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Even if today's society is rapidly evolving there is still much that can be done. This applies in the oncological field. One of the main female health problems worldwide is represented by the gynecological cancers. Ovarian cancer is the main cause of mortality among women with gynecological cancers. Although its prevalence is lover compared to breast, uterine or cervical cancer, the mortality and morbidity rates are significantly higher. The first step in the management of ovarian cancer is represented by regular screening and rapid diagnosis. One of the most important tolls is represented by serological markers dosage in order to estimate the type of tumor before the gynecological specific intervention. There is a real need to identify correctly the ovarian cancer as early as possible in order to obtain the favorable prognosis that comes with the diagnosis in earlystage. Most of the ovarian cancers (above 90%) are represented by carcinomas which are frequently diagnosed in advanced stages. The roles of the biomarkers are to indicate the malignancy of an ovarian tumor and to predict the relapse risk. The aim of this paper is to update the indications regarding the usage of serological markers in ovarian cancers and the importance of using them for our patients. [ABSTRACT FROM AUTHOR]

MicroRNA-221/222 (miRNA-221/222, miR-221/222) is a noncoding microRNA which is widely distributed in eukaryotic organisms and deeply involved in the posttranscriptional regulation of gene expressions. According to recent studies, abnormal expressions of miR-221/222 are closely related to the occurrence and development of various kinds of malignant tumors. The role of miR-221/222 in tumor development and their potential molecular mechanism in various cancers, including liver cancer, colorectal cancer, cervical cancer, ovarian cancer, and endometrial carcinoma, are summarized and reviewed in this paper. Moreover, the potential translational biomarker role of abnormal miR-221/222 level in tumor or blood circulation for tumor diagnosis is also discussed. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of cervix commonly metastasizes to the lymph nodes of the pelvis and skin metastasis is a rare presentation even in the late stages of cervical cancer. We report here the first case of cervical cancer with skin metastasis in Saudi Arabia in a 69-year-old female that preceded the diagnosis of cervical carcinoma. Microscopic examination of the skin lesion revealed poorly differentiated squamous cell carcinoma. The patient was in stage IVB based on the International Federation of Gynecology and Obstetrics (FIGO) staging system. Due to her late presentation and advanced stage, the decision was to place the patient on palliative therapy. Later, the patient passed away due to the progression of her disease. The case reported in this paper emphasizes the need for a complete clinical assessment to rule out metastatic disease from cases with known cervical cancer and include skin examination in their follow-up. [ABSTRACT FROM AUTHOR]

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Background: Cervical cancer is preventable through screening and vaccination against high-risk human papillomavirus (hr-HPV). For a screening program to be successful it is vital that the clinical management and follow-up regime of patients with abnormal screening results is well developed and that the attendance rate for follow-up is high. The aim of the study was to analyze how effective conization with recommended follow-up was in preventing subsequent cervical cancer, and to evaluate how clinical follow-up recommendations are obeyed in the region of Skåne, Sweden. Methods: All women (n = 8835) who had undergone conization in the region of Skåne, Sweden, between the years of 2015 and 2021 were identified. Individuals with confirmed cervical cancer in the conization material were referred for additional treatment (n = 114), leaving 8721 included in the follow-up. Adherence to follow-up and cytological, histopathological and HPV status at follow-up were collected at eight, 12 and 24 months post-conization. The total follow-up time was from January 1, 2015, to January 30, 2023. Results: Within 12 months post-conization, 90% of the patients conducted a cytological cervical sample. The rates of a negative test of cure (HPV negative and normal cytology) were 69.7%, 76.3% and 84.4% at eight, 12 and 24 months post-conization respectively. The clearance of HPV was 79.6%, 80.8% and 87.8% at eight, 12 and 24 months post-conization respectively. Out of 5613 patients with a negative test of cure within one year after conization, no cervical cancer was found during follow-up and 11 (0.2%) women developed high-grade intraepithelial lesions/adenocarcinoma in situ (HSIL/AIS) with an average time from conization to new diagnosis of 42 months. The mean follow-up time was 32.1 months. Conclusions: The clearance rate of hr-HPV post cervical conization due to dysplasia appears to be high within eight months. With a negative test of cure post cervical conization, the risk of cervical cancer within the following three years seems to be extremely low and the risk of developing HSIL/AIS was lower than the incidence of HSIL/AIS in the general screening population. [ABSTRACT FROM AUTHOR]

Fusion defects of the Müllerian ducts occur frequently and they have been described by the American Fertility Society. However, septate uterus with cervical duplication and longitudinal vaginal septum is not described by this classification and has suggested a change in the classical theory of fusion of the Müllerian ducts. This paper describes a rare case report of a patient with complete septate uterus with double cervix and longitudinal vaginal septum, submitted to the vaginal septoplasty for dyspareunia, progressing to clinical improvement. The description of this case is to contribute with all uncommon cases of Müllerian anomalies reports and clinical treatment protocols, which is not yet established. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the leading causes of female death, with an annual mortality rate exceeding 200,000 in developing communities. Despite the past decade bearing witness to a reduction in cervical cancer cases throughout developed countries, the prevalence in developing countries continues to rapidly rise. The increase in cervical cancer cases is attributed to the lack of financial resources and the unavoidable risk factors of the disease. Traditional means of anticancer therapy are compromised by reduced drug potency, non-specificity, negative side effects and the development of multiple drug resistance (MDR), which leads to a decrease in the long-term anticancer therapeutic efficacy. Recent advances in nanomedicine have elucidated the potential of nanoparticles to reduce the side effects and improve the survival rate of patients, by enhancing selective delivery and uptake of photosensitive, therapeutic and genetic material to cervical cancer cells, thereby enhancing antitumour efficiency. This review paper analyses the risk factors and epidemiology of cervical cancer globally, especially in developing communities, whilst demonstrating the enhanced anticancer treatment using selected nanoparticles. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is the fourth most common cancer among women worldwide. The aim of this study is to focus on the state of the art of CC prevention, early diagnosis, and treatment and, within the latter, the role of surgery in the various stages of the disease with a focus on the impact of the LACC study (Laparoscopic Approach to Cervical Cancer trial) on the scientific debate and clinical practice. We have discussed the controversial application of minimally invasive surgery (MIS) for tumors < 2 cm and the possibility of fertility-sparing surgery on young women desirous of pregnancy. This analysis provides support for surgeons in the choice of better management, including patients with a desire for offspring and the need for sentinel node biopsy (SNB) rather than pelvic lymphadenectomy for tumors < 4 cm, and without suspicious lymph nodes' involvement on imaging. Vaccines and early diagnosis of pre-cancerous lesions are the most effective public health tool to tackle cervical cancer worldwide. [ABSTRACT FROM AUTHOR]

The purpose of this paper was to explore the immunohistochemistry (IHC) results for a cocktail of minichromosome maintenance protein 2 (MCM2) and topoisomerase IIα (TOP2A), p16INK4a and Ki-67 as biomarkers for the diagnosis of cervical intraepithelial neoplasia (CIN), improving the routine interpretation of cervical histopathology. 133 cases of CIN were collected from the archival data. All routine hematoxylin and eosin (HE)-stained slides of the subjects were re-examined independently by three senior pathologists, to provide a "consensus diagnosis". Immunohistochemistry for the three biomarkers was performed, and the results were reviewed independently of the corresponding archival diagnosis to make a "diagnosis assisted by IHC" by the original pathological practitioners. The diagnosis accordance rate of the archival original diagnosis with the "consensus diagnosis" and the "diagnosis assisted by IHC" with the "consensus diagnosis" were verified by Fisher's exact test. The results showed that raw agreement between the original HE diagnosis and the "consensus diagnosis" was 88.55%, and raw agreement between the "diagnosis assisted by IHC" and the "consensus diagnosis" was 95.78%. The latter was significantly higher than the former (Fisher's exact test, p=0.023). In conclusion, the three biomarkers had a high degree of sensitivity and specificity, and appear to be a useful and reliable diagnostic adjunct to improve the routine diagnosis, and reduce inter-observer variability in cervical biopsy specimens [ABSTRACT FROM AUTHOR]

Objectives: To establish the cytological criteria to identify the urothelial cells in cervical smears in order to avoid mistakes in the cytological diagnosis. Materials and Methods: Cervical smears from 34 post menopausal women with vesicovaginal fistulas, advanced bladder prolapse and genital erosive lichen planes (vulvar kraurosis) (Group 1) and transitional cell metaplasia of the cervix (TCM, Group 2) were stained with Papanicolaou technique. The cervical samples were taken during the routine annual examination for prevention of the uterine cancer. Results: The smears of cervix from Group 1 showed urothelial cells from the three layers of the transitional epithelium. The umbrella cells are the bigger ones with relatively large nuclei. Frequently, they are multinucleated with single or multiple nucleoli and a typical "frothy" cytoplasm (cytoplasmic vacuoles). The cells of the Group 2 showed nuclei with oval to spindled shapes, some tapered ends, less cytoplasm than squamous metaplastic cells, powdery chromatin, small nucleoli and nuclear grooves. Conclusions: The umbrella cells may be mistaken for dysplastic cells originating in low grade squamous intraepithelial lesions lesions (LSILs) due to their nuclear and cytoplasm sizes. Therefore, it is important to know the possibility of their appearance in the cervical smears, especially in post menopausal patients in order to avoid a false diagnosis of an intraepithelial lesion. It is unlikely that deeper cells of urothelium would be confused with high grade squamous intraepithelial lesion (HSIL) cells. However, their presence might be a reason of mistake in the diagnosis. TCM is an under-recognized metaplastic phenomenon of the cervix and vagina, which is a mimicker of high grade squamous intraepithelial lesion. The differential characteristic between umbrella cells, cells from TCM and the deeper urothelial cells, and LSIL and HSIL are detailed in the present paper. [ABSTRACT FROM AUTHOR]

INTRODUCTION The aim was to evaluate the association between secondhand smoke (SHS) exposure and abnormal cervical cytology among Chinese adult women. METHODS A one-to-one matched case-control study was conducted with outpatients of the First Hospital of Jilin University between October 2013 to September 2016. In all, 228 cytologic confirmed new cases of abnormal cervical cytology and the equivalent number of age and ethnic matched controls were interviewed about SHS exposure and related factors. RESULTS Although 78.3% of all the participants had been exposed to SHS (78.1% subjects vs 78.5% controls), there were no statistical significance of cervical cytological abnormalities and SHS exposure status (never, former, current exposure), exposure intensity in cigarettes per day (none, 1-9, 10-19, and >20), SHS exposure duration in years (none, 1-9, 10-19, and >20) and the Brinkman Index (BI) (none, 1-99, 100-399, >400) between the two groups. The univariate analysis results showed that there were statistical differences between subjects and controls in marital status, sexual frequency in past year, number of sexual partners, age at first intercourse, age at first delivery. The stratified Cox regression model only showed that the age at first sexual intercourse was associated with the cervical cytological abnormalities (0R=1.206, 95% CI: 1.104-1.319). CONCLUSIONS Studies on the association between SHS exposure and cervical lesions have been equivocal. In this study, the SHS exposure could not be detected as an independent risk factor of abnormal cervical cytology among Chinese adult women. [ABSTRACT FROM AUTHOR]

The aim of this paper was to evaluate the factors that predict regression of untreated CIN 2 and 3. A total of 93 patients with colposcopic persistent CIN 2 and 3 lesions after biopsy were followed for 6 months. Human papillomavirus (HPV) types were determined by polymerase chain reaction at enrolment. We analysed the biologic and demographic predictors of natural regression using univariate and multivariate methods. The overall regression rate was 52% (48 out of 93), including 58% (22 out of 38) of CIN 2 and 47% (26 out of 55) of CIN 3 lesions (P=0.31 for difference). Human papillomavirus was detected in 84% (78 out of 93) of patients. In univariate analysis, 80% (12 out of 15) of lesions without HPV regressed compared to 46% (36 out of 78) of lesions with HPV infection (P=0.016). Women without HPV and those who had a resolution of HPV had a four-fold higher chance of regression than those with persistent HPV (relative odds=3.5, 95% CI=1.4-8.6). Women with five or fewer lifetime sexual partners had higher rates of regression than women with more than five partners (P=0.003). In multivariate analysis, HPV status and number of sexual partners remained as significant independent predictors of regression. In conclusion, HPV status and number of lifetime sexual partners were strongly predictive of regression of untreated CIN 2 and 3. [ABSTRACT FROM AUTHOR]

There is evidence that diet and nutrition are modifiable risk factors for several cancers. In recent years, attention paid to micronutrients in gynecology has increased, especially regarding Human papillomavirus (HPV) infection. We performed a review of the literature up until December 2022, aiming to clarify the effects of micronutrients, minerals, and vitamins on the history of HPV infection and the development of cervical cancer. We included studies having as their primary objective the evaluation of dietary supplements, in particular calcium; zinc; iron; selenium; carotenoids; and vitamins A, B12, C, D, E, and K. Different oligo-elements and micronutrients demonstrated a potential protective role against cervical cancer by intervening in different stages of the natural history of HPV infection, development of cervical dysplasia, and invasive disease. Healthcare providers should be aware of and incorporate the literature evidence in counseling, although the low quality of evidence provided by available studies recommends further well-designed investigations to give clear indications for clinical practice. [ABSTRACT FROM AUTHOR]

Background: With HPV screening the specificity of screening positives has decreased, even with a cytological triage test. Increases in colposcopies and detection of benign or low-grade dysplasia are reported, not least in older women. These results highlight the necessity to find other triage tests in HPV screening strategies, so that women can be more accurately selected for colposcopy, thus minimizing the clinically irrelevant findings. Methods: The study included 55- to 59-year-old women who exited the screening with normal cytology, but later in a follow-up test were positive for the HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 and had a cervical cone biopsy done. To model a screening situation with hrHPV-positive women, three different triage strategies, namely, cytology, genotyping and methylation, were performed. The study considered the effect of direct referral to colposcopy for HPV genotypes 16, 18, 31, 33, 45, 52 and 58, and methylation for FAM19A4 and hsa-mir124-2 and/or any form of abnormal cytology. Results: Seven out of 49 women aged 55–59 years with hrHPV had a cone biopsy with high-grade squamous intraepithelial lesion. No triage method found all cases, and when comparing positive and negative predictive value and false negative rate, cytology showed better results than genotyping and methylation. Conclusion: This study does not support a switch in triage strategies from cytology to hrHPV genotyping and methylation for women above 55 years of age yet, but demonstrates the need for more evidence on molecular triage strategies. [ABSTRACT FROM AUTHOR]

Several hundred million people are infected with genital genotypes of the human papillomavirus (HPV) annually in the world. The infections transmitted mainly through sexual routes are usually asymptomatic, but can lead to the development of cervical, vulvar, vaginal, anal, and penile cancers, some head and neck cancers, and genital warts (condylomas). The fraction HPV-related cancers ranges from nearly 100% in the case of cervical cancer to several/over a dozen percent in the case of other cancers and diseases. There are no effective drugs against HPV, but prophylactic HPV vaccines are available free of charge in immunization programmes in many countries around the world. In Poland, HPV vaccinations have so far been executed out of pocket or in freeof- charge, local-governmental prevention programmes, but the vaccination coverage of the target population does not exceed 10%. In November 2021, one of the vaccines became available with a 50% reimbursement, work is underway to reimburse the next ones, and the National Oncology Strategy assumes the implementation of the HPV immunization programmes and vaccination of 60% of the teenage population by 2028. Three prophylactic HPV vaccines are registered. All of them are safe and their effectiveness in the prevention of diseases caused by vaccine genotypes is almost 100%, provided that full post-vaccination immunity is obtained before contact with the virus. Girls aged 11--13 years are the priority target cohort for HPV vaccination in Poland. The implementation of routine, free-of-charge HPV immunization in the Preventive Immunization Programme (PIP) for all adolescents should be pursued. Persons over the age of 13 years may also benefit from HPV vaccination and should be vaccinated according to product specifications. In addition to free access under the PIP, the key element for the success of the implementation of HPV vaccinations in Poland will be the education of medical personnel and parents of adolescents to be vaccinated. [ABSTRACT FROM AUTHOR]

Introduction. Cervico-isthmic insufficiency is one of the causes of second-trimester abortion and premature birth. This term is used to denote a pathological condition characterized by shortening of the cervix (shorter than 25 mm), dilation of the cervical internal opening (“funneling” - from the English term “funnel”, which refers to the “funnel” shape of a tube wide to one end and narrow to the other) or the entire uterine cervix, apparently spontaneous, initially without painful uterine contractions, followed by abortion or premature birth. In the past, the diagnosis was made either by “testing” the uterine cervix outside of pregnancy (if it was permeable directly to Hegar no. 8), or after the patient had lost some pregnancies after the first trimester, without contractions, in the absence of other apparent causes. Repeated pregnancy losses in the second trimester or premature births without contractions or bleeding eventually led to the diagnosis, but unfortunately, often too late. Ultrasound for cervical evaluation - even though controversies still exist - has made tremendous progress in diagnosis by allowing cervical length assessment and the assessment of internal orifice status, as well as tracking the evolution of these parameters in dynamics. Once the diagnosis is established, the problem of therapeutic intervention is raised. As for the attitude to be followed, there is no consensus, especially since new methods or new variants of older methods have emerged, which generates a continuous evaluation and reevaluation process. The classic triad bed rest, litic treatment, cerclage is currently being challenged by followers of some newer methods. Objective. The aim of this paper is to formulate a therapeutic algorithm related to the problem of cervico-isthmic insufficiency. Method. The method used is the meta-analysis of the data from literature and of the ones from our own experience and the statistical processing. Discussions. Systematizing the attitude to be followed, data on the bed rest and limitation of activity, drug treatment (lithic, progesterone, antibiotic, use of indomethacin), use of the pessary or cerclage (alone or combined) were analyzed. Conclusions. If in the prevention of abortion and premature birth, cerclage has a clear advantage, the cervical pessary is under discussion (despite controversial data) to prevent premature births. Although initially blamed, the association of cervical cerclage with cervical pessary seems to offer some advantages; however, this will be considered in larger (significant) studies. In terms of drug treatment, progesterone appears to be advantageous, and indirectly, the use of lithic or antibiotic therapy for associated pathology or complications. Lifestyle changes and bed rest do not seem to be adequately assessed through welldesigned studies, although it is considered, regarding the bed rest, that risks (e.g., venous thrombosis) outweigh the potential benefits. [ABSTRACT FROM AUTHOR]

We report here identification and validation of the first papillomavirus encoded microRNAs expressed in human cervical lesions and cell lines. We established small RNA libraries from ten human papillomavirus associated cervical lesions including cancer and two human papillomavirus harboring cell lines. These libraries were sequenced using SOLiD 4 technology. We used the sequencing data to predict putative viral microRNAs and discovered nine putative papillomavirus encoded microRNAs. Validation was performed for five candidates, four of which were successfully validated by qPCR from cervical tissue samples and cell lines: two were encoded by HPV 16, one by HPV 38 and one by HPV 68. The expression of HPV 16 microRNAs was further confirmed by in situ hybridization, and colocalization with p16INK4A was established. Prediction of cellular target genes of HPV 16 encoded microRNAs suggests that they may play a role in cell cycle, immune functions, cell adhesion and migration, development, and cancer. Two putative viral target sites for the two validated HPV 16 miRNAs were mapped to the E5 gene, one in the E1 gene, two in the L1 gene and one in the LCR region. This is the first report to show that papillomaviruses encode their own microRNA species. Importantly, microRNAs were found in libraries established from human cervical disease and carcinoma cell lines, and their expression was confirmed in additional tissue samples. To our knowledge, this is also the first paper to use in situ hybridization to show the expression of a viral microRNA in human tissue. [ABSTRACT FROM AUTHOR]

The localization of cervical lymph nodes is extremely important in practice for the positive and differential diagnosis as well as the staging of cervical lymphadenopathies. Ultrasonography represents the first line imaging method in the diagnosis of cervical lymphadenopathies due to its excellent resolution and high diagnosis accuracy. The present paper aims to illustrate the ultrasonographic identification of the anatomical landmarks used for the definition of cervical lymphatic spaces. The application of standardized views allows a delineation of clear anatomical landmarks and an accurate localization of the cervical lymph nodes. [ABSTRACT FROM AUTHOR]

A conference paper about biomarkers of cervicovaginal inflammation for the assessment of microbicide safety is presented. It examines the mucosal immunity in the female genital tract and the cellular and molecular mechanisms of mucosal inflammation. It discusses the biomarkers for preclinical evaluation of microbicide safety.

Objectives: Mycoplasma genitalium has been associated with cervicitis, endometritis, and tubal factor infertility. Because the ability of this bacterium to ascend and infect the fallopian tube remains undefined, we performed an investigation to determine the prevalence of M genitalium in fallopian tube, endometrial, and cervical specimens from women laparoscopically diagnosed with acute salpingitis in Nairobi, Kenya.Methods: Women presenting with pelvic inflammatory disease were laparoscopically diagnosed with salpingitis. Infection with M genitalium in genital specimens was determined by polymerase chain reaction (PCR).Results: Of 123 subjects with acute salpingitis, M genitalium was detected by PCR in the cervix and/or endometrium in nine (7%) participants, and in a single fallopian tube specimen. In addition, those infected with M genitalium were more often HIV infected than women not infected by M genitalium (seven of nine (78%) v 42 of 114 (37%), p<0.03).Conclusions: M genitalium is able to ascend into the fallopian tube, but its association with tubal pathology requires further investigation. [ABSTRACT FROM AUTHOR]

Cervical cancer is the fourth most common cancer and fourth leading cause of cancer death among women worldwide. In low Human Development Index settings, it ranks second. Screening and surveillance involve the cytology-based Papanicolaou (Pap) test and testing for high-risk human papillomavirus (hrHPV). The Pap test has low sensitivity to detect precursor lesions, while a single hrHPV test cannot distinguish a persistent infection from one that the immune system will naturally clear. Furthermore, among women who are hrHPV-positive and progress to high-grade cervical lesions, testing cannot identify the ~20% who would progress to cancer if not treated. Thus, reliable detection and treatment of cancers and precancers requires routine screening followed by frequent surveillance among those with past abnormal or positive results. The consequence is overtreatment, with its associated risks and complications, in screened populations and an increased risk of cancer in under-screened populations. Methods to improve cervical cancer risk assessment, particularly assays to predict regression of precursor lesions or clearance of hrHPV infection, would benefit both populations. Here we show that women who have lower risk results on follow-up testing relative to index testing have evidence of enhanced T cell clonal expansion in the index cervical cytology sample compared to women who persist with higher risk results from index to follow-up. We further show that a machine learning classifier based on the index sample T cells predicts this transition to lower risk with 95% accuracy (19/20) by leave-one-out cross-validation. Using T cell receptor deep sequencing and machine learning, we identified a biophysicochemical motif in the complementarity-determining region 3 of T cell receptor β chains whose presence predicts this transition. While these results must still be tested on an independent cohort in a prospective study, they suggest that this approach could improve cervical cancer screening by helping distinguish women likely to spontaneously regress from those at elevated risk of progression to cancer. The advancement of such a strategy could reduce surveillance frequency and overtreatment in screened populations and improve the delivery of screening to under-screened populations. [ABSTRACT FROM AUTHOR]

Background: Previous studies have found that the microenvironment of cervical cancer (CESC) affects the progression and treatment of this disease. Thus, we constructed a multigene model to assess the survival of patients with cervical cancer. Methods: We scored 307 CESC samples from The Cancer Genome Atlas (TCGA) and divided them into high and low matrix and immune scores using the ESTIMATE algorithm for differential gene analysis. Cervical cancer patients were randomly divided into a training group, testing group and combined group. The multigene signature prognostic model was constructed by Cox analyses. Multivariate Cox analysis was applied to evaluate the significance of the multigene signature for cervical cancer prognosis. Prognosis was assessed by Kaplan–Meier curves comparing the different groups, and the accuracy of the prognostic model was analyzed by receiver operating characteristic-area under the curve (ROC-AUC) analysis and calibration curve. The Tumor Immune Estimation Resource (TIMER) database was used to analyze the relationship between the multigene signature and immune cell infiltration. Results: We obtained 420 differentially expressed genes in the tumor microenvironment from 307 patients with cervical cancer. A three-gene signature (SLAMF1, CD27, SELL) model related to the tumor microenvironment was constructed to assess patient survival. Kaplan–Meier analysis showed that patients with high risk scores had a poor prognosis. The ROC-AUC value indicated that the model was an accurate predictor of cervical cancer prognosis. Multivariate cox analysis showed the three-gene signature to be an independent risk factor for the prognosis of cervical cancer. A nomogram combining the three-gene signature and clinical features was constructed, and calibration plots showed that the nomogram resulted in an accurate prognosis for patients. The three-gene signature was associated with T stage, M stage and degree of immune infiltration in patients with cervical cancer. Conclusions: This research suggests that the developed three-gene signature may be applied as a biomarker to predict the prognosis of and personalized therapy for CESC. [ABSTRACT FROM AUTHOR]

Background: Systematic pelvic lymphadenectomy or whole pelvic irradiation is recommended for the patients with stage IB1 cervical cancer. However, the precise pattern of lymphatic tumor spread in cervical cancer is unknown. In the present study we evaluated the distribution of nodal metastases in stage IB1 cervical cancer to explore the possibilities for tailoring cancer treatment.Methods: A total of 289 patients with cervical cancer of stage IB1, according to FIGO 2009, were retrospectively analyzed. All patients underwent laparoscopic radical hysterectomy (Querleu and Morrow type C2) and systematic pelvic lymphadenectomy with or without para-aortic lymphadenectomy (level 2 or level 3 according to Querleu and Morrow) from October 2014 to December 2017. Lymph nodes removed from 7 well-defined anatomical locations as well as other tissues were examined histopathologically, and typed, graded, and staged according to the WHO/IARC classification.Results: Totally 8314 lymph nodes were analyzed with the average number of 31.88 ± 10.34 (Mean ± SD) lymph nodes per patient. Nodal metastases were present in 44 patients (15.22%). The incidence of lymphatic spread to different anatomic sites ranged from 0% (presacral) to 30.92% (obturator nodes). Tumor size above 2 cm, histologically proven lymphovascular space involvement (LVSI) and parametrial invasion were shown to be significantly correlated with the higher risk of lymphatic metastasis, while obesity (BMI ≥ 25) was independently negatively associated with lymphatic metastases.Conclusions: The incidence of lymph node metastasis in patients with stage IB1 cervical cancer is low but prognostically relevant. Individual treatment could be considered for the selected low-risk patients who have smaller tumors and obesity and lack of the parametrial invasion or LVSI. [ABSTRACT FROM AUTHOR]

The cervix is responsible for maintaining pregnancy, and its timely remodeling is essential for the proper delivery of a baby. Cervical insufficiency, or "weakness", may lead to preterm birth, which causes infant morbidities and mortalities worldwide. We used a mouse model of pregnancy and term labor, to examine the cervical structure by histology (Masson Trichome and Picrosirius Red staining), immunohistochemistry (Hyaluronic Acid Binding Protein/HABP), and ex-vivo MRI (T2-weighted and diffusion tensor imaging), focusing on two regions of the cervix (i.e., endocervix and ectocervix). Our results show that mouse endocervix has a higher proportion of smooth muscle cells and collagen fibers per area, with more compact tissue structure, than the ectocervix. With advanced gestation, endocervical changes, indicative of impending delivery, are manifested in fewer smooth muscle cells, expansion of the extracellular space, and lower presence of collagen fibers. MRI detected three distinctive zones in pregnant mouse endocervix: (1) inner collagenous layer, (2) middle circular muscular layer, and (3) outer longitudinal muscular layer. Diffusion MRI images detected changes in tissue organization as gestation progressed suggesting the potential application of this technique to non-invasively monitor cervical changes that precede the onset of labor in women at risk for preterm delivery. [ABSTRACT FROM AUTHOR]

Background: To improve the efficiency of early diagnosis systems for cervical cancer, the use of cellular and viral markers for identifying precancerous lesions with a greater probability to progress to cancer has been proposed. Several cellular proteins and markers of oxidative DNA damage have been suggested as possible biomarkers of cervical carcinogenesis; however, they have not been evaluated together. In this study, we analyzed the expression of the cellular markers p16INK4a, Ki-67, CyclinE1, TOP2A/MCM2, and telomerase, as well as the DNA oxidative damage markers ROS and 8-OHdG. The analyses were performed in liquid-based cervical cytology samples or biopsies with premalignant lesions or cervical cancer diagnosis, with the purpose of selecting a panel of biomarkers that allow the identification of precursor lesions with greater risk of progression to cervical cancer.Methods: We analyzed 1485 liquid-based cytology samples, including 239 non-squamous intraepithelial lesions (NSIL), 901 low-grade squamous intraepithelial lesions (LSIL), 54 high-grade squamous intraepithelial lesions (HSIL), and 291 cervical cancers (CC). The biomarkers were analyzed by immunocytochemistry and Human Papilloma Virus (HPV) genotyping with the INNO-LiPA genotyping Extra kit.Results: We found that all tested cellular biomarkers were overexpressed in samples with high risk-HPV infection, and the expression levels increased with the severity of the lesion. TOP2A/MCM2 was the best biomarker for discriminating between LSIL and HSIL, followed by p16INK4a and cyclinE1. Statistical analysis showed that TOP2A/MCM2 provided the largest explanation of HSIL and CC cases (93.8%), followed by p16INK4a (91%), cyclin E1 (91%), Ki-67 (89.3%), and telomerase (88.9%).Conclusions: We propose that the detection of TOP2A/MCM2, p16INK4a and cyclin E1 expression levels is useful as a panel of biomarkers that allow identification of cervical lesions with a higher risk for progression to CC with high sensitivity and precision; this can be done inexpensively, in a single and non-invasive liquid-based cytology sample. [ABSTRACT FROM AUTHOR]

Background: Colposcopy diagnosis and directed biopsy are the key components in cervical cancer screening programs. However, their performance is limited by the requirement for experienced colposcopists. This study aimed to develop and validate a Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) for grading colposcopic impressions and guiding biopsies.Methods: Anonymized digital records of 19,435 patients were obtained from six hospitals across China. These records included colposcopic images, clinical information, and pathological results (gold standard). The data were randomly assigned (7:1:2) to a training and a tuning set for developing CAIADS and to a validation set for evaluating performance.Results: The agreement between CAIADS-graded colposcopic impressions and pathology findings was higher than that of colposcopies interpreted by colposcopists (82.2% versus 65.9%, kappa 0.750 versus 0.516, p < 0.001). For detecting pathological high-grade squamous intraepithelial lesion or worse (HSIL+), CAIADS showed higher sensitivity than the use of colposcopies interpreted by colposcopists at either biopsy threshold (low-grade or worse 90.5%, 95% CI 88.9-91.4% versus 83.5%, 81.5-85.3%; high-grade or worse 71.9%, 69.5-74.2% versus 60.4%, 57.9-62.9%; all p < 0.001), whereas the specificities were similar (low-grade or worse 51.8%, 49.8-53.8% versus 52.0%, 50.0-54.1%; high-grade or worse 93.9%, 92.9-94.9% versus 94.9%, 93.9-95.7%; all p > 0.05). The CAIADS also demonstrated a superior ability in predicting biopsy sites, with a median mean-intersection-over-union (mIoU) of 0.758.Conclusions: The CAIADS has potential in assisting beginners and for improving the diagnostic quality of colposcopy and biopsy in the detection of cervical precancer/cancer. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is among the most common preventable cancers with the highest morbidity and mortality. The World Health Organization (WHO) recommends visual inspection of the cervix with acetic acid (VIA) as cervical cancer screening strategy in resource-poor settings. However, there are barriers to the sustainability of VIA programs including declining providers' VIA competence without mentorship and quality assurances and challenges of integration into primary healthcare. This study seeks to evaluate the impact of smartphone-based strategies in improving reliability, reproducibility, and quality of VIA in humanitarian settings.Methods and Findings: We implemented smartphone-based VIA that included standard VIA training, adapted refresher, and 6-month mHealth mentorship, sequentially, in the rural Shiselweni region of Eswatini. A remote expert reviewer provided diagnostic and management feedback on patients' cervical images, which were reviewed weekly by nurses. Program's outcomes, VIA image agreement rates, and Kappa statistic were compared before, during, and after training. From September 1, 2016 to December 31, 2018, 4,247 patients underwent screening; 247 were reviewed weekly by a VIA diagnostic expert. Of the 247, 128 (49%) were HIV-positive; mean age was 30.80 years (standard deviation [SD]: 7.74 years). Initial VIA positivity of 16% (436/2,637) after standard training gradually increased to 25.1% (293/1,168), dropped to an average of 9.7% (143/1,469) with a lowest of 7% (20/284) after refresher in 2017 (p = 0.001), increased again to an average of 9.6% (240/2,488) with a highest of 17% (17/100) before the start of mentorship, and dropped to an average of 8.3% (134/1,610) in 2018 with an average of 6.3% (37/591) after the start of mentorship (p = 0.019). Overall, 88% were eligible for and 68% received cryotherapy the same day: 10 cases were clinically suspicious for cancer; however, only 5 of those cases were confirmed using punch biopsy. Agreement rates with the expert reviewer for positive and negative cases were 100% (95% confidence interval [CI]: 79.4% to 100%) and 95.7% (95% CI: 92.2% to 97.9%), respectively, with negative predictive value (NPV) (100%), positive predictive value (PPV) (63.5%), and area under the curve of receiver operating characteristics (AUC ROC) (0.978). Kappa statistic was 0.74 (95% CI; 0.58 to 0.89); 0.64 and 0.79 at 3 and 6 months, respectively. In logistic regression, HIV and age were associated with VIA positivity (adjusted Odds Ratio [aOR]: 3.53, 95% CI: 1.10 to 11.29; p = 0.033 and aOR: 1.06, 95% CI: 1.0004 to 1.13; p = 0.048, respectively). We were unable to incorporate a control arm due to logistical constraints in routine humanitarian settings.Conclusions: Our findings suggest that smartphone mentorship provided experiential learning to improve nurses' competencies and VIA reliability and reproducibility, reduced false positive, and introduced peer-to-peer education and quality control services. Local collaboration; extending services to remote populations; decreasing unnecessary burden to screened women, providers, and tertiary centers; and capacity building through low-tech high-yield screening are promising strategies for scale-up of VIA programs. [ABSTRACT FROM AUTHOR]

Background: In South Africa, breast cancer is the most commonly diagnosed cancer and cervical cancer the leading cause of cancer mortality. Most cancers are diagnosed at a late-stage and following symptomatic presentation. The overall purpose of the study was to inform interventions aimed at improving timely diagnosis of breast and cervical cancer.Methods: In-depth interviews were conducted with women with potential breast or cervical cancer symptoms from urban and rural South Africa. Participants were recruited from a community-based cross-sectional study on breast and cervical cancer awareness. Data were analysed using a thematic analysis approach.Results: Eighteen women were interviewed (10 urban, 8 rural): the median age was 34.5 years (range 22-58). Most were unemployed, and five were HIV positive. Themes included impact and attribution of bodily changes; influence of social networks and health messaging in help-seeking; management of symptoms and help-seeking barriers. Breast changes were often attributed to manual activities or possible cancer. Women were often unsure how to interpret vaginal symptoms, attributing them to HIV, hormonal contraceptives, or partner infidelity. Concerns about cancer were based on health information from the radio, social networks, or from primary care providers. Prompt care seeking was triggered by impact of symptoms on personal lives. Rural women, especially with possible symptoms of cervical cancer, experienced challenges during help-seeking including judgmental attitudes of clinic staff. Most participants were skeptical of traditional medicine.Conclusions: This is the first study exploring interpretation of possible breast and cervical cancer symptoms at a community level in South Africa. The process of interpreting bodily changes, symptom attribution and help-seeking is complex and influenced by women's everyday life experiences. Timely diagnosis interventions should not only include cancer symptom awareness but also address individual, structural and health systems related barriers to care. [ABSTRACT FROM AUTHOR]

Cervical cancer is a malignant tumour that occurs in the cervix and is classified into two histological types, adenocarcinoma and squamous cell carcinoma (SCC); SCC is more common and accounts for 70% of all cases. In 2018 there were ~569,000 new cases of cervical cancer diagnosed worldwide and ~311,000 deaths were attributed to cervical cancer. Of these, between 84 and 90% occurred in low- and middle-income countries (LMICs) such as South Africa, India, China and Brazil. The most common cause of cervical cancer is persistent infection caused by the sexually transmitted human papilloma virus. Other factors that contribute to the incidence of cervical cancer include geography, traditional practices and beliefs, the screening levels, socioeconomic status, healthcare access, public awareness, use of oral contraceptives, smoking and co-infection with HIV. An estimated 11 million women from LMICs will be diagnosed with cervical cancer in the next 10–20 years. The aim of this review was to explore various types of genetic and epigenetic factors that influence the development, progression or suppression of cervical cancer. [ABSTRACT FROM AUTHOR]

Necrotizing fasciitis is a rapidly progressive soft tissue infection that can cause local tissue destruction, necrosis, and life threatening severe sepsis. Necrotizing fasciitis in the head and neck region caused by an extravasation injury is rare. This paper reports a patient with necrotizing fasciitis of the cervical region caused by an extravasation injury which required an early surgical debridement. [ABSTRACT FROM AUTHOR]

There is a lack of knowledge on the histologic outcomes of loop electrosurgical excision procedure (LEEP) biopsies in the diagnosis, treatment, and prevention of cervical cancer in Zambia. This study determined the outcomes of LEEP biopsies and associated factors at a tertiary hospital. We conducted a retrospective chart review of patients evaluated at a tertiary hospital cervical cancer screening centre. From the database, we identified patients who underwent LEEP between January 2015 and June 2018. We extracted demographic data, HIV data, and LEEP biopsy results. A P value less than 0.05 was considered statistically significant. 137 charts were identified, and 114 were included in the final analysis. 23 were excluded for missing histology. The mean age of participants was 36.3 ± 9.6. Histology outcomes revealed that 37% had cervicitis, while CIN 1, 2, and 3 contributed to 27%, 14%, and 3%, respectively. Squamous cell cancer was present in 8% (age groups 35–49) and was three times higher (13%) in HIV-positive compared to HIV-negative participants (3.8%). Normal histology accounted for 11%. Increasing age (P = 0.029), less than tertiary education (P = 0.0011), and being married (P = 0.017) increased the chances of having cancer in the chi-square analysis, while single women had lower odds of having CIN 1 (OR = 0.012) in the multinomial logistic regression. There is a need for increased cervical cancer screening and training in precancer treatment and holistic consideration of other factors like age in addition to the positive VIA test in advising patients on treatment options. [ABSTRACT FROM AUTHOR]

The determination of factors associated with progression of cervical cancer is important, both for a recurrence risk assessment and for determining optimal treatment tactics. Previously, we showed the prognostic value of different types of tumor microvessels (MVs) in gastric and breast cancer. The object of this research was to study the morphology and clinical significance of different tumor microvessels in early cervical cancer. A total of 65 archived paraffin blocks of patients with I-IIA stages of squamous cervical cancer were investigated. Samples were stained with Mayer hematoxylin and immunohistochemically using antibodies to CD34, podoplanin, HIF-1a, and Snail. The eight types of tumor MVs differed in morphology were identified. It was established that only the dilated capillaries (DСs) with weak expression of CD34, the contact type DCs, the capillaries in tumor solid component, and the lymphatic vessels in the lymphoid and polymorphic cell infiltrates of tumor stroma are associated with clinical and pathological characteristics of early cervical cancer. Preliminary results also suggest that a combination of fragmentation in tumor solid component and the contact type DCs may predict a recurrence of early cervical cancer. Given the small number of cervical cancer recurrences, the predictive significance of the described markers requires a more thorough examination. [ABSTRACT FROM AUTHOR]

Colposcopy is widely used to detect cervical cancers, but experienced physicians who are needed for an accurate diagnosis are lacking in developing countries. Artificial intelligence (AI) has been recently used in computer-aided diagnosis showing remarkable promise. In this study, we developed and validated deep learning models to automatically classify cervical neoplasms on colposcopic photographs. Pre-trained convolutional neural networks were fine-tuned for two grading systems: the cervical intraepithelial neoplasia (CIN) system and the lower anogenital squamous terminology (LAST) system. The multi-class classification accuracies of the networks for the CIN system in the test dataset were 48.6 ± 1.3% by Inception-Resnet-v2 and 51.7 ± 5.2% by Resnet-152. The accuracies for the LAST system were 71.8 ± 1.8% and 74.7 ± 1.8%, respectively. The area under the curve (AUC) for discriminating high-risk lesions from low-risk lesions by Resnet-152 was 0.781 ± 0.020 for the CIN system and 0.708 ± 0.024 for the LAST system. The lesions requiring biopsy were also detected efficiently (AUC, 0.947 ± 0.030 by Resnet-152), and presented meaningfully on attention maps. These results may indicate the potential of the application of AI for automated reading of colposcopic photographs. [ABSTRACT FROM AUTHOR]

The role of pathology in improving cancer in resource‐limited countries is essential, yet many barriers exist. FNA is a rapid, low‐cost and efficient method for diagnosing cancer, planning treatment, and building a cancer registry. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer incidence is high among women living with HIV due to high-risk HPV persistence in the cervix. In low-income countries, cervical cancer screening is based on visual inspection with acetic acid. Implementing human papilloma virus (HPV) screening through self-sampling could increase women's participation and screening performance. Our study aims to assess the preintervention acceptability of HPV screening among HIV-infected women in Abidjan, Côte d'Ivoire.Methods: Applying the Health Belief Model theoretical framework, we collected qualitative data through in-depth interviews with 21 HIV-infected women treated in an HIV-dedicated clinic. Maximum variation sampling was used to achieve a diverse sample of women in terms of level of health literacy. Interviews were recorded and transcribed with the participants' consent. Data analysis was performed using NVivo 12.Results: Screening acceptability relies on cervical cancer representations among women. Barriers were the fear of diagnosis and the associated stigma disregard for HIV-associated health conditions, poor knowledge of screening and insufficient resources for treatment. Fees removal, higher levels of knowledge about cervical cancer and of the role of HIV status in cancer were found to facilitate screening. Healthcare providers are obstacle removers by their trusting relationship with women and help navigating through the healthcare system. Self-confidence in self-sampling is low.Conclusions: Free access to cervical screening, communication strategies increasing cervical cancer knowledge and healthcare provider involvement will foster HPV screening. Knowledge gathered through this research is crucial for designing adequate HPV-based screening interventions for women living with HIV in this setting. [ABSTRACT FROM AUTHOR]

Background: HIV-associated cellular immune dysfunction has been linked to higher risk of cervical dysplasia and cancer in HIV infected women. We sought to understand the relationship between HIV and development of epithelial cell abnormalities (ECA) at follow-up in women with prior normal cervical cytology (NCC). Methods: Retrospective cohort analysis of women who received a Pap test at the Operation Stop Cervical Cancer Unit in Jos, Nigeria over a 10-year period (2006–2016). We analyzed the data of women with NCC at first Pap who had at least one follow-up cytology result for time-to-detection of ECA. We determined follow-up time in years from date of first NCC to date of first ECA report or date of last NCC follow up report with censoring at last follow-up date or December 31st, 2016 whichever came first. The primary outcome was development of any ECA as defined by the Bethesda 2001 reporting system. We identified demographic and clinical factors associated with incident ECA using multivariable Cox regression. Results: A total of 1599 women were eligible for this analysis. Overall, 3.7% (57/1556) of women reported being HIV infected. The median age at first Pap was 39 years (IQR; 33–45). The HIV infected women were younger (36.3 ± 8.1) compared to those uninfected (39.3 ± 6.6), p = 0.005. After an accrued follow-up time of 3809 person-years (PYs), 243 women (15%) had an ECA with an event rate of 6.38 per 100 PYs. Women ≥35 years at first Pap were more likely to have an ECA compared to those < 35 years (7.5 per 100 PYs vs 3.8 per 100 PYs, HR = 1.96; 95% CI: 1.4, 2.8). HIV status was not significantly associated with developing ECA in either unadjusted (7.4 per 100 PYs vs 6.4 per 100 PYs, HR = 1.17; 95% CI: 0.53, 2.3) or adjusted analyses (aHR = 1.78; 95% CI: 0.87, 3.65). Conclusion: Women living with HIV and on successful antiretroviral treatment may not have a differential hazard in the development of ECA during follow up after a prior normal Pap. Offering a repeat CCS to women who are 35 years or older irrespective of HIV status is likely an effective strategy in resource limited settings. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis and continuous monitoring are necessary for an efficient management of cervical cancers (CC). Liquid biopsy, such as detecting circulating tumor DNA (ctDNA) from blood, is a simple, non-invasive method for testing and monitoring cancer markers. However, tumor-specific alterations in ctDNA have not been extensively investigated or compared to other circulating biomarkers in the diagnosis and monitoring of the CC. Therfore, Next-generation sequencing (NGS) analysis with blood samples can be a new approach for highly accurate diagnosis and monitoring of the CC.Method: Using a bioinformatics approach, we designed a panel of 24 genes associated with CC to detect and characterize patterns of somatic single-nucleotide variations, indels, and copy number variations. Our NGS CC panel covers most of the genes in The Cancer Genome Atlas (TCGA) as well as additional cancer driver and tumor suppressor genes. We profiled the variants in ctDNA from 24 CC patients who were being treated with systemic chemotherapy and local radiotherapy at the Jeonbuk National University Hospital, Korea.Result: Eighteen out of 24 genes in our NGS CC panel had mutations across the 24 CC patients, including somatic alterations of mutated genes (ZFHX3-83%, KMT2C-79%, KMT2D-79%, NSD1-67%, ATM-38% and RNF213-27%). We demonstrated that the RNF213 mutation could be used potentially used as a monitoring marker for response to chemo- and radiotherapy.Conclusion: We developed our NGS CC panel and demostrated that our NGS panel can be useful for the diagnosis and monitoring of the CC, since the panel detected the common somatic variations in CC patients and we observed how these genetic variations change according to the treatment pattern of the patient. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is the second most common cancer in Ethiopia next to breast cancer. Despite the high burden of the disease and availability of free screening services in Ethiopia, uptake is still trivial. This study aims to identify factors associated with cervical cancer screening uptake, VIA (visual inspection with acetic acid) positivity and its predictors among women attending cervical cancer screening service in Addis Ababa, Ethiopia.Methods: Concurrent mixed study approach of qualitative interview (n = 15) and cross-sectional study among 844 screened women was conducted from February to July 2018. A multistage sampling technique was employed to recruit survey participants from the selected health facilities while the key informants for an in-depth interview were selected purposively. Descriptive statistics were used to summarize the quantitative data and multivariable logistic regression was employed to explore factors associated with VIA positivity of the cervix among screened women. Qualitative data were analyzed using thematic analysis approach.Results: The VIA positivity of the cervix was 10.3%. Mean age of study participants was 35.74 ± 7.6 years and women in the age group of ≥45 years were about > 8 times more likely to have VIA test positive result compared to younger women (≤24 years). Being single (AOR = 3.2, 95%CI: 1.4-7.31), widowed (AOR = 18.6, 95%CI: 3.8-91.2), initiating sexual intercourse early (< 16 years) (AOR = 2.72; 95%CI: 1.65-4.49), and having two or more lifetime sexual partners (AOR = 4.9; 95% CI: 1.31-8.75) were also found to be predictors of being VIA positive. Lack of awareness, inaccessibility of the screening service, cultural beliefs and negative perception towards cancer were found to be the major reasons for low uptake of cervical cancer screening.Conclusion: The VIA positivity among screened women in Addis Ababa was found to be moderately low compared to reports in other parts of Ethiopia. Having multiple sexual partners, being older age and initiation of sexual intercourse at an early age were associated with VIA positivity of the cervix. Thus, concerted efforts must be taken to increase accessibility of screening services and improve awareness regarding cervical cancer screening. [ABSTRACT FROM AUTHOR]

Background: For the first time, we present regional-level cancer incidence and world-standardized mortality rates for cancers for Martinique, Guadeloupe and French Guiana.Methods: For Martinique, Guadeloupe and French Guiana, incidence data come from population-based cancer registries, and cover the periods 2007-2014, 2008-2014 and 2010-2014 respectively. Standardized incidence and mortality rates were calculated using the world population.Results: In the 3 regions, all cancers combined represent 3567 new cases per year, of which 39.8% occur in women, and 1517 deaths per year (43.4% in women). Guadeloupe and Martinique present similar world-standardized incidence rates. Among gynaecological cancers, breast cancer, the second most common cancer type in the 3 regions, has an incidence rate 35 to 46% lower than in mainland France. On the other hand, cervical cancer has a higher incidence rate, particularly in French Guiana. For both endometrial cancer and ovarian cancer, no significant differences in incidence rates are found compared to mainland France. Regarding mortality, world-standardized mortality rates are similar between Guadeloupe and Martinique, and higher than in French Guiana. This situation compares favourably with mainland France (all cancers). Among gynaecological cancers, the mortality rate is lower for breast cancer in all regions compared to mainland France, and also lower for ovarian cancer in Martinique and Guadeloupe, but higher (albeit non-significantly) in French Guiana.Conclusion: The ethno-geographic and socio-demographic characteristics in this population of mainly Afro-Caribbean origin could partially explain these disparities. Major disparities exist for certain cancer sites: excess incidence and excess mortality for cervical cancer; lower, but increasing incidence of breast cancer. [ABSTRACT FROM AUTHOR]

Tumor-related leukocytosis (TRL) is correlated with poor survival in various types of cancers, but the microenvironment of TRL-associated human tumors has not been fully elucidated. Here, we aimed to characterize the immune microenvironment of cancer patients with TRL. The transcriptional signatures of tumor tissues obtained from cervical cancer patients with (TRLpos) and without TRL (TRLneg) were compared. As a surrogate for TRL diagnosis, a leukocytosis signature (LS) score was derived using genes differentially expressed between TRLpos and TRLneg tumors. The immunological profiles of patients in the TCGA database with high (LShigh) or low LS scores were compared. TRLpos tumors were transcriptionally distinct from TRLneg tumors, exhibiting up-regulation of radioresistance and down-regulation of adaptive immune response-related genes. In the TCGA cervical cancer cohort (n = 303), patients with high LS had inferior survival rates compared to those with low LS (P = 0.023). LShigh tumors were enriched in radioresistance, wound healing, and myeloid-derived suppressor cell (MDSC) signatures and had a higher infiltration of M2 macrophages and a lower infiltration of M1 macrophages and lymphocytes. LShigh tumors also expressed higher levels of CXCR2 chemokines, CSF2, and CSF3. In the pan-cancer cohort (n = 9984), LShigh tumors also exhibited poor survival, signatures of a suppressive immune microenvironment, and higher expression of CXCR2 chemokines. Our data provide evidence for a suppressive immune microenvironment in patients with TRL and suggest promising targets, such as the CXCR2 axis, for its therapeutic intervention. [ABSTRACT FROM AUTHOR]

Purpose: Cancer of the cervix is the second most common cancer among women worldwide. Despite it is a serious public health problem in Sub-Saharan African countries including Ethiopia, formation on predictor of the precancerous cervical lesion is not well documented, particularly in the study area. This study aimed to identify the predictors of precancerous cervical lesions among women screened for cervical cancer in Bahir Dar town, North West Ethiopia, 2018/19. Patient and Methods: Institution-based unmatched case–control study was conducted in selected health facilities in Bahir Dar town from November 15, 2018, to January 16, 2019. Data were collected from 102 cases and 305 controls using an interviewer-administered structured questionnaire and entered into Epi Data version 3.1, then export to SPSS version 23 for analysis. Variables with P-value ≤ 0.2 in the bivariate analysis were included in the multivariate logistic regression model. Odds ratio with 95% confidence interval was used to identify the predictors of precancerous cervical lesions. Results: Women who initiated sexual intercourse before the age of 18 years (AOR = 1.68, 95% CI: 1.015– 2.804), history of sexually transmitted infection (AOR =1.74, 95% CI: 1.087– 2.790) and two or more lifetime sexual partners (AOR=1.733, 95% CI: 1.069– 2.810) were predictors for a precancerous cervical lesions. Conclusion: This study confirms that the initiation of sexual intercourse before the age of 18 years, having history of sexually transmitted infection, and two or more lifetime sexual partners were determinants for precancerous cervical lesions. So that it should be focused on prevention through early detection and treatment of sexually transmitted infection with condom promotion. Women with a higher risk of precancerous lesions should also be encouraged to be screened more frequently for cervical cancer. [ABSTRACT FROM AUTHOR]

Background: miR-4429 acts as an inhibitor in many malignant tumors and participates in the biological processes of them, but the clinical value and potential molecular mechanism of miR-4429 in cervical cancer (CC) are still under investigation. Objective: To analyze the clinical value and molecular mechanism of miR-4429 in CC. Materials and Methods: A qRT-PCR assay was employed to determine the levels of miR-4429 and forkhead-box M1 (FOXM1) in CC tissues, CC cell lines (SiHa, CaSki, ME-180, and C33A) and human normal immortalized epithelial cell lines (HaCaT). The proliferation, migration, invasion, and apoptosis abilities of ME-180 and C33A cells were detected, and the epithelial-to-mesenchymal transition (EMT)-related proteins in the cells were also determined. Results: MiR-4429 acted as a tumor suppressor gene in CC tissues and cells and was linked to lymph node metastasis and International Federation of Gynecology and Obstetrics (FIGO) staging. The survival analysis revealed that lymph node metastasis, high FIGO staging, and low miR-4429 expression were all related to the unfavorable prognosis of the patients, and the dual-luciferase reporter assay revealed that FOXM1 was the target of miR-4429. Both overexpression of miR-4429 and knock-down of FOXM1 inhibited the proliferation, migration, invasion, and EMT of CCCs, and accelerated the apoptosis of them. Conversely, both knockdown of miR-4429 and overexpression of FOXM1 promoted those biological behaviors of the cells. Moreover, the rescue experiment revealed that the overexpression of FOXM1 reversed the influences of miR-4429 overexpression on the proliferation, migration, invasion, and EMT of CCCs. Conclusion: miR-4429 acts as a tumor suppressor in CC and can directly target FOXM1 to regulate the proliferation, migration, invasion, apoptosis and EMT of CCCs, so miR-4429 is expected to be a new therapeutic target for CC. [ABSTRACT FROM AUTHOR]

Purpose: External pelvic chemoradiotherapy and image-guided adaptive brachytherapy (IGABT) were studied in advanced cervical carcinomas. Treatment modalities were defined and related to outcomes and side effects. Material and methods: From a single cancer center, 138 patients with advanced cervical cancer were recruited. All patients were treated with external radiotherapy and IGABT. A dosimetric study was performed and related to treatment outcome and side effects. Toxicity of the organs at risk was evaluated by the CTCAE-grading system. Results: The median follow-up was 44 months. More than 60% of the tumors were FIGO stage IIB-IIIB and 82% were squamous cell carcinomas. Largest tumor size (width) was in mean 41 mm and 27% had lymph node spread. The mean total external dose was 51 Gy, and the mean total dose to the high-risk clinical target volume (HRCTV) was 88 Gy. In 130 patients (94%), weekly cisplatin was given in 4-6 cycles. The median number of brachytherapy fractions was four, and in 86 patients, interstitial needles were applied. The primary local control was 97% and 94% after four local recurrences. The overall pelvic control was 89%. The overall recurrence rate was 25% and distant metastases rate was 22%. The overall 5-year survival rate was 65% and cancer-specific survival rate was 69%. Prognostic factors were FIGO stage and total brachytherapy dose (D90) to HRCTV. Late serious toxicity of the bladder and intestine were rare, occurring in only 3% of patients. Conclusions: The local and pelvic control rates were excellent in this series. The IGABT was an important part of the treatment schedule and could probably not be replaced by increasing the external pelvic dose. Adenocarcinomas seemed to benefit from the addition of interstitial needles. Late serious toxicity was rare. [ABSTRACT FROM AUTHOR]

High risk human Papillomavirus (HPV) infections ultimately cause cervical cancer. Human Immunodeficiency Virus (HIV) infected women often present with multiple high-risk HPV infections and are thus at a higher risk of developing cervical cancer. However, information on the circulating high-risk HPV genotypes in Kenya in both HIV-infected and HIV-uninfected women is still scanty. This study is aimed at determining the phylogeny and the HPV genotypes in women with respect to their HIV status and at correlating this with cytology results. This study was carried out among women attending the Reproductive Health Clinic at Kenyatta National Hospital, a referral hospital in Nairobi, Kenya. A cross-sectional study recruited a total of 217 women aged 18 to 50 years. Paired blood and cervical samples were obtained from consenting participants. Blood was used for serological HIV screening while cervical smears were used for cytology followed by HPV DNA extraction, HPV DNA PCR amplification, and phylogenetic analysis. Out of 217 participants, 29 (13.4%) were HIV seropositive, while 68 (31.3%) were positive for HPV DNA. Eight (3.7%) of the participants had abnormal cervical cytology. High-risk HPV 16 was the most prevalent followed by HPV 81, 73, 35, and 52. One participant had cervical cancer, was HIV infected, and had multiple high-risk infections with HPV 26, 35, and 58. HPV 16, 6, and 81 had two variants each. HPV 16 in this study clustered with HPV from Iran and Africa. This study shows the circulation of other HPV 35, 52, 73, 81, 31, 51, 45, 58, and 26 in the Kenyan population that play important roles in cancer etiology but are not included in the HPV vaccine. Data from this study could inform vaccination strategies. Additionally, this data will be useful in future epidemiological studies of HPV in Nairobi as the introduction or development of new variants can be detected. [ABSTRACT FROM AUTHOR]

Background: Sentinel lymph node (SLN) biopsy is an attractive technique that is widely performed in many oncological surgeries. However, the potential risks in SLN biopsy for cervical cancer remains largely unclear. Methods: Seventy-five patients with histologically confirmed cervical cancer were enrolled between May 2014 and June 2016. SLN biopsies were performed followed by pelvic lymphadenectomies and all resected nodes were labeled according to their anatomic areas. Only bilateral detections of SLNs were considered successful. Patients' clinicopathologic feature, performance of SLN detection, and distributions of lymph node metastases were analyzed. Results: Of the 75 enrolled patients, at least one SLN was detected in 69 (92.0%), including 33 in bilateral and 36 in unilateral. SLNs were most detected in the obturator area (52 of 69 patients, 75.4%) and 26 (37.7%) patients presented SLNs in more than one area of hemipelvis. Lymphovascular invasion was found to be the only factor that adversely influenced SLN detection, while the tumor diameter, growth type, histological grade, deep stromal invasion, and neoadjuvant chemotherapy showed no significant impacts. Patients with lymphovascular invasion showed a significantly higher rate to have unsuccessful detection (90.9% versus 41.5%, P < 0.001) and lymph node metastasis (40.9% versus 3.8%, P < 0.001) compared with those without. Nodal metastases were confirmed in 11 patients, of whom 9 (81.8%) had lymphovascular invasion and 7 (63.6%) had non-SLN metastasis. The most frequently involved SLNs were obturator nodes (9/11, 81.8%). In addition, the parametrial nodes also have a high rate to be positive (4/11, 36.4%), although they were relatively less identified as SLNs. Besides, 3 patients showed metastases in the laterals without SLN detected. Conclusions: In cervical cancer, lymphovascular invasion is a significant factor for unsuccessful SLN detection. The risk of having undetected metastasis is high when SLN is positive; therefore, further lymphadenectomy may be necessary for these patients. [ABSTRACT FROM AUTHOR]

Background: To characterize the MIAT expression in cervical cancer and elucidate its mechanistic involvement in the tumor biology of this disease. Methods: The relative expression of MIAT and miR-150 was determined by real-time PCR. Cell proliferation was measured by the CCK-8 and clonogenic assay. The anchorage-independent growth was evaluated by soft agar assay. The in vivo tumor progression was assayed with xenograft mice model. The regulatory effect of miR-150 on MIAT was interrogated by luciferase reporter assay. The endogenous CNKD1B protein was detected by western blotting. Results: The low expression of MIAT was characterized in cervical cancer, which associated with relatively poor prognosis. Ectopic expression of MIAT inhibited malignant growth of cervical cancer both in vitro and in vivo. Mechanistically, MIAT regulated CDKN1B expression via competition with miR-150, and miR-150-inhibition directly suppressed cervical cancer cell growth. Conclusions: Our study characterized the anti-tumor property of MIAT in cervical cancer and elucidated its competitively regulation of CDKN1B with miR-150. Our data highlighted the critical role of MIAT-miR-150-CDKN1B signaling axis in cervical cancer. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis and developmental mechanism of early-stage (FIGO 2009 IA2-IIA2) cervical cancer (CC) remain unclear. Seeking novel molecular biomarkers based on The Cancer Genome Atlas (TCGA) will facilitate the understanding of CC pathogenesis and help evaluate early-stage CC prognosis. Methods: To identify prognosis-related genes in early-stage CC, we analyzed TCGA mRNA-seq data and clinical data by univariate Cox and Kaplan–Meier plotter analyses. Differential expression analysis identified upregulated genes in early-stage CC. Combined with the genes correlated with unfavorable prognosis, we selected desmoglein-2 (DSG2) for further investigation. To detect DSG2 expression in early-stage CC, we used immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR) and western blotting. The relationship between the expression of DSG2 and clinical features was analyzed by the Chi square test. Cox analysis was applied to assess the relationship between CC overall survival (OS) and risk factors. The correlations between DSG2 expression and CC cell line proliferation and migration were investigated with Cell Counting Kit-8 (CCK-8) and migration assays. Results: There were 416 prognosis-related genes in early-stage CC. DSG2, matrix metallopeptidase 1 (MMP1), carbonic anhydrase IX (CA9), homeobox A1 (HOXA1), and serine protease inhibitor B3 (SERPINB3) were upregulated in early-stage CC compared with adjacent noncancerous tissue (ANT) and correlated with unfavorable prognosis. Among them, DSG2 was most significantly correlated with patient survival. Coexpression analysis indicated that DSG2 was probably involved in cell division, positive regulation of transferase activity, positive regulation of cell migration, EGFR upregulation pathway and regulation of lymphangiogenesis. IHC, qRT-PCR and western blotting showed that DSG2 expression was higher in CC than in normal tissue. Significant correlations were identified between DSG2 expression and several aggressive clinical features, including pelvic lymph node metastasis (PLNM). Multivariate Cox analysis showed that DSG2 and PLNM were independent prognostic factors for OS. DSG2 knockdown inhibited CC cell proliferation and migration. Conclusions: DSG2 is a biomarker that promotes tumor proliferation and metastasis and is correlated with poor prognosis in early-stage CC. [ABSTRACT FROM AUTHOR]

Purpose: Treatment of cervical precancer is the primary aim in secondary prevention of cervical cancer. The purpose of this study was to examine factors associated with treatment uptake among women with acetic acid/Lugol's iodine positive lesions identified by digital cervicography (DC) in a cervical cancer prevention program in Cameroon. Patients and Methods: We conducted a cross-sectional survey of medical records from 2013 to 2018 of 755 women in Cameroon who screened positive with acetic acid/Lugol's iodine in 2013. Results: Of the 755 women, 422 (55.9%) had treatment/biopsy on the same day or followed up later, but only 344 (45.6%) received treatment/biopsy and 333 (44.1%) were lost to follow-up. Overall, 180 (52.3%) of the 344 women were treated/biopsied the same day they were screened, and 164 (47.7%) were treated/biopsied after the initial visit. Women aged 30– 49 and HIV-positive women were significantly more likely to have received treatment or returned for treatment than women less than 30 and HIV-negative women. Of the 266 women who followed up at a later date, the lesions of 78 (29.3%) women regressed spontaneously without treatment. Women with low-grade lesions, HIV-negative women and women who had follow-up more than a year after the initial exam were significantly more likely to have spontaneous regression with regression rates of 30.6%, 32.1% and 62.2%, respectively (p< 0.001). Age was not a significant determinant of spontaneous regression (p=0.149). Conclusion: Efforts to increase treatment uptake are needed in this population, including adherence to same day "See and treat" policies. [ABSTRACT FROM AUTHOR]