Comparative Study Analysis of Epstein-Barr Virus Infection: Tissue Versus Blood Samples in Patients With Prostatic Adenocarcinoma and Its Correlation With Clinicopathological Parameters.

Prostate cancer (PCa) is the most frequently diagnosed cancer and a leading cause of cancer-related mortality in men. The diagnosis and treatment of PCa carry considerable medical, psychological, and economic implications. Among the risk factors contributing to cancer, viral infections, notably Epstein-Barr virus (EBV), play a significant role. It is recognized as an oncogenic virus associated with various lymphomas, nasopharyngeal carcinomas, and breast cancer cases but its role in PCa remains unclear. This study aims to contrast the prevalence of EBV in blood and tissue samples of PCa patients and assess its correlation with tumor clinicopathological criteria. In this prospective study, 50 fresh biopsies and 50 blood samples were collected from patients with a confirmed diagnosis of PCa. EBV DNA was detected using polymerase chain reaction (PCR). A statistical analysis was then conducted to examine the correlation between EBV prevalence and PCa clinicopathological characteristics. EBV DNA was detected in 38% of PCa blood samples and 64% of PCa tissue samples, with a higher prevalence in tissue samples (p = 0.009). The statistical analysis revealed a significant correlation between EBV infection and pathological Gleason score (p = 0.041) in PCa tissue, as well as pathological T-stage (p = 0.02) in PCa blood. The results show that patients with PCa have higher levels of EBV in their tissues than in their blood, suggesting that EBV may play an important role in the etiology of PCa. This paves the way for further research into the function of EBV as a potential biomarker in the development and progression of prostate carcinoma in order to combat oncogenic viruses.

Evaluating the Expression Levels of Human Endogenous Retrovirus-K 10 (HERV-K10) Gag as a Biomarker in Prostate Cancer Tissue.

Prostate cancer is one of the most common major health problems. Several risk factors are potentially involved in its development. Therefore, a biomarker capable of early diagnosis is necessary to facilitate the early detection and treatment of prostate cancer. Human endogenous retroviruses (HERVs) are abnormally expressed in various diseases. Our study aims to evaluate the specific role of HERV K-10 gag expressions in the progression of prostate cancer. For this, we collected a set of 50 prostate tumor tissue samples as well as 50 healthy tissue samples. After extracting RNA from the prostate samples, we analyzed the expression of HERV-K gag using quantitative real-time PCR (qRT-PCR). The resulting data revealed a significant correlation of HERV-K gag expression in malignant regions of the prostate in men with prostate cancer than in men without prostate cancer (p < 0.05). The presence of the HERV-K gag protein was detected in 10 of 50 tumor samples (20%), while no healthy samples presented this protein. These results suggest that increased HERV-K gag RNA and protein expression could serve as a sensitive and specific biomarker of prostate malignancy in this cohort of prostate carcinoma patients, further supporting its potential as a promising clinical marker.

Prevalence of co-infection with human papillomavirus and Chlamydia trachomatis and risk factors associated with cervical cancer in Congolese women.

The human papillomavirus (HPV) is one of the most frequently diagnosed viruses in developing countries. Chlamydia trachomatis (CT) is an important cofactor in HPV-induced cervical cancer. Cervico-uterine smears were taken for cytology, and a total of 131 samples were analysed. HPV prevalence and CT were detected using specific primers (L1 gene and omp-1 gene). 23 (17.5 %) HPV-only samples were detected, CT-only positives were 10 (7.6 %). And HPV/CT co-infection was 13 (9.9 %). Identified risk factors associated with HPV/CT co-infection were risky sexual behaviour and cytology status. The prevalence of HPV and CT and their co-infection rates being high in our study population, may be an indicator of cervical cancer risk. Consequently, there is an urgent need to raise awareness and take appropriate precautions.

Detection of HPV in urine for cervical cancer screening: Feasibilty of an assay system.

The detection of urine HPV is considered as a promosing alternative to increase the screening coverage of cervical cancer. However, the validated assay of urine HPV is still scarse. We described a nouvel assay syetem for the urine-based detection of HPV in the framework of HPV screening. This sytsem consisted of Automate Nimbus extraction of DNA and Anyplex™ II HPV HR Detection PCR of HPV DNA. We validated this system by spiking HPV-infected cervical cancer cell line HeLa cells into normal urine and compared the prelimary results of cervical samples and urine samples. We found that this system could detect as few as 5 HeLa cells in normal urine model. Some discordances of HPV results between cervical samples and urine samples were observed. We concluded that this assay system could be applied for the detection of HPV in urine. A large scale study is necessary to evaluate the clinical significance of this assay system.

Germline mutations of B-Raf proto-oncogene and pathological implications in prostate cancer: observational study.

B-Raf proto-oncogene has been found in a variety of neoplasms. BRAF stimulation can promote tumour proliferation through the activation of the MAP/ERK kinase pathway. This study aimed to determine the germline spectra of BRAF and the association with pathological criteria of prostate tumours. Methods: Fifty blood samples from men treated with prostate cancer were analyzed for BRAF germline mutations and confirmed by Sanger sequencing, in addition, to establishing the frequencies and clinical correlations of frequent mutations in the BRAF gene for both exon 11 and exon 15. The frequency and distribution of high-frequency mutations were analyzed according to the pathological criteria of the patients. Results: Frameshift mutations: c.1628_1629insA and c.1624_1625insT with a frequency of (46%) and (18%), respectively, Nonsense mutations: c.1181C>A (p.Ser394Ter) was detected in one patient, missense mutations: c.1226A>G (p.Gln409Arg), c.1270T>C (p.Trp424Arg), c.1270_1271delins2 (p.Trp424Leu), with a frequency of (4%) were detected. There was no significant difference between mutation carriers and non-carriers regarding medical and surgical history, but prostate-specific antigen concentration was significantly different between the two groups. Conclusion: The results of this study elucidate the presence and involvement of germline mutations in prostate cancer, which could serve as a potential indicator for the diagnosis and therapeutic management of prostate cancer in the population studied.

Urine-based detection of HPV for cervical cancer screening: Time for standardized tests.

Cervical cancer is preventable because it has an established etiology, mainly attributed to a detectable pathogen, human papillomavirus (HPV). In 2018, the world health organization issued an unprecedented call for global action to eliminate cervical cancer by 2030. The adaptation of regular screening programs is fundamental to achieve the goal of cervical cancer elimination. However, it is still difficult to achieve satisfactory coverage rates of screening in developing countries as well as in developed countries because many women are reluctant to participate in gynecologic examination. HPV detection in urine is a convenient, widely acceptable by women and relatively affordable without the necessity for clinical visits to improve the coverage rates of cervical cancer screening. Unfortunately, the clinical implementation of urine-based tests for HPV detection has been hindered by the lack of standardized tests. Further optimization of protocols and standardization of urinary HPV detection are expected to be realized. With the advantages of urine sampling to overcome cost, personal, and cultural barriers, time has come for the standardized tests to facilitate a wide clinical implementation of urinary HPV detection that will significantly contribute to the WHO's goal, that is, to eliminate the cervical cancer globally.

Molecular evaluation of human papillomavirus as an oncogenic biomarker in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is one of the most common tumors in men, regardless of ethnicity and demographics. In many risk factors causing PCa, genes and viral infections are strong candidates for the development of prostate tumors. Indeed, tissue infections of PCa have been reported by the presence of several types of viruses including Human Papillomaviruses (HPV). OBJECTIVE: the present study was planned to determine whether HPV DNA could be detected in the blood of known men with prostate cancer and to assess the potential association between HPV infection and clinico-pathological characteristics of the patients. MATERIALS AND METHODS: In order to achieve our objectives, 150 liquid blood samples were taken from Moroccan patients, 100 patients with PCa, and 50 control cases. The viral DNA was extracted, calibrated and the target genes were amplified by PCR using specific primers and the use of 2% agarose gel with visualization under UV. RESULTS: Of the 100 samples tested, (10%) were infected with HPV), However, none of the control cases were infected with HPV. The analysis of the data made it possible to establish a correlation between the frequency of the viral infection of the human papilloma and the tumoral criteria. CONCLUSION: Therefore, this study strengthens the potential role of HPV as a cofactor in prostate cancer development, and we propose that infection with this virus may be involved in the development of PCa metastases.

Molecular characterization of human papillomavirus and mouse mammary tumor virus-like infections in prostate cancer tissue and relevance with tumor characteristics.

The suspected roles of human Papillomavirus (HPV) and mouse mammary tumor virus (MMTV) infections in prostate tumor development were recently reported. To detect the frequency of HPV and MMTV-like infections and clinical correlates of tumor characteristics, DNA samples from 50 men treated at Teaching Hospital of Rabat City (Morocco) between June 2017 and February 2019, were genotyped and confirmed by Sanger sequencing. Eight infections of HPV18 and two infections of MMTV-like were detected, and 50% of patients were at a Gleason score of 6. A significant association between Gleason score and HPV or MMTV-like infection was noted (P=0.0008); 90% of patients with viral infections presented with T1 and T2 pathological stage tumors. Yet, no significant differences were found between infected and noninfected men regarding other pathological parameters including prostate-specific antigen (PSA), tumor histological stage, age at diagnosis and radical prostatectomy treatment (P=0.2179, 0.4702, 0.8101, and 0.9644, respectively). The molecular evolution of HPV and MMTV in comparison with previously aligned sequences was discussed. Our findings provide a highlight on the correlations between the clinical-pathological parameters of prostate tumors and HPV and MMTV infections. Prospective studies with a wide sample size are needed for more statistical clarification of the association between viral infections with prostate tumor criteria.

Prevalence of specific and recurrent/founder pathogenic variants in BRCA genes in breast and ovarian cancer in North Africa.

BACKGROUND: Elucidation of specific and recurrent/founder pathogenic variants (PVs) in BRCA (BRCA1 and BRCA2) genes can make the genetic testing, for breast cancer (BC) and/or ovarian cancer (OC), affordable for developing nations. METHODS: To establish the knowledge about BRCA PVs and to determine the prevalence of the specific and recurrent/founder variants in BRCA genes in BC and/or OC women in North Africa, a systematic review was conducted in Morocco, Algeria, and Tunisia. RESULTS: Search of the databases yielded 25 relevant references, including eleven studies in Morocco, five in Algeria, and nine in Tunisia. Overall, 15 studies investigated both BRCA1 and BRCA2 genes, four studies examined the entire coding region of the BRCA1 gene, and six studies in which the analysis was limited to a few BRCA1 and/or BRCA2 exons. Overall, 76 PVs (44 in BRCA1 and32 in BRCA2) were identified in 196 BC and/or OC patients (129 BRCA1 and 67 BRCA2 carriers). Eighteen of the 76 (23.7%) PVs [10/44 (22.7%) in BRCA1 and 8/32 (25%) in BRCA2] were reported for the first time and considered to be novel PVs. Among those identified as unlikely to be of North African origin, the BRCA1 c.68_69del and BRCA1 c.5266dupC Jewish founder alleles and PVs that have been reported as recurrent/founder variants in European populations (ex: BRCA1 c.181T>G, BRCA1 c1016dupA). The most well characterized PVs are four in BRCA1 gene [c.211dupA (14.7%), c.798_799detTT (14%), c.5266dup (8.5%), c.5309G>T (7.8%), c.3279delC (4.7%)] and one in BRCA2 [c.1310_1313detAAGA (38.9%)]. The c.211dupA and c.5309G>T PVs were identified as specific founder variants in Tunisia and Morocco, accounting for 35.2% (19/54) and 20.4% (10/49) of total established BRCA1 PVs, respectively. c.798_799delTT variant was identified in 14% (18/129) of all BRCA1 North African carriers, suggesting a founder allele. A broad spectrum of recurrent variants including BRCA1 3279delC, BRCA1 c.5266dup and BRCA2 c.1310_1313detAAGA was detected in 42 patients. BRCA1 founder variants explain around 36.4% (47/129) of BC and outnumber BRCA2 founder variants by a ratio of ≈3:1. CONCLUSIONS: Testing BC and/or OC patients for the panel of specific and recurrent/founder PVs might be the most cost-effective molecular diagnosis strategy.

Human papilloma virus profiles in breast cancer in correlation with Vitamin D.

The major roles of vitamin D in the genesis of breast cancer and as an immunomodulator against acute and chronic infections have been the subject of much research in recent years. A low vitamin D status could decrease the function of blocking the cell multiplication cycle of the cancer process and weaken the immune system. In this context, we were interested in the implication of vitamin D status in women with human papilloma virus (HPV)-induced breast cancer. Our study included 63 women, 53 with breast cancer and 10 healthy women, and we measured the plasma 25(OH)D3 level and looked for the presence of HPV by PCR in our population. 90.6% had low serum 25(OH)D3 levels and HPV was found in 41% of cases. In this regard, the data in the literature are discordant. Vitamin D status could explain the concomitance of the two conditions, breast cancer and HPV; it would be desirable to broaden the sample in order to better define its impact.

The Biological Significance of Long noncoding RNAs Dysregulation and their Mechanism of Regulating Signaling Pathways in Cervical Cancer.

Despite the remarkable decrease in cervical cancer incidence due to the availability of the HPV vaccine and implementation of screening programs for early detection in developed countries, this cancer remains a major health problem globally, especially in developing countries where most of the cases and mortality occur. Therefore, more understanding of molecular mechanisms of cervical cancer development might lead to the discovery of more effective diagnosis and treatment options. Research on long noncoding RNAs (lncRNAs) demonstrates the important roles of these molecules in many physiological processes and diseases, especially cancer. In the present review, we discussed the significance of lncRNAs altered expression in cervical cancer, highlighting their roles in regulating highly conserved signaling pathways, such as mitogen-activated protein kinase (MAPK), Wnt/ß-catenin, Notch, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways and their association with the progression of cervical cancer in order to bring more insight and understanding of this disease and their potential implications in cancer diagnosis and therapy.

Detection of hypermethylation BRCA1/2 gene promoter in breast tumours among Moroccan women.

BACKGROUND: The promoter region is a key element of gene expression regulation. In mammals, most of the genes present, at the level of their promoter, a large number of islands CpG. Age also is seen as another factor for developing breast cell cancer reaching the tumour stage. AIM: This study aimed to explore the hypermethylation of the BRCA1/2 promoter gene in women breast cancer and correlation with age and tumour stage. MATERIALS AND METHODS: Fifty biopsies were derived from Moroccan women treated for breast carcinoma, the DNA extracted was treated by bisulphite and the targeted BRCA1/2 Amplicons were amplified by specific methylation primers (MSP). RESULTS: The result shows that 62% of the samples were BRCA1 methylated in addition and negative result for BRCA2, these positive epigenetic factor were remarkable in women over 47 years and at the stage of malignant tumour. CONCLUSION: These results show that half of the methylated samples are positive with a majority of over 47 years old, and confirms that age might be an additional factor for breast cancer development.

Helicobacter pylori co-infection with Epstein-Barr virus and the risk of developing gastric adenocarcinoma at an early age: Observational study infectious agents and cancer.

BACKGROUND: Gastric cancer (GC) is one of the leading causes of morbidity and mortality worldwide. The onset and progression of gastric cancer are attributed to numerous triggers, these triggers may be infection of the gastric epithelium by Helicobacter pylori (H. pylori), or by Epstein-Barr virus (EBV). Both agents can establish a lifelong persistent infection in the host, leading to chronic inflammation, which also contributes to cancer development. Objective: The objective of this study is to present the status of co-infection with H. pylori and EBV and the risk of developing adenocarcinoma at an early age in the population of Grand Casablanca. METHODS: In this study, 100 gastric tissue samples from patients with gastric cancer were examined for detection of H. pylori and EBV in tumor tissue using PCR techniques, and the clinical relevance was statistically analyzed. RESULTS: Results revealed an individual Epstein-Barr virus (EBV) infection observed in (40 %) of gastric carcinoma cases. Furthermore, the frequency of EBV infection was significantly different with intestinal and diffuse gastric cancer types [15 % vs. 85 %; <0.05]. The prevalence of individual H. pylori infections was 34 %, while the frequency of co-infection was 16 %. Moreover, no significant association was found between co-infection and sex, tumor grade, stage, and lymph node metastasis, but there was a significant association between co-infection and the age of GC patients. CONCLUSION: Thus understanding the status of co-infection could clarify the process of gastric carcinogenesis, and application of this knowledge for clinical purposes could facilitate diagnosis, risk management, and prevention.

Diagnostic Value of MicroRNA 21 in Endometrial Cancer and Benign Lesions and its Differential Expression with Clinicopathological Parameters.

BACKGROUND: Endometrial cancer is one of the most common malignancies among women worldwide. Although this cancer is often diagnosed at early stages, the need for biomarkers of diagnosis remains a necessity to overcome conventional invasive procedures of diagnosis. OBJECTIVE: In our study, we aim to investigate the diagnostic value of microRNA-21 in endometrial cancer and its relation to clinicopathological features. METHODS: We used RT-qPCR to measure the expression of microRNA-21 in 71 tumor tissues, 53 adjacent tissues, and 54 benign lesions. RESULTS: Our results show that microRNA-21 is a potential biomarker for endometrial cancer with an area under the receiver operating characteristic curve of 0.925 (95% CI = 0.863 - 0.964, P<0.0001). The sensitivity was 84.51% (95% CI = 74.0 - 92.0) and specificity was 86.79% (95% CI = 74.7 - 94.5). For discrimination between benign lesions and controls the AUC was 0,881 with a sensitivity of 100% (95% CI = 93.4 - 100.0) and specificity of 66.04% (95% CI = 51.7 - 78.5), and for discriminating benign lesions from tumors the AUC was 0,750 with a sensitivity of 54.93% (95% CI = 42.7 - 66.8) and specificity of 90.74% (95% CI = 79.7 - 96.9). We also found that tumors with elevated microRNA-21 expression are of advanced FIGO stage, high histological grades, and have cervical invasion, myometrial invasion and distant metastasis. CONCLUSION: Our findings support the important role of miR-21 as a biomarker to diagnose endometrial cancer. Further studies on minimally invasive/noninvasive samples such as serum, blood, and urine are necessary to provide a better alternative to current diagnosis methods.

Association between Gene Promoter Methylation and Cervical Cancer Development: Global Distribution and A Meta-analysis.

DNA methylation is the main epigenetic event for gene silencing and is associated with carcinogenesis. In this meta-analysis, we evaluated the association between the methylation of the promoter regions of APC, CADM1, CCNA1, CDH1, DAPK, FHIT, HIC1, MAL, MGMT, hMLH1, P16, PAX1, RAR-ß, and RASSF1 genes and the risk of cervical cancer development and progression. Overall, 194 eligible studies were identified assessing the associations of promoter methylation status of aforementioned genes with low- and high-grade squamous intraepithelial lesions (LSIL and HSIL) and cervical cancer development. The majority of studies were conducted on Caucasian and Asian populations, whereas rare studies were available on the African population. Promoter methylation frequencies were shown to be significantly higher in LSIL and HSIL cervical cancer cases as compared to control specimens for CADM1, CCNA1, CDH1, DAPK1, FHIT, MAL, P16, PAX1, RAR-ß, and RASSF1 genes. A moderate association was found between HIC promoter methylation, whereas APC, MGMT, and hMLH1 promoter methylation was not correlated with cervical cancer development. Promoter methylation could be considered as a noninvasive biomarker for early cervical lesions, making them highly promising targets for a personalized therapeutic approach.

HPV16 L1 diversity and its potential impact on the vaccination-induced immunity.

Human Papillomavirus 16 (HPV16) is the most oncogenic HPV and the most associated genotype with cervical cancer development and progression. Currently, all developed vaccines are targeting HPV16 and were designed based on the major L1 capsid protein. Thus, evaluation of the diversity of HPV16 L1 sequence, mainly in the antigenic regions, will be of a great interest to assess the efficacy of the prophylactic vaccines and to predict the impact of genetic variations in these regions on the vaccination-induced immunity. A total of 377 HPV16 L1 sequences, published in public domain GenBank database, from the Americas, Africa, Asia, and Europe were collected and assembled. A total of 626 mutation events affecting 83 distinct nucleotides into the five antigenic regions of L1 gene of HPV16 were reported, and most SNPs were located in DE (27.38%, 23/83) and FG (31%, 26/83) loops. Overall, 4 mutations were frequently found in HPV16 sequences: T176N and N181T in EF loop; A266T in the FG loop and T353P/I/N HI loop. Of particular interest, some SNPs are ubiquitous and were found in all populations whereas others were population specific and their presence was limited to one or 2 at the maximum. Association between mutations in the antigenic regions and ethnicity was also investigated and showed that mutations in BC and DE loops were present with no significant difference in sequences from Europe, Asia, America and Africa. However, most mutations in FG loop are reported in sequences from European cases and are less pronounced in cases from America and Asia, whereas mutations EF and HI loops prevail in Asian cases. These data highlight a high number of variant amino acid residues that could affect the vaccination-induced immunity and impact the effectiveness of the prophylactic vaccination to fight against HPV, warranting the need of further investigation for vaccines and natural history studies of HPV16.

Tuberculosis of the breast: analysis of 17 cases.

Tuberculosis constitutes a major public health problem in the world. Certain extra-pulmonary locations of tuberculosis disease are very exceptional. Amongst these, tuberculosis of the breast is rare even in countries where this infection is endemic. This form of tuberculosis is characterized by clinical and radiological polymorphisms and might mimic other diseases, especially breast cancer. This retrospective study is entailing seventeen patients treated in the Onco-Gynecology Department of the Mohammed VI Cancer Treatment Center, in the Ibn Rochd University Hospital of Casablanca, for breast tuberculosis, over a period of three years. We report the epidemiological, clinical and paraclinical aspects and we specify the treatment and evolution of the patients.

Oncogenic Human Papillomavirus involvement in epithelial ovarian carcinoma among women in Morocco.

Epithelial Ovarian cancer (EOC) although rare is the most lethal gynecological cancer in women worldwide. Despite its high prevalence few studies have been performed to evaluate the prevalence and determinants of HPV infection worldwide. The aim of the present study was to investigate the presence of HPV-DNA in Moroccan patients with EOC using PCR among women in Casablanca, and to examine the prevalence of some HPV genotypes in Moroccan population. We performed a study of HPV detection on Fresh biopsies of 70 epithelial ovarian cancer patients. PCR was realized using the MY09/11 and GP5+/6+ primers. Genotyping of HPV was performed by PCR typespecific for HPV 6, 11, 16, 18, 31, and 33.Data was statistically analyzed using SPSS software. Hence, the mean age was 48.9 years (range,21-76 years). Serous adeno carcinoma (75.71%) and stage III of the disease represent the majority of cases. eight patients were HPV positive (11.42%).Results of HPV genotyping revealed predominance of two genotypes: HPV 16 (87.5%) and HPV 31(12.5).No co-infection identified. Approximately 75% of positive cases had a serous cystadeno carcinoma and more than 62,5% had FIGO advanced stage (III or IV).Our study showed that high-risk HPV infection could play a major role among patients with EOC in Morocco.