Germline variants of homology-directed repair or mismatch repair genes in cervical cancer.

While cervical cancer is associated with a persistent human papillomavirus (HPV) infection, the progression to cancer is influenced by genomic risk factors that have remained largely obscure. Pathogenic variants in genes of the homology-directed repair (HDR) or mismatch repair (MMR) are known to predispose to diverse tumour entities including breast and ovarian cancer (HDR) or colon and endometrial cancer (MMR). We here investigate the spectrum of HDR and MMR germline variants in cervical cancer, with particular focus on the HPV status and histological subgroups.

Validation and functional follow-up of cervical cancer risk variants at the HLA locus.

Cervical cancer is the fourth most common cancer in females. Genome-wide association studies (GWASs) have proposed cervical cancer susceptibility variants at the HLA locus on chromosome 6p21. To corroborate these findings and investigate their functional impact in cervical tissues and cell lines, we genotyped nine variants from cervical cancer GWASs (rs17190106, rs535777, rs1056429, rs2763979, rs143954678, rs113937848, rs3117027, rs3130214, and rs9477610) in a German hospital-based series of 1122 invasive cervical cancers, 1408 dysplasias, and 1196 healthy controls.

Association of two genomic variants with HPV type-specific risk of cervical cancer.

Problem: Human papillomavirus infection is integral to developing invasive cervical cancer in the majority of patients. In a recent genome-wide association study, rs9357152 and rs4243652 have been associated with seropositivity for HPV16 or HPV18, respectively. It is unknown whether these variants also associate with cervical cancer triggered by either HPV16 or HPV18.

Genome-wide association study and functional follow-up identify 14q12 as a candidate risk locus for cervical cancer.

Cervical cancer is among the leading causes of cancer-related death in females worldwide. Infection by human papillomavirus (HPV) is an established risk factor for cancer development. However, genetic factors contributing to disease risk remain largely unknown.

Significant decline of HPV 6 infection and genital warts despite low HPV vaccination coverage in young women in Germany: a long-term prospective, cohort data analysis.

Background: The introduction of human papillomavirus (HPV) vaccination has resulted in a remarkable decline of genital warts in women and men, but in Germany historical rates of vaccination are relatively low. We report long-term surveillance data on changes in HPV 6 and HPV 11 infection and the prevalence of genital warts in young women in the Wolfsburg HPV epidemiological study (WOLVES).

Methods: Women born in 1983/84, 1988/89, and 1993/94 participated in four cohorts between 2009/10 and 2014/15.

Association of genomic variants at PAX8 and PBX2 with cervical cancer risk.

Cervical malignancy is triggered by human papillomavirus infection but the risk for cervical cancer has a hereditary component. From a recent Genome Wide Association Study meta-analysis, 2q14.1 (PAX8) and 6p21.

Association of genomic variants at the human leukocyte antigen locus with cervical cancer risk, HPV status and gene expression levels.

The human leukocyte antigen (HLA) locus on chromosome 6 has been reported to be associated with cervical cancer. We investigated two independent single-nucleotide polymorphisms in a large case-control series of cervical dysplasia and carcinoma that has been newly established by the German Cervigen Consortium, comprising a total of 2481 cases and 1556 healthy females. We find significant associations for both variants, rs9272117 at HLA-DQA1 and rs2844511 at MICA and HCP5, with cervical disease.

Reduction of cervical cancer incidence within a primary HPV screening pilot project (WOLPHSCREEN) in Wolfsburg, Germany.

Background: Randomised controlled trials showed human papillomavirus (HPV)-based screening leads to a significant reduction in cervical cancer incidence compared with cytology-based screening only.

Methods: Non-hysterectomised participants ≥30 years underwent co-testing with Papanicolaou (Pap) smear and HR-HPV testing (Hybrid Capture 2; HC2). Women with normal findings had their next screening round after 5 years, and HC2+ and Pap abnormal cases were immediately referred for colposcopy, while cases with discordant findings had repeat testing after 12 months with referral to colposcopy in cases with persistent positive findings.

Surgical staging identified false HPV-negative cases in a large series of invasive cervical cancers.

Objective: We examined a large series of biopsy-proven invasive cervical cancers with surgical staging and HPV re-testing to estimate the relevance of HPV-negative cervical cancers in a Caucasian population.

Methods: We prospectively collected smears from 371 patients with a biopsy-proven diagnosis of cervical cancer for HC2 testing of high-risk HPV (HR-HPV). In HC2-negative cases, smears and paraffin embedded tissue blocks underwent additional HPV genotyping.

Role of tumour-free margin distance for loco-regional control in vulvar cancer-a subset analysis of the Arbeitsgemeinschaft Gynäkologische Onkologie CaRE-1 multicenter study.

Aim Of The Study: A tumour-free pathological resection margin of ≥8 mm is considered state-of-the-art. Available evidence is based on heterogeneous cohorts. This study was designed to clarify the relevance of the resection margin for loco-regional control in vulvar cancer.

Utility of EFC quality indicators for colposcopy in daily practice: results from an independent, prospective multicenter trial.

Objectives: The accuracy of colposcopy as the gold standard to manage abnormal screening tests depends on qualification and well defined standards. A recent survey of the European Federation for Colposcopy (EFC) found strong heterogeneity in the practice of colposcopy across Europe. EFC defined four quality indicators (QIs) to enable quality assessment in colposcopy as one tool to harmonize colposcopy standards.

Incidence patterns and temporal trends of invasive nonmelanotic vulvar tumors in Germany 1999-2011. A population-based cancer registry analysis.

Objectives: Time trends on the incidence and characteristics of invasive vulvar cancer in Germany have so far been studied in few local population- and hospital based tumor registries. We aimed to provide an overview on recent developments of vulvar cancer in Germany, using population-based cancer registry data.

Methods: We analyzed the data on vulvar cancer of eight population-based German cancer registries for the period 1999-2011.

Laser-skinning colpectomy for extended vaginal intraepithelial neoplasia and microinvasive cancer.

Objective: The aim of this study is to analyze the efficacy of colposcopic-guided laser-skinning colpectomy to treat extended high-grade vaginal intraepithelial neoplasia (VaIN).

Methods: Retrospective review of 33 heavily pretreated patients with high-grade VaIN extending over 20-100% of the vaginal surface treated between 2003 and 2013 with colposcopic-guided laser-skinning colpectomy. The vaginal epithelium including all VaIN lesions was excised in one piece with a depth of 2-3mm.

Utility and Reproducibility of the International Federation for Cervical Pathology and Colposcopy Classification of Transformation Zones in Daily Practice: A Multicenter Study of the German Colposcopy Network.

Objective: To compare the distribution of International Federation for Cervical Pathology and Colposcopy (IFCPC) transformation zone (TZ) types among women in different age groups referred to 8 colposcopy clinics.

Materials And Methods: Between February 2012 and February 2013, we prospectively collected individual patient data from 8 clinics within the German Colposcopy Network (G-CONE). Data were analyzed using ODSdysplasie, software designed to allow continuous quality assessment in colposcopy clinics.

Efficacy and safety of hexaminolevulinate photodynamic therapy in patients with low-grade cervical intraepithelial neoplasia.

Objective: Non-surgical therapies are needed to reduce the rate of progression of low-grade cervical intraepithelial neoplasia (CIN 1) to high grade CIN (CIN 2/3). The aim of this study was to assess the efficacy and safety of hexaminolevulinate (HAL) photodynamic therapy (PDT) in the treatment of patients with CIN 1.

Study Design: This phase IIa prospective double-blind study randomized patients with CIN 1 into three groups: HAL vaginal suppository, placebo vaginal suppository or follow-up only.

Early detection of CIN3 and cervical cancer during long-term follow-up using HPV/Pap smear co-testing and risk-adapted follow-up in a locally organised screening programme.

We evaluated compliance with human papillomavirus (HPV) testing and risk-adapted patient pathways and monitored changes in high-grade cervical disease during long-term follow-up. Women aged >30 years attending routine screening for cervical cancer were managed according to results from first-round screening tests (cytology and high-risk HPV; Hybrid Capture 2). Between February 2006 and January 2011, 19,795 of 19,947 women agreed to participate, of whom 4,067 proceeded to a second screening round 5 years after recruitment.

Treatment of extramammary Paget disease of the vulva with imiquimod: a retrospective, multicenter study by the German Colposcopy Network.

Background: Extramammary Paget disease (EMPD) is a very rare genital neoplasia associated with a high frequency of local recurrences. Surgical excision is the standard treatment, but results in mutilating procedures in patients with advanced or recurrent disease. Case reports have shown clinical responses to imiquimod in patients with EMPD, but this therapy has not been evaluated systematically.

Annual Papanicolaou screening for 5 years among human papillomavirus-negative women.

Background: Primary human papilloma virus (HPV) screening is more effective than cytology in reducing the risk of cervical cancer, but screening intervals should be extended in HPV-negative women. However, some Markov models predicted that long intervals are associated with an excess risk of cervical cancer. The aim of this analysis was to estimate the real-life risks and benefits of annual Papanicolaou (Pap) screening in HPV-negative women with normal cytology.

Prevalence of high-risk HPV types and associated genital diseases in women born in 1988/89 or 1983/84--results of WOLVES, a population-based epidemiological study in Wolfsburg, Germany.

Background: High-risk human papilloma virus (HR-HPV) infection is associated with the development of cervical cancer. HPV vaccination reduces the risk of developing malignant lesions and is expected to change the dynamics of HPV transmission. Data from non-vaccinated women may provide an important benchmark to allow the impact of HPV vaccination programs to be assessed.

Prevalence of low-risk HPV types and genital warts in women born 1988/89 or 1983/84 -results of WOLVES, a population-based epidemiological study in Wolfsburg, Germany.

Background: Wolfsburg HPV Epidemiological Study (WOLVES) is a population-based cohort study on HPV infections and associated diseases in the pre-vaccination era in young women in Wolfsburg, Germany.

Methods: Women born 1983/84 or 1988/89 were invited to participate. Participants were recruited in gynecology practices, and completed a questionnaire with socioeconomic, sexual and medical data including vaccination status.

Accuracy of colposcopy management to detect CIN3 and invasive cancer in women with abnormal screening tests: results from a primary HPV screening project from 2006 to 2011 in Wolfsburg, Germany.

Objective: Combining HPV and Pap screening achieves very good risk stratification and sensitive detection of CIN3 and cancer (CIN3 +), but poorer specificity, and may result in an increased risk of glandular and new lesions during follow-up. We examined if this phenomenon may compromise the accuracy of colposcopy.

Methods: As part of a primary HPV screening pilot project comprising 19,624 participants aged over 30 years, the failure rate to detect CIN3 at first visit was measured over a five-year period to assess the quality of colposcopy as an overall management concept.