expression, tumor invasion patterns, and sTILs do not correlate with the excellent prognosis of pure VGA.

Cytology and HPV Co-Testing for Detection of Vaginal Intraepithelial Neoplasia: A Retrospective Study.

(1) Background: Vaginal intraepithelial neoplasia (VaIN) is a rare premalignant disease caused by persistent human papillomavirus (HPV) infection. Diagnosing VaIN is challenging; abnormal cytology and positive HPV tests are usually the first signs, but published data on their accuracy for detecting it are rare and contradictory. The aim of this study is to compare the results of hrHPV and cytology co-testing with the histological findings of the vagina. (2) Methods: In the certified Dysplasia Unit at Erlangen University Hospital, cytology and HPV samples from the uterine cervix or vaginal wall after hysterectomy were obtained between 2015 and 2023 and correlated with histological findings in biopsies from the vaginal wall. Women without vaginal biopsy findings or concomitant cervical disease were excluded. (3) Results: In all, 279 colposcopies in 209 women were included. The histological results were: benign (n = 86), VaIN I/vLSIL (n = 116), VaIN II/vHSIL (n = 41), VaIN III/vHSIL (n = 33), and carcinoma (n = 3). Accuracy for detecting VaIN was higher in women with previous hysterectomies. Positive HPV testing during colposcopy increased the likelihood for VaIN II/III/vHSIL threefold. The detection rate for VaIN III/vHSIL was 50% after hysterectomy and 36.4% without hysterectomy. (4) Conclusions: Women with risk factors for VaIN, including HPV-16 infection or prior HPV-related disease, need careful work-up of the entire vaginal wall. Hysterectomy for HPV-related disease and a history of cervical intraepithelial neoplasia (CIN) also increased the risk for VaIN II/III/vHSIL.

Standardized Procedures for Patients with Dysplasia and Other Diseases of the Cervix, Vulva, and Vagina at a Certified Dysplasia Unit Prior to the Introduction of the Organized Cervical Cancer Screening Program.

Introduction Gynecologic dysplasia units and dysplasia consultations are obliged to offer diagnosis and treatment in accordance with the guidelines. The organization of the consultation process, management of patient appointments, diagnosis, and treatment algorithms are heterogeneous. The legislation arising from the new Federal Joint Committee decision, dated 22 November 2018, concerning the organized cervical cancer screening program has been in force since 1 January 2020. In this article we provide an overview of the existing structures and interdisciplinary cooperation of specialized dysplasia units incorporated in certified gynecologic cancer center. Materials and Methods We carried out a retrospective database search of data collected prospectively from 1 July 2014 to 31 December 2019 at the dysplasia unit at the Department of Gynecology and Obstetrics, Erlangen University Hospital, which was the first dysplasia unit to be certified in 2014. Results A total of 5594 patients presented at the unit, and 16061 colposcopic, vulvoscopic, and anoscopic examinations were performed. Approximately 4100 examinations of the cervix, vagina, vulva, and anus are carried out each year, 1600 of these were exclusively cervix colposcopies. A total of 12197 cytology results were assessed, as well as 4850 histology results, and 8193 high-risk HPV tests. The quality indicators required by the dysplasia unit for annual recertification were met each year. Conclusion Certified dysplasia units and consultations form the central component in the algorithm for further investigating abnormal screening results; but they are also the first point of contact for a large number of patients with acute or chronic complaints in the genital region.

Implementation and update of guideline-derived quality indicators for cervical cancer in gynecological cancer centers certified by the German Cancer Society (DKG).

PURPOSE: In 2008, the first gynecological cancer centres were certified by the German Cancer Society (DKG). Guideline-based quality Indicators (QIs) are a core element of the certification process. These QI are defined to assess the quality of care within the centres and can serve to measure the implementation of guideline recommendation. This article aims to give an overview of the developing and updating process of guideline based-QIs for women with cervical cancer and presents the QI results from the certified gynaecological cancer centres. METHODS: The QIs are derived in a multiple step review process and then implemented in the certification data sheet of the certified centres. The first set of QIs created in 2014 was revised in the update process of the S3-Guideline in 2020. QIs are based on strong recommendations of the evidence-based "Guideline for patients with Cervical Carcinoma" (registry-number: 032/033OL). RESULTS: In total, there are nine guideline-based QIs for cervical cancer. Four QIs are part of the certification process. In the treatment year 2020, 3.522 cases of cervical cancer were treated in 169 centers. The target values for the four QIs were met in at least 95% of the certified centers. In the guideline update in 2020, a new QI was added to the set of QIs "Complete pathological report on conization findings" and the QI "Exenteration" was removed. CONCLUSIONS: QIs derived from strong recommendations of a guideline are an important tool to make essential parts of patient's care measurable and enable the centers to draw consequences in process optimization. Over the years, the number of certified centers has grown, and the quality was improved. The certification systems is under constant revision to further improve patient's care in the future, based on the results of the QI re-evaluation.

Tumor-Stroma Ratio in Colorectal Cancer-Comparison between Human Estimation and Automated Assessment.

The tumor-stroma ratio (TSR) has been repeatedly shown to be a prognostic factor for survival prediction of different cancer types. However, an objective and reliable determination of the tumor-stroma ratio remains challenging. We present an easily adaptable deep learning model for accurately segmenting tumor regions in hematoxylin and eosin (H&E)-stained whole slide images (WSIs) of colon cancer patients into five distinct classes (tumor, stroma, necrosis, mucus, and background). The tumor-stroma ratio can be determined in the presence of necrotic or mucinous areas. We employ a few-shot model, eventually aiming for the easy adaptability of our approach to related segmentation tasks or other primaries, and compare the results to a well-established state-of-the art approach (U-Net). Both models achieve similar results with an overall accuracy of 86.5% and 86.7%, respectively, indicating that the adaptability does not lead to a significant decrease in accuracy. Moreover, we comprehensively compare with TSR estimates of human observers and examine in detail discrepancies and inter-rater reliability. Adding a second survey for segmentation quality on top of a first survey for TSR estimation, we found that TSR estimations of human observers are not as reliable a ground truth as previously thought.

Management of Cervical Intraepithelial Neoplasia in Pregnant Women.

BACKGROUND/AIM: The aims of the present study were to evaluate the accuracy of colposcopic findings, investigate the way in which untreated cervical intraepithelial neoplasia (CIN) 2/3 develops during pregnancy, and identify factors associated with regression, persistence, or progression rates. PATIENTS AND METHODS: In a tertiary gynecology and obstetrics department, 655 pregnant women were seen for colposcopy. The most common reason for referral was abnormal cytology findings. The follow-up findings were analyzed retrospectively on the basis of colposcopic findings and cytological and histological tests. RESULTS: The rate of accuracy for major colposcopic findings was 89.2%. Among the colposcopic findings considered "suspicious for invasion" were invasive carcinoma in 42.9% and CIN 3 in 57.1%. The persistence of CIN 3 postpartum was 80% and the rate of progression 4.1%. The rate of regression for CIN 3 was 21.9%. For CIN 2, the rate of persistence was 37.5%, with a regression rate of 31.3%. The rate of regression was higher after vaginal delivery in comparison with caesarean section. CONCLUSION: The accuracy rate of colposcopy is comparatively high, at 89.2%. This might be because pregnant women are seen by more experienced examiners in our dysplasia unit. The rate of progression is comparable with that in other studies. Vaginal delivery increases the regression rate. The newborns' birth weight or birth week did not affect the rates of regression or persistence.

Cervical intraepithelial neoplasia grade 3: development during pregnancy and postpartum.

PURPOSE: The aims of the present study were to evaluate the development of untreated cervical intraepithelial neoplasia (CIN) 3 during pregnancy and to assess persistence, progression, and regression rates postpartum to identify factors associated with regression. METHODS: In a tertiary gynecology and obstetrics department, a total of 154 pregnant women with CIN 3 were treated in the dysplasia unit. The follow-up findings were analyzed retrospectively on the basis of histological, cytological, and human papillomavirus (HPV) testing of 154 pregnant women confirmed as having CIN 3 in colposcopically guided biopsies. RESULTS: The rates of persistence, regression, and progression of CIN 3 in these women were 76.1%, 20% and 3.2%, respectively. Data for the delivery mode was available for 126 women. The rate of regression was almost twice as high with vaginal delivery as with cesarean section, at 27.4 vs. 15.2%, whereas the rate of progression was lower with vaginal delivery, at 2.7 vs. 6.5%. CONCLUSION: The rate of persistence of CIN observed in this study is comparable to that reported in other studies. The study provides strong evidence for greater regression among women who have vaginal deliveries. Careful work-up is recommended postpartum for this group of women in order to rule out persistent CIN 3 or invasive disease.

Concordance Rate of Colposcopy in Detecting Cervical Intraepithelial Lesions.

Background: The purpose of this research is to estimate the rate of concordance, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of colposcopy for high-grade squamous lesions and carcinomas (HSIL+). Methods: We conducted a retrospective study of colposcopies performed in the certified Dysplasia Unit in Erlangen between January 2015 and May 2022 (7.5 years). The colposcopic findings were correlated with biopsies obtained during examinations or surgery. Cases without histology were excluded. The primary outcome was the rate of concordance between the colposcopic and histological findings in relation to the type of transformation zone (TZ), examiner's level of experience and age of the patients. Results: A total of 4778 colposcopies in 4001 women were analyzed. The rates of concordance for CIN I/LSIL, CIN II/HSIL, CIN III/HSIL, and carcinoma were 43.4%, 59.5%, 78.5%, and 53.9%, respectively. The rate of concordance was lowest for TZ3 and highest for colposcopists with more than 10 years' experience. Conclusions: Colposcopy is an important, feasible, and effective method. Careful work-up needs to be performed for women with TZ3 who are over 35 years old, as they are at the highest risk of being misdiagnosed. The highest concordance for detecting HSIL+ was seen for colposcopists with >10 years' experience.

Cytology and High-Risk Human Papillomavirus Test for Cervical Cancer Screening Assessment.

Background: A new nationwide screening strategy was implemented in Germany in January 2020. No data are available for women referred to certified dysplasia units for secondary clarification after primary diagnosis by a local physician. We therefore investigated combined testing with Papanicolaou smears and high-risk human papillomavirus (hrHPV) and compared the data with the final histological findings. Methods: Between January 2015 and October 2020, all referred women who underwent colposcopy of the uterine cervix in our certified dysplasia unit were included. Cytology findings were classified using the Munich III nomenclature. Results: A total of 3588 colposcopies were performed in 3118 women, along with Pap smear and hrHPV co-testing, followed by histology. Women with Pap II-p (ASC-US) and a positive hrHPV co-test had a 22.4% risk for cervical intraepithelial neoplasia (CIN) 3/high-grade squamous intraepithelial lesion (HSIL). The risk of CIN 3/HSIL was 83.8% in women with Pap IVa-p (HSIL) and a positive hrHPV co-test. A positive hrHPV co-test increased the risk for HSIL+ (OR 5.942; 95% CI, 4.617 to 7.649; p < 0.001) as compared to a negative hrHPV co-test. Conclusions: The accuracy of Pap smears is comparable with the screening results. A positive hrHPV test increases the risk for HSIL+ fivefold. Colposcopy is necessary to diagnose HSIL+ correctly.

The Diagnosis, Treatment, and Aftercare of Cervical Carcinoma.

BACKGROUND: Approximately 4380 cases of cervical carcinoma were diagnosed in Germany in 2016. In women who had not participated in early detection programs, cervical carcinoma was usually already in an advanced stage at the time of diagnosis. Certified structures for care in conformity with the existing guidelines are available. METHODS: The new German clinical practice guideline was revised with the participation of 50 medical societies under the expert guidance of the Guideline Program in Oncology, which includes the German Association of the Scientific Medical Societies (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). A systematic literature review was conducted. Systematic reviews, meta-analyses, and randomized controlled trials (RCTs) were considered. RESULTS: The histologic tumor stage and lymph-node stage are essential determinants of the treatment strategy. The main innovation regarding surgical treatment is the revival of open hysterectomy (overall survival [minimally invasive vs open hysterectomy]: 94.04% vs 99.4%; hazard ratio [HR]: 6.00; 95% confidence interval [1.77; 20.30]). In addition, for tumors measuring 2 cm or less, sentinel node biopsy is recommended rather than radical pelvic lymphadenectomy. MRI-guided brachytherapy is an oblig atory component of radiochemotherapy (overall survival [radiochemotherapy with vs without brachytherapy]: 58.2% vs 46.2%, p<0.001). The standard palliative treatment consists of bevacizumab combined with a platinum-containing agent (overall survival: HR: 0.77 [0.62; 0.95]; p = 0.007). CONCLUSION: Despite the introduction of new treatments, the outcome of patients with advanced cervical carcinoma has not much improved. In the surgical treatment of cervical carcinoma, the open approach is now favored. The sentinel node biopsy technique has become well established for the surgical staging of small tumors. Controlled trials are needed so that the outcome of women with cervical carcinoma, particularly in its advanced and metastatic stages, can be improved.

Human papilloma virus genotype distribution in women with premalignant or malignant lesions of the uterine cervix.

OBJECTIVE: Cervical cancer is caused by persistent infection with high-risk human papillomavirus (hrHPV). Cytology-based national screening programs have reduced the incidence and mortality of cervical cancer. Different hrHPV subtypes have different carcinogenic potentials. This study evaluated the distribution of different types of hrHPV relative to age in cervical cancer and its precursor lesions. METHODS: HPV testing was performed between November 2018 and February 2020 using the Abbott RealTime high-risk HPV assay on an Abbott m2000sp instrument. This assay separately detects HPV-16, HPV-18, and a pool of 12 additional hrHPV types (HPV-31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, and -68). RESULTS: The study included 652 women with HPV samples and biopsies of the cervix or histology samples obtained during surgery. In all, 30.8% (95% CI, 27.3-34.6%) were HPV-negative. Among HPV-positive women, HPV-16, HPV-18, and "HPV other" types were found in 33.5, 4.4, and 49.4%, respectively. Cervical intraepithelial neoplasia (CIN) 3/high-grade squamous intraepithelial lesions (HSILs) in women ≤ 34 years were positive for HPV-16 in 54.5% of cases and in those ≥ 35 years in 45.4% of cases. Among women with cervical cancer, 75.8% were infected with HPV-16 or had coinfection with HPV-16 and "HPV other". CONCLUSIONS: HPV-16 is the most common type of hrHPV in HSIL + lesions. It is more common in women diagnosed with CIN 3/HSIL who are aged ≤ 35 and is decreasing with age. Therefore, women age ≥ 35 with persistent infection with this type of hrHPV need careful surveillance, as they are at high risk of progression to cervical cancer.

Concordance rate of vulvoscopic findings in detecting early vulvar neoplasia.

PURPOSE: Colposcopy-guided punch biopsy is a cornerstone method for diagnosing vulvar diseases. The aim of this study was to evaluate the concordance rate of clinical findings in vulvar diseases during examinations, in comparison with colposcopy-directed punch biopsy. We also developed a new classification to simplify the categorization of vulvoscopic findings. METHODS: The concordance rate of the clinical findings was compared with the final histology results from punch biopsies. The data were collected between January 2014 and May 2017 at the Erlangen University Hospital. RESULTS: A total of 482 colposcopy-directed punch biopsies of the vulva were obtained in 420 women. The overall concordance rate of the clinical findings in comparison with the histological vulvar punch-biopsy findings was 53.9% for all entities - benign lesions, lichen, low- and high-grade squamous intraepithelial lesions (LSIL/HSILs), and vulvar carcinoma. The concordance rate for detecting LSILs was 64.3% (45/70). The concordance rate for detecting HSILs was 62.3% and for Vulvar carcinoma 65.2%. CONCLUSIONS: Punch biopsy of suspicious lesions continues to be a cornerstone in diagnosing HSILs and carcinoma of the vulva. Careful work-up of the vulva is recommended when patients have symptoms such as pruritus or pain. The new classification is more specific for diagnosing lesions in the vulva.

Accuracy of colposcopic findings in detecting vaginal intraepithelial neoplasia: a retrospective study.

PURPOSE: Malignancies of the vagina are rare, but colposcopy-directed biopsies play a major role in detecting vaginal intraepithelial lesions. Data of accuracy in detecting neoplasia of the vagina are very rare compared to accuracy in detecting cervical neoplasia. The aim of this study was to evaluate the accuracy of colposcopy-directed biopsy in comparison with clinical findings of the examiner. METHODS: The accuracy of colposcopy-directed biopsy was compared with the clinical finding in relation to the patient's age and the examiner's level of training. This was done in combination with PAP-smear, HPV-test results, and the history of other malignancies of the lower genital tract. The data were collected between January 2014 and February 2018 at the certified Dysplasia Unit of the University Hospital Erlangen. RESULTS: In total, 253 biopsies from 253 women from the vagina were obtained. The overall accuracy of biopsy in comparison with clinical finding was 52.17% for all entities-benign lesions, low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs), and vaginal carcinoma. The accuracy for detecting HSIL was 82.46% (47/57), with an underdiagnosis rate of 15.79% and an overdiagnosis rate of 1.79%. CONCLUSION: With a sensitivity of over 80%, colposcopy-directed biopsy plays an important role in detecting vaginal-HSIL. A highly experienced practitioner is increasing the sensitivity in detecting vaginal-HSIL. Careful examination is required in women with a history of HSIL of the lower genital tract or with simultaneous neoplasia because they are of greater risk of developing vaginal malignancies. The combination of careful clinical work up, PAP-smear, HPV-testing, and colposcopy-guided biopsy is crucial in detecting vaginal-HSIL.

Accuracy of colposcopy-directed biopsy in detecting early cervical neoplasia: a retrospective study.

PURPOSE: Colposcopy-directed biopsy is a cornerstone method for diagnosing cervical intraepithelial neoplasia. The aim of this study was to evaluate the accuracy of colposcopy-directed biopsy in comparison with definitive surgery. METHODS: The accuracy of colposcopy-directed biopsy was compared with the final histology in relation to different types of transformation zone (TZ), the patient's age, and the examiner's level of training. RESULTS: The overall accuracy of biopsy in comparison with definitive surgery was 71.9% for all entities-benign lesions, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions (HSILs), and cervical carcinoma-with an underdiagnosis rate of 11.8% and an overdiagnosis rate of 16.5%. The accuracy for detecting HSIL was 88% (401/455), with an underdiagnosis rate of 10.5% and overdiagnosis rate of 1.3%. The accuracy rates for detecting HSIL in women with TZ 1, TZ 2, or TZ 3 were 92.2, 90.5, and 76.5%, respectively. The accuracy rates for detecting HSIL in the different age groups were 93.1% (age 0-34), 83.6% (age 34-55), and 80% (age 55 or older). CONCLUSIONS: A combination of the colposcopic findings, cytology, human papillomavirus testing, and colposcopy-directed biopsy is necessary for the correct diagnosis of HSIL. The accuracy rate depends on the TZ and the patient's age. The examiner's level of training does not have any substantial influence on the accuracy.