Clear cell endometrial carcinoma with high microsatellite instability in a complicated pregnancy: a case report.

BACKGROUND: Endometrial carcinomas are the most common female genital malignancies. They are very rare in pregnancy and worldwide less than 60 cases associated with pregnancy are published. No clear cell carcinoma has been described in a pregnancy with a live birth. CASE PRESENTATION: We present the course of a 43-year-old Uyghur female patient with the diagnosis of endometrial carcinoma with a deficiency in the DNA mismatch repair system in the pregnancy. The malignancy with clear cell histology was confirmed by biopsy following the delivery via caesarean section due to preterm birth of a fetus with sonographically suspected tetralogy of Fallot. Earlier whole exome sequencing after amniocentesis had shown a heterozygous mutation in the MSH2 gene, which was unlikely to be related to the fetal cardiac defect. The uterine mass was initially deemed an isthmocervical fibroid by ultrasound and was confirmed as stage II endometrial carcinoma. The patient was consequently treated with surgery, radiotherapy and chemotherapy. Six months after the adjuvant therapy, re-laparotomy was performed due to ileus symptoms and an ileum metastasis was found. The patient is currently undergoing immune checkpoint inhibitor therapy with pembrolizumab. CONCLUSION: Rare endometrial carcinoma should be included in the differential diagnosis of uterine masses in pregnant women with risk factors.

Expression of Progesterone Receptor A as an Independent Negative Prognosticator for Cervical Cancer.

The role of progesterone receptor A (PRA) for the survival outcome of cervical cancer patients is ambiguous. In mouse models, it has been shown that PRA plays a rather protective role in cancer development. The aim of this study was to assess its expression by immunohistochemistry in 250 cervical cancer tissue samples and to correlate the results with clinicopathological parameters including patient survival. PRA expression was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) classification scores. PRA was significantly overexpressed in adenocarcinomas compared to squamous epithelial carcinoma subtypes. Correlation analyses revealed a trend association with the HPV virus protein E6, a negative correlation with p16 and a positive correlation with EP3. PRA expression was also associated with the expression of RIP140, a transcriptional coregulator that we previously identified as a negative prognostic factor for survival in cervical cancer patients. Univariate survival analyses revealed PRA as a negative prognosticator for survival in patients with cervical adenocarcinoma. Multivariate analyses showed that simultaneous expression of RIP140 and PRA was associated with the worst survival, whereas with negative RIP140, PRA expression alone was associated with the best survival. We can therefore assume that the effect of nuclear PRA on overall survival is dependent upon nuclear RIP140 expression.

Trends among patients with endometriosis over a 7-year period and the impact of the COVID-19 pandemic: experience from an academic high-level endometriosis centre in Germany.

PURPOSE: Endometriosis is known to be an underestimated disease. Lately the awareness of the disease seems to have improved. Aim of this analysis is to provide an overview of the development of treatment of patients diagnosed with endometriosis. This includes a special scope on implications of the COVID-19 pandemic since in multiple settings postponed treatments resulting in negative impact on prognosis were reported. MATERIALS AND METHODS: We analysed the development of numbers of patients treated for endometriosis in an academic centre within a 7-year period, 01/2015-12/2021, performing a systematic analysis of ICD-10-Codes from our computer system used in clinical routine. RESULTS: Treatment numbers increased over the past 7 years, i.e., 239 treated cases in 2015 vs. 679 in 2021. Following restrictions for outpatient evaluation and surgical capacity at our centre, during COVID-19 pandemic the numbers of treated patients were reduced, especially in the first lockdown period (03/22/2020-05/05/2020 vs. same period in 2019: outpatient clinic (9 vs. 36; p < 0.001), patients surgically treated (27 vs. 52; p < 0,001)). The comparison of 2020 to 2019 showed a reduction in April 2020 of - 37% in outpatient department and up to - 90% for surgically treated patients. Comparing to 2019, we found a reduction of surgical interventions in 2020 by - 9% and an increase by 83% in 2021. CONCLUSIONS: Raising numbers of patients treated for endometriosis point to a new awareness for the disease. After the decline during the lockdown period numbers raised again, leading to a delay, but not an omission of treatment. A certified endometriosis centre with established and well-organized structures is required to improve not only treatment results but also quality of life of those affected.

CCL22-Polarized TAMs to M2a Macrophages in Cervical Cancer In Vitro Model.

Macrophages are dynamic cells susceptible to the local microenvironment which includes tumor-associated macrophages (TAMs) in cancers. TAMs are a collection of heterogeneous macrophages, including M1 and M2 subtypes, shaped by various activation modes and labeled with various markers in different tumors. CCL22+-infiltrating cells are thought to be significantly associated with the prognosis of cervical cancer patients. Moreover, CCL22 is an established marker of M2a macrophages. Although the phenotypic identification of M1 and M2 macrophages is well established in mice and human macrophages cultured in a medium with fetal calf serum (FCS), fewer studies have focused on M2 subtypes. In addition, the question of whether CCL22 affects polarization of M2a macrophages remains unanswered. This study constructed a co-culture system to shape TAMs in vitro. We found that CCL22 was mainly secreted by TAMs but not cervical cancer cell lines. Human peripheral blood monocytes were differentiated into uncommitted macrophages (M0) and then polarized to M1, M2a, M2b, and M2c macrophages using LPS plus IFNr, IL-4, LPS plus IL1ß, and IL-10, respectively. Using flowcytometry, we found CD80++ was the marker of M1 and M2b, CD206++ was the marker of M2a, and CD163++ was the marker of M2c, compared with M0 macrophages. By regulating CCL22, we found that the mean fluorescence intensity (MFI) of CD206 in TAMs was significantly affected compared to the control group. Therefore, CCL22 could polarize TAMs of cervical cancer toward M2a macrophages. In conclusion, our study revealed that CCL22 could be a therapeutic target for cervical cancer, which might be because of its role in regulating macrophage polarization.

Changes in gynecologic and breast cancer diagnoses during the first wave of the COVID-19 pandemic: analysis from a tertiary academic gyneco-oncological center in Germany.

PURPOSE: With the beginning of 2021, the world has been suffering from the COVID-19 pandemic for more than 1 year. More and more, we are able to evaluate side effects of the pandemic in the healthcare sector. A negative impact on cancer diagnoses is one of them. Careful observation of trends in an academic gyneco-oncological context appears important to identify potential negative developments. METHODS: We analyzed the case number of gynecologic and breast cancer diagnoses in the period from January to June 2020 compared to 2019 and during the period of the first general German lockdown (March 22nd until May 5th 2020). Patients were characterized by age, tumor type, FIGO or TNM stage and presence of symptoms at initial hospital presentation. RESULTS: The frequency of newly diagnosed gynecologic and breast cancer cases from beginning of January until end of June changed by - 10% and by - 12% during the lockdown in 2020 compared to 2019. In both periods, reduction of breast cancer cases was relatively larger than decrease of gynecologic cancers. Moreover, median patient age decreased. For the first half of 2020, we found a shift towards higher tumor stages (N+/M1 or FIGO III-IV). During the lockdown period, the appearance of tumor-associated symptoms at diagnosis increased by about 12%. CONCLUSION: This analysis illustrates the anticipated general decrease in diagnoses of primary cancers during the lockdown periods in 2020 due to COVID-19 pandemic for gynecologic and breast cancer cases.

Persistent increase of ß-hCG level after salpingectomy in tubal pregnancy: Good or bad news?

Heterotopic pregnancy is a rare event in natural conception (1:30000). We describe a case of a 36-year-old nulliparous. She presented to our department in the 4 + 6 gestational week with two simultaneous pregnancies intrauterine and extrauterine. Here, we compare treatment options and ultrasound findings to help examiners avoid inadequate therapeutic approaches.

Nuclear receptor corepressor (NCoR) is a positive prognosticator for cervical cancer.

PURPOSE: Enzymes with epigenetic functions play an essential part in development of cancer. However, the significance of epigenetic changes in cervical carcinoma as a prognostic factor has not been fully investigated. Nuclear receptor corepressor (NCoR) presents itself as a potentially important element for epigenetic modification and as a potential prognostic aspect in cervical cancer. METHODS: By immunohistochemical staining of 250 tumor samples, the expression strength of NCoR was measured and evaluated by immunoreactive score (IRS) in the nucleus and cytoplasm. RESULTS: A low expression of NCoR in our patients was a disadvantage in overall survival. Expression of NCoR was negatively correlated with viral oncoprotein E6, acetylated histone H3 acetyl K9 and FIGO status, and positively correlated to p53. CONCLUSIONS: Our study has identified epigenetic modification of tumor cells thus seems to be of relevance in cervical cancer as well for diagnosis, as a marker or as a potential therapeutic target in patients with advanced cervical carcinoma.

Lysine-specific histone demethylase 1A (LSD1) in cervical cancer.

PURPOSE: Demethylation of DNA through enzymes like LSD1 showed a crucial impact on different kind of cancers. Epigenetic modifications in cervical cancer are still not fully investigated nevertheless of high interest for a therapeutic use. METHODS: Tumor samples of 250 cervical cancer patients were immunochemically stained and evaluated based on Immunoreactive Score. Results were statistically analyzed for clinical and pathological parameters. RESULTS: Our patient collective showed a disadvantage for 10-year survival for patients with a strong expression of LSD1 in the cytoplasm of cervical cancer cells. The results of the correlational analysis further revealed a negative correlation of LSD1 to G-protein coupled estrogen receptor (GPER). CONCLUSIONS: Epigenetic changes through enzymes like LSD1 may also be of interest for patients with cervical cancer. A combined therapy with other proteins relayed to cervical cancer like GPER might be of interest for future investigations.

The prostaglandin receptor EP2 determines prognosis in EP3-negative and galectin-3-high cervical cancer cases.

Recently our study identified EP3 receptor and galectin-3 as prognosticators of cervical cancer. The aim of the present study was the analysis of EP2 as a novel marker and its association to EP3, galectin-3, clinical pathological parameters and the overall survival rate of cervical cancer patients. Cervical cancer tissues (n = 250), as also used in our previous study, were stained with anti-EP2 antibodies employing a standardized immunohistochemistry protocol. Staining results were analyzed by the IRS scores and evaluated for its association with clinical-pathological parameters. H-test of EP2 percent-score showed significantly different expression in FIGO I-IV stages and tumor stages. Kaplan-Meier survival analyses indicated that EP3-negative/EP2-high staining patients (EP2 IRS score ≥2) had a significantly higher survival rate than the EP3-negative/EP2-low staining cases (p = 0.049). In the subgroup of high galectin-3 expressing patients, the group with high EP2 levels (IRS ≥2) had significantly better survival rates compared to EP2-low expressing group (IRS <2, p = 0.044). We demonstrated that the EP2 receptor is a prognostic factor for the overall survival in the subgroup of negative EP3 and high galectin-3 expressed cervical cancer patients. EP2 in combination with EP3 or galectin-3 might act as prognostic indicators of cervical cancer. EP2, EP3, and galectin-3 could be targeted for clinical diagnosis or endocrine treatment in cervical cancer patients, which demands future investigations.

Higher CCL22+ Cell Infiltration is Associated with Poor Prognosis in Cervical Cancer Patients.

The chemokine CCL22 recruits regulatory T (T-reg) cells into tumor tissues and is expressed in many human tumors. However, the prognostic role of CCL22 in cervical cancer (CC) has not been determined. This study retrospectively analyzed the clinical significance of the expression of CCL22 and FOXP3 in 230 cervical cancer patients. Immunohistochemical staining analyses of CCL22 and FOXP3 were performed with a tissue microarray. Double immunofluorescence staining, cell coculture, and ELISA were used to determine CCL22 expressing cells and mechanisms. The higher number of infiltrating CCL22+ cells (CCL22high) group was associated with lymph node metastasis (p = 0.004), Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stages (p = 0.010), therapeutic strategies (p = 0.007), and survival status (p = 0.002). The number of infiltrating CCL22+ cells was positively correlated with that of infiltrating FOXP3+ cells (r = 0.210, p = 0.001). The CCL22high group had a lower overall survival rate (OS), compared to the CCL22low group (p = 0.001). However, no significant differences in progression free survival (PFS) were noted between the two groups. CCL22high was an independent predictor of shorter OS (HR, 4.985; p = 0.0001). The OS of the combination group CCL22highFOXP3high was significantly lower than that of the combination group CCL22lowFOXP3low regardless of the FIGO stage and disease subtype. CCL22highFOXP3high was an independent indictor of shorter OS (HR, 5.284; p = 0.009). The PFS of group CCL22highFOXP3high was significantly lower than that of group CCL22lowFOXP3low in cervical adenocarcinoma, but CCL22highFOXP3high was not an independent indicator (HR, 3.018; p = 0.068). CCL22 was primarily expressed in M2-like macrophages in CC and induced by cervical cancer cells. The findings of our study indicate that cervical cancer patients with elevated CCL22+ infiltrating cells require more aggressive treatment. Moreover, the results provide a basis for subsequent, comprehensive studies to advance the design of immunotherapy for cervical cancer.

Differential prognostic relevance of patho-anatomical factors among different tumor-biological subsets of breast cancer: Results from the adjuvant SUCCESS A study.

OBJECTIVES: In breast cancer, large tumor size, positive nodal stage and a triple-negative tumor subtype are associated with reduced survival, but the interactions between these prognostic factors are not well understood. MATERIAL AND METHODS: Here we re-evaluated the impact of tumor size, nodal stage and tumor subtype on disease-free survival (DFS), overall survival (OS), distant disease-free survival (DDFS) and breast cancer specific survival (BCSS) in a retrospective analysis using data from the adjuvant SUCCESS A trial. Subgroup analyses were conducted to assess whether the effect of tumor size and nodal stage on survival depended on tumor subtype. RESULTS: Increasing tumor size, higher nodal stage and triple negative breast cancer (TNBC) were associated with unfavorable prognosis (all p < 0.001). There was no significant interaction between tumor subtype and tumor size (p > 0.5 for all four survival endpoints), but we found significant interactions between tumor subtype and nodal stage (p < 0.05 for all four survival endpoints), with no differences in survival among tumor subtypes for patients with pN0 tumors (all p > 0.05) and pronounced differences in survival among tumor subtypes for patients with positive nodal stage (all p < 0.001). CONCLUSIONS: This analysis confirms tumor size, nodal stage and tumor subtype as independent prognostic factors in high-risk early breast cancer. Nodal-positive patients with TNBC had a considerably worse outcome compared to nodal-positive patients with another tumor subtype. This underlines the importance for early detection particularly for patients with TNBC. TRIAL REGISTRATION: EudraCT 2005-000490-21; ClinicalTrials.gov Identifier: NCT02181101.

Glucocorticoid receptor in cervical cancer: an immunhistochemical analysis.

PURPOSE: Cervical cancer is one of the most frequent cancers in women worldwide. In most of all cases, a persistent HPV infection is the leading cause. HPV-specific sequences are able to bind glucocorticoid receptor (GR). Dexamethasone can increase the activity of early promoters in HPV16 and HPV18 interfering in transcription control of viral oncogenes. The aim of our study was to evaluate glucocorticoid receptor as transcriptional factor in its active form in the nucleus of in cervical cancer cells and to correlate the results with clinical patient specific parameters. METHODS: A total of 250 paraffin-embedded cervical cancer samples obtained from patients having undergone surgery for cervical cancer were used for the study. The expression of GR was immunhistochemical examined and evaluated by a semi-quantitative scoring. SPSS software was used for the statistical evaluation of staining results and survival analysis of patients with cervical cancer. RESULTS: GR is frequently expressed in cervical carcinoma tissue in favor of squamous cell carcinoma (SCC). An enhanced expression is correlated with rather small clinical stages. The expression of the GR is correlated with better overall survival and progression-free survival. CONCLUSIONS: The glucocorticoid receptor is frequently expressed in cervical carcinoma tissue in favor of squamous cell carcinoma. An enhanced expression is correlated with rather small clinical stages. The expression of the analyzed receptor is correlated with better overall survival. Further studies are needed to determine useful treatment targets for glucocorticoid receptor manipulation.

TA-MUC1 as detected by the fully humanized, therapeutic antibody Gatipotzumab predicts poor prognosis in cervical cancer.

BACKGROUND: Gatipotuzumab is a fully humanized antibody which was designed to detect a cancer-specific glyco-modification of MUC1 (termed 'TA-MUC1') and which was optimized to effectively trigger antibody-dependent-cell-mediated cytotoxicity (ADCC) in cancer cells. Clinical trials investigating therapeutic efficacy of this antibody have been published recently. The current analysis aimed to determine whether TA-MUC1-as detected by Gatipotuzumab-is expressed in cervical cancer tissue and whether binding of Gatipotuzumab is associated with clinico-pathological variables including recurrence free (RFS) and overall survival (OS). METHODS: Cervical cancer tissue (n = 250) was stained for TA-MUC1 using Gatipotuzumab employing a standardized immunohistochemistry protocol. Staining was scored by applying the IR-score. Results were binarized and tested for association to clinico-pathological parameters. RESULTS: TA-MUC1 as stained by Gatipotuzumab was detected in 188 (75.2%) out of the 250 cervical cancer cases investigated. Expression of TA-MUC1 was restricted to cancer cells and was positively correlated with viral oncoprotein E6. Membrane staining of TA-MUC1 predicted significantly reduced RFS and OS. Importantly, expression of TA-MUC1 at the cell surface identified a group of early stage cervical cancer patients with exceptional short RFS and OS. CONCLUSIONS: We report TA-MUC1-the antigen detected by Gatipotzumab-to be widely expressed in cervical cancer tissue and to localize to the cell membrane. The latter is seen as a pre-requisite to target this epitope by antibody-drug conjugates or antibodies eliciting ADCC. Since especially, membrane localization of TA-MUC1 predicted poor prognosis, evaluating Gatipotuzumab for its therapeutic efficacy in cervical cancer may turn attractive.

The G protein-coupled estrogen receptor (GPER/GPR30) may serve as a prognostic marker in early-stage cervical cancer.

BACKGROUND: Estrogen signalling is transmitted via various receptors and multiple intracellular signalling pathways. Estrogen receptor alpha (ERα)-mediated transcription of target genes has been demonstrated to be closely linked to human papilloma virus (HPV)-induced carcinogenesis in case of cervical cancer. So far, the role of non-genomic estrogen signals in cervical cancer, e.g. transmitted by the G protein-coupled estrogen receptor (GPER) remains to be rather elusive. Today's knowledge on the role of GPER in cervical cancer is sparse and-to the best of our knowledge-GPER has not been investigated in context with clinicopathological parameters or prognosis of cervical cancer. Therefore, the current study investigated whether GPER is expressed in cervical cancer tissue. Further, GPER was correlated to clinicopathological parameters, tissue markers of cervical carcinogenesis and to patient overall and recurrence-free survival. MATERIALS AND METHODS: Cervical cancer tissue was collected from 156 patients during surgery between 1993 and 2002. GPER immunostaining was performed on all the cases and correlated to clinicopathological data. More than half of all patients were diagnosed at advanced stage (FIGO II-IV 93/156; 59.6%) of disease. The large majority of patients presented with tumours of intermediate or high grade (G2-3 140/152, 92.1%). 22 cervical cancer-related deaths (22/156, 14.1%) were documented during the follow-up period. RESULTS: GPER was detected in various subcellular staining patterns. In 129/156 (82.7%) cases GPER was expressed in the tumour cell cytoplasm (GPERcyt). GPER immunopositivity at the cell membrane (GPERmem) was found in 114/156 (73.1%) cases. While co-occurrence of both membrane and cytoplasmic staining (GPERcyt + GPERmem) was detected in the majority of tissue samples (101/156; 64.7%), only few cases (14/156, 9.0%) were classified as not expressing GPER at all. GPERcyt was positively correlated with tumour grade. Statistical associations of GPER and both p16 and p53 were detected. Finally, immunopositivity of GPERcyt was predictive for favourable overall as well as recurrence-free survival in cervical cancer of early stage (FIGO I). CONCLUSION: This retrospective study reports GPERcyt to be associated with improved overall and recurrence-free survival in early-stage cervical cancer. Further investigations are needed thus to determine whether this observation may be of clinical impact. Interestingly, Raloxifene-a GPER-activating selective estrogen receptor modulator-has recently been demonstrated to be preventive for cervical cancer relapse in mice. Whether this effect is only reliant on raloxifene blocking ERα or may also be related to activation of GPER remains to be determined.

Investigation of RIP140 and LCoR as independent markers for poor prognosis in cervical cancer.

INTRODUCTION: RIP140 (Receptor Interacting Protein) is involved in the regulation of oncogenic signaling pathways and in the development of breast and colon cancers. The aim of the study was to analyze the expression of RIP140 and its partner LCoR in cervical cancers, to decipher their relationship with histone protein modifications and to identify a potential link with patient survival. METHODS: Immunohistochemical analyses were carried out to quantify RIP140 and LCoR expression in formalin-fixed paraffin-embedded tissue sections cervical cancer samples. Correlations of RIP140 and LCoR expression with histopathological variables were determined by correlation analyses. Survival rates of patients expressing low or high levels of RIP140 and LCoR were compared by Kaplan-Meier curves. RESULTS: RIP140 overexpression was associated with a significantly shorter overall survival of cervical cancer patients. This effect was significant in the squamous cell carcinoma subtype but not in adenocarcinomas. RIP140 is no longer a significant negative prognosticator for cervical cancer when LCoR expression is low. DISCUSSION: RIP140 is an independent predictor of poor survival of patients with cervical cancer. Patients with tumors expressing low levels of both RIP140 and LCoR showed a better survival compared to patients expressing high levels of RIP140. Modulation of RIP140 and LCoR may represent a novel targeting strategy for cervical cancer prevention and therapy.

The involvement of E6, p53, p16, MDM2 and Gal-3 in the clinical outcome of patients with cervical cancer.

High-risk human papilloma virus (HPV) is the leading cause of cervical cancer. HPV oncogenes are responsible for the development of malignancy, and the E6 oncoprotein that HPV expresses induces the degradation of tumour suppressor protein p53 (p53). This degradation leads to the upregulation of p16; however, unidentified proteins may also serve a role in the development and progression of cervical cancer. Therefore, the aim of the present study was to analyse the expression levels of E6, p53, p16, MDM2 proto-oncogene (MDM2) and galectin-3 (gal-3) in cervical cancer specimens. A total of 250 cervical cancer tissue slides were used. The expression of E6, p53, p16, MDM2 and gal-3 was analysed with immunohistochemical methods and a semi-quantitative scoring. SPSS software was used for the statistical evaluation of staining results and survival analysis of patients with cervical cancer. Cervical cancer specimens demonstrated significantly increased E6 staining with advanced T-status and increased International Federation of Gynecology and Obstetrics classification. E6, p53 and p16 demonstrated significantly different expression levels in squamous epithelial tissue compared with adenocarcinomas. MDM2 and gal-3 demonstrated positively correlated expression levels in cervical cancer. In addition, gal-3 expression was correlated with poor prognosis in p16-negative cases. A negative correlation between the expression of E6 and a mutated form of p53 was also identified in cervical cancer. p53 mutation was demonstrated to be common in cervical cancer, and gal-3 and MDM2 appeared to act in a combined manner in this type of tumour. As gal-3 is overexpressed in the cervical cancer tissue of patients with poor prognosis, the use of gal-3 inhibitors should be investigated in future studies.

The Prostaglandin EP3 Receptor Is an Independent Negative Prognostic Factor for Cervical Cancer Patients.

We know that one of the main risk factors for cervical cancer is an infection with high-risk human papillomavirus (HR-HPV). Prostaglandins and their receptors are very important for the tumour growth and tumour-associated angiogenesis. Little is known about the expression of the Prostaglandin E receptor type 3 (EP3) or the Prostaglandin (PG)E2-EP3 signalling in cervical cancer, so the aim of the study was to analyse the expression of the EP3 receptor in cervical cancer and find prognostic factors in relation to survival; EP3 immunohistological staining of 250 cervical cancer slides was performed and analysed with a semi-quantitative score. The statistical evaluation was performed with Statistical Package for the Social Sciences (SPSS) to evaluate the staining results and the survival analyses of the cervical cancer cases. A significant difference was observed in EP3 expression in Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stadium I versus FIGO stadium II-IV cases. High expression of EP3 (IRS ≥ 1.5) in cervical cancer patients was correlated with poor prognosis in overall survival rates. Survival in adenocarcinoma (AC) of the cervix was lower than in squamous cell carcinoma (SCC). Cox regression analysis shows that EP3 is an independent prognosticator. In this study we could show that the membrane-bound prostaglandin receptor EP3 is an independent prognosticator for cervical cancer patient survival. Targeting the EP3 receptor seems to be an interesting candidate for endocrine therapy. Therefore, more research is needed on the influence of the receptor system and its influence on cervical cancer growth.

Prevalence of human papillomavirus infection of the anal canal in women: A prospective analysis of high-risk populations.

Infection with certain types of human papillomavirus (HPV) has been associated with the development of cervical and anal cancer. Worldwide, the incidence of anal cancer has increased markedly. The present study aimed to evaluate the prevalence of HPV infection of the uterine cervix and anal canal in human immunodeficiency virus (HIV)- and non-HIV-infected risk populations. Cervical and anal HPV swabs and cytology samples were collected from 287 patients at the University Hospital of Munich, Germany between 2011 and 2013. Patients were divided into HIV-negative controls (G1) and two risk groups, including HIV-negative patients with cytological abnormalities of the cervix (G2) and HIV-infected patients (G3). Data, including clinical parameters, were analysed. The risk groups had significantly more positive results for HPV in the anus (71.03 and 83.15% for G2 and G3, respectively), as compared with G1. The predominant HPV genotypes found in the anus were high-risk HPV genotypes, which were significantly correlated with concomittant cervical HPV findings. In the risk groups, a significant association between the cytological findings and HPV detection in the cervix was found, while the results of the anus revealed no significance. The results of the present study suggested that the prevalence of HPV infection in the anal canal of risk populations is high. Furthermore, patients with abnormal cervical cytology results and HIV-infected women, irrespective of their individual cervical findings, may have a risk of concomittant anal high-risk HPV infection. Based on the predominant HPV genotypes found in the study, HPV vaccination could reduce the incidence of anal cancer. Nevertheless, high-risk patients should be intensively screened for anal squamous intraepithelial abnormalities to avoid invasive cancer stages.