Project description:Human papillomavirus (HPV)16 is the most oncogenic human papillomavirus, responsible for most papillomavirus-induced anogenital cancers. We have explored by sequencing and phylogenetic analysis the viral variant lineages present in 692 HPV16-monoinfected invasive anogenital cancers from Europe, Asia, and Central/South America. We have assessed the contribution of geography and anatomy to the differential prevalence of HPV16 variants and to the nonsynonymous E6 T350G polymorphism. Most (68%) of the variance in the distribution of HPV16 variants was accounted for by the differential abundance of the different viral lineages. The most prevalent variant (above 70% prevalence) in all regions and in all locations was HPV16_A1-3, except in Asia, where HPV16_A4 predominated in anal cancers. The differential prevalence of variants as a function of geographical origin explained 9% of the variance, and the differential prevalence of variants as a function of anatomical location accounted for less than 3% of the variance. Despite containing similar repertoires of HPV16 variants, we confirm the worldwide trend of cervical cancers being diagnosed significantly earlier than other anogenital cancers (early fifties vs. early sixties). Frequencies for alleles in the HPV16 E6 T350G polymorphism were similar across anogenital cancers from the same geographical origin. Interestingly, anogenital cancers from Central/South America displayed higher 350G allele frequencies also within HPV16_A1-3 lineage compared with Europe. Our results demonstrate ample variation in HPV16 variants prevalence in anogenital cancers, which is partly explained by the geographical origin of the sample and only marginally explained by the anatomical location of the lesion, suggesting that tissue specialization is not essential evolutionary forces shaping HPV16 diversity in anogenital cancers.
Project description:In spite of the well-established understanding of the phenotypic lesions occurring in the shift from native epithelia to invasive (adeno) carcinoma, the molecular typing of the precancerous changes in the gastrointestinal tract remains unreliable. In recent years, no biomarkers have aroused as much interest as the miRNAs, a class of non-coding RNA molecules that function as endogenous silencers of numerous target genes. Aberrant miRNA expression is a hallmark of human disease, including cancer. Unlike most mRNAs, miRNAs are both long-living in vivo and very stable in vitro. Such characteristics allow their testing in paraffin-embedded tissue samples, which is essential in the biological profiling of small (phenotypically characterized) preneoplastic lesions of the gastrointestinal tract (as well as in other fields of human pathology). The upcoming challenge lies in the reliable identification of disease-specific targets of dysregulated miRNAs, to enable miRNA testing in the clinical management of the secondary prevention of gastrointestinal cancer.
Project description:IntroductionPrecancerous lesions of the cervix are changes in cervical cells that make them more likely to develop into cancer. Understanding the prevalence and determinants of the precancerous lesions of the cervix among women helps to take an action like vaccination programs, improving screening coverage, and close management and follow-up which could decrease the morbidity and mortality caused by cervical cancer.Materials and methodsThe international databases, PubMed/MEDLINE, Web of Science, EMBASE, CINAHL, Google Scholar, Science Direct and Cochrane Library and unpublished reports were systematically searched. Two authors independently extracted all necessary data using a standardized data extraction format. STATA 14 statistical software was employed to analyse the data. The Cochrane Q test statistics and I2 tests were used to assess the heterogeneity between the studies. A random-effect model was computed to estimate the pooled prevalence of precancerous lesions of the cervix in Ethiopia. Determinants of the precancerous lesion of cervix (early initiation of sexual intercourse, multiple sexual partners, and history of sexually transmitted infection) were analysed.ResultsThirteen studies fulfilled the inclusion criteria and included in the meta-analysis. The I2 test result showed high heterogeneity (I2, 93.2%, p = <0.001). Using the random effect analysis, the pooled prevalence of precancerous lesions of the cervix among women in Ethiopia was 14.21% (95% CI (10.49, 17.94). After adjusting of publication bias using trim-and-fill method, the pooled prevalence was 9.43% (95% CI (5.23, 13.62). Women who had multiple sexual partners in their lifetime (OR:2.67 CI: 1.49,4.79) and had a history of sexually transmitted infections (OR:6.22 CI: 2.99,12.92) were more likely to have a precancerous lesion of the cervix.ConclusionThe pooled prevalence of the precancerous lesions of the cervix among Ethiopian women was 9.43%. It was associated with having multiple sexual partners and a history of sexually transmitted infections.
Project description:To evaluate the clinical accuracy of Hepika test to identify cancer/precancerous lesions of the uterine cervix. A multicentre retrospective study was carried out in 2018 and included 330 liquid-based cytology samples from three Italian centres of women aged 25-64 who had been tested for the human papillomavirus (HPV) and whose histology or follow-up outcome was known. Hepika is an enzyme-linked immunosorbent assay (ELISA) targeting the protein complexes E6#p53 and E7#pRb. After excluding samples without sufficient residual material, the clinical accuracy of Hepika test was evaluated in 274 samples: adenocarcinoma (ADC) (4), squamous cell carcinoma (SCC) (7), adenocarcinoma in situ (AIS) (1), cervical intraepithelial neoplasia (CIN) grade 3 (60), CIN2 (51), CIN1 (34), and negative histology (117). Association, sensitivity, and specificity for carcinoma, CIN3+ and CIN2+ are reported. Positive Hepika test was associated with a high probability of carcinoma (odds ratio (DOR) = 33.68, 95% confidence interval (CI) 7.0-163.1); sensitivity was 81.8%, specificity, 88.2%. A positive Hepika test showed a weaker association with CIN3+ lesions (DOR = 3.5; 95% CI 1.75-6.99) and lower sensitivity (27.8%). The Hepika test was found to be an accurate biomarker for HPV-induced cervical carcinoma. Population-based prospective studies are needed to confirm the clinical usefulness of the Hepika test in the differential diagnosis of HPV-induced invasive lesions.
Project description:IntroductionThe simplest and cheapest method for cervical cancer screening is visual inspection after application of acetic acid (VIA). However, this method has limitations for correctly identifying precancerous cervical lesions (sensitivity) and women free from these lesions (specificity). We will assess alternative screening methods that could improve sensitivity and specificity in women living with humanimmunodeficiency virus (WLHIV) in Southern Africa.Methods and analysisWe will conduct a paired, prospective, screening test accuracy study among consecutive, eligible women aged 18-65 years receiving treatment for HIV/AIDS at Kanyama Hospital, Lusaka, Zambia. We will assess a portable magnification device (Gynocular, Gynius Plus AB, Sweden) based on the Swede score assessment of the cervix, test for high-risk subtypes of human papillomavirus (HR-HPV, GeneXpert, Cepheid, USA) and VIA. All study participants will receive all three tests and the reference standard at baseline and at six-month follow-up. The reference standard is histological assessment of two to four biopsies of the transformation zone. The primary histological endpoint is cervical intraepithelial neoplasia grade two and above (CIN2+). Women who are VIA-positive or have histologically confirmed CIN2+ lesions will be treated as per national guidelines. We plan to enrol 450 women. Primary outcome measures for test accuracy include sensitivity and specificity of each stand-alone test. In the secondary analyses, we will evaluate the combination of tests. Pre-planned additional studies include use of cervigrams to test an automated visual assessment tool using image pattern recognition, cost-analysis and associations with trichomoniasis.Ethics and disseminationEthical approval was obtained from the University of Zambia Biomedical Research Ethics Committee, Zambian National Health Regulatory Authority, Zambia Medicines Regulatory Authority, Swissethics and the International Agency for Research on Cancer Ethics Committee. Results of the study will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT03931083; Pre-results.
Project description:BACKGROUND:Vulvar melanoma (VuM) and vaginal melanoma (VaM) represent a unique subgroup of malignant melanomas with important differences in biology and treatment. OBJECTIVE:The objective of this study was to describe the epidemiology and prognosis of VuM and VaM in a large representative cohort. METHODS:Women with invasive VuM or VaM were identified from the Surveillance, Epidemiology and End Results-18 population representing 27.8% of the US population. Data on age, ethnicity, stage, location, histopathology, primary surgery, and lymphadenectomy were collected. The Kaplan-Meier method was used to analyze disease-specific and overall survival. Univariate and multivariate regression models were used to identify factors with a significant association with disease-specific survival. RESULTS:A total of 1400 VuM and 463 VaM were included for further analysis; 78.6% and 49.7% of women with VuM and VaM underwent surgery, but only 52.9% of women with non-metastatic VuM and 42.9% of women with non-metastatic VaM undergoing surgery had lymph node assessment; one third of these had positive nodes. Superficial spreading was the most common subtype in VuM, and nodular melanoma in VaM (p?<?0.001). The median disease-specific survival was 99 months (95% confidence interval 60-138) and 19 months (95% confidence interval 16-22), respectively. Survival was significantly associated with age at diagnosis, ethnicity, stage, surgery, lymph node metastases, histologic subtype, ulceration, mitotic count, and tumor thickness in VuM, and stage, surgery, and lymph node involvement in VaM. In the Cox model, lymph node status and number of mitoses remained independent predictors of outcome in VuM; in VaM, only lymph node status remained significant. CONCLUSIONS:The overall prognosis of VuM and VaM remains poor. The American Joint Committee on Cancer staging system is applicable and should be used for VuM; however, lymph node status and mitotic rate are the most important predictors of survival. Lymph node status should be assessed and patients with positive nodes may be candidates for adjuvant treatment.
Project description:The tongue coating (TC) microbiota, a crucial component of the tongue coating, illustrates a huge microbial percentage of the body that mostly includes actinobacteria, bacteroides, firmicutes, and fusobacteria. The TC microbiota is closely related to the development of upper gastrointestinal malignancies, such as oral, gastric, and esophageal cancer. Nonetheless, the microbiological characteristics of common TCs in individuals with precancerous lesions of the upper gastrointestinal tract are still unclear. Herein, we designed a case-control study, recruiting 153 PLUGT patients with four different types of TCs, including 47 white-thin, 19 white-thick, 47 yellow-thin, and 40 yellow-thick, as well as 47 volunteers as controls. To analyze microbial characteristics, 16S rRNA microbiome approaches were used. An enzyme-linked immunosorbent assay (ELISA) was employed to assess serum IL-17A and total bile acid (TBA). According to the obtained results, Leptotrichia was found to be a promising biomarker for thin as well as thick yellow coatings. In comparison to the control TC microbiota, 39 different genera developed commensal networks in common TCs. Lachnoanaerobaculum and pseudonocardia were the most striking core bacteria. Lachnoanaerobaculum positively correlated with Leptotrichia in W-thin and Y-thick coatings, with actinomyces and methylobacterium in Y-thin coatings, with Campylobacter in Y-thick coatings, and with Bradyrhizobium in W-thick and Y-thick coatings. Serum IL-17A levels were greater in cases with W-thin coating than in controls, and serum IL-17A was positively linked with Parvimonas in patients with W-thick or Y-thin coating. In Y-thin coating, the oral dominating bacteria Streptococcus was negatively linked with serum TBA. Taken together, the promoted bacteria were found to be synergistically proliferative in the TCs of PLUGT patients. The diverse TCs had distinct bacterial commensal networks, whereas the common TCs were linked by specific bacteria to serum IL-17A and TBA.