Detection of aflatoxin B1 adducts in Mexican women with cervical lesions

2021 ◽  
pp. 1-12
Author(s):  
L. Díaz de León-Martínez ◽  
C.M. López-Mendoza ◽  
Y. Terán-Figueroa ◽  
R. Flores-Ramírez ◽  
F. Díaz-Barriga ◽  
...  

Cervical cancer (CC) is one of the most serious threats to the lives of women; co-factors in addition to oncogenic human papillomavirus (HPV) infection may be important in causing CC. Women in Mexico are exposed to dietary aflatoxin B1, a potent carcinogen, which may act as a co-factor, in inducing progression to CC. Scarce studies are addressing environmental risks associated with the development of CC, thus the study aimed to establish a relationship between the presence of AFB1 and the detection of human papillomavirus in the genome of Mexican women. Forty samples from cervical tissue of women infected with HPV were obtained; positive results regarding the HPV type (16 and/or 18) were found in 92.5% women and the presence of AFB1-DNA adducts were detected in 77.5% of the same positive HPV samples. Detection of AFB1-DNA adducts and genomic concentrations were correlated with the detection of two oncogenic types of HPV 16 and 18. AFB1-DNA positivity and higher genomic concentrations of AFB1-DNA adducts were correlated with an increased risk of oncogenic detection of HPV in cervical samples from women in Mexico. As a secondary objective, a hypothetical interaction of the adducts with the NRF2 pathway has been proposed, therefore activation of p62 and in turn E6 and E7 (HPV proteins) would inhibit the formation of autophagosomes, which would result in a presence or recurrence of CC.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Akouélé P. Kuassi-Kpede ◽  
Essolakina Dolou ◽  
Théodora M. Zohoncon ◽  
Ina Marie Angèle Traore ◽  
Gnatoulma Katawa ◽  
...  

Abstract Background The causative agent of cervical cancer referred to as Human papillomavirus (HPV) remains a real public health problem. Many countries in West Africa, such as Togo have no data on the high-risk HPV (HR-HPV) infection and genotypes distribution. In order to fill the knowledge gap in the field in Togo, the main objective of this study was to determine the prevalence of pre-cancerous lesions of the cervix and HR-HPV genotypes among Togolese women. Methods Samples were collected from 240 women by introducing a swab in the cervix. Then, the screening of precancerous cervical lesions using the visual inspection with acetic acid and lugol (VIA / VIL) was conducted. The HR-HPV genotypes were characterised by real-time multiplex PCR. Results Out of 240 women recruited, 128 (53.3%) were infected by HR-HPV. The most common genotypes were HPV 56 (22.7%), followed by HPV 51 (20.3%), HPV 31 (19.5%), HPV 52 (18.8%) and HPV 35 (17.2%). The least common genotypes were HPV 33 (2.3%) and HPV 16 (2.3%). Among the women, 1.3% (3/240) were positive to VIA/VIL. Conclusion This study allowed HR-HPV genotypes to be characterised for the first time in Lomé, Togo. This will help in mapping the HR-HPV genotypes in West Africa.


2021 ◽  
Author(s):  
Haoru Dong ◽  
Xinhua Shu ◽  
Qiang Xu ◽  
Chen Zhu ◽  
Andreas M. Kaufmann ◽  
...  

AbstractHuman papillomavirus (HPV) infection identified as a definitive human carcinogen is increasingly being recognized for its role in carcinogenesis of human cancers. Up to 38%–80% of head and neck squamous cell carcinoma (HNSCC) in oropharyngeal location (OPSCC) and nearly all cervical cancers contain the HPV genome which is implicated in causing cancer through its oncoproteins E6 and E7. Given by the biologically distinct HPV-related OPSCC and a more favorable prognosis compared to HPV-negative tumors, clinical trials on de-escalation treatment strategies for these patients have been studied. It is therefore raised the questions for the patient stratification if treatment de-escalation is feasible. Moreover, understanding the crosstalk of HPV-mediated malignancy and immunity with clinical insights from the proportional response rate to immune checkpoint blockade treatments in patients with HNSCC is of importance to substantially improve the treatment efficacy. This review discusses the biology of HPV-related HNSCC as well as successful clinically findings with promising candidates in the pipeline for future directions. With the advent of various sequencing technologies, further biomolecules associated with HPV-related HNSCC progression are currently being identified to be used as potential biomarkers or targets for clinical decisions throughout the continuum of cancer care.


2010 ◽  
Vol 84 (16) ◽  
pp. 8219-8230 ◽  
Author(s):  
Monika Somberg ◽  
Stefan Schwartz

ABSTRACT Our results presented here demonstrate that the most abundant human papillomavirus type 16 (HPV-16) mRNAs expressing the viral oncogenes E6 and E7 are regulated by cellular ASF/SF2, itself defined as a proto-oncogene and overexpressed in cervical cancer cells. We show that the most frequently used 3′-splice site on the HPV-16 genome, site SA3358, which is used to produce primarily E4, E6, and E7 mRNAs, is regulated by ASF/SF2. Splice site SA3358 is immediately followed by 15 potential binding sites for the splicing factor ASF/SF2. Recombinant ASF/SF2 binds to the cluster of ASF/SF2 sites. Mutational inactivation of all 15 sites abolished splicing to SA3358 and redirected splicing to the downstream-located, late 3′-splice site SA5639. Overexpression of a mutant ASF/SF2 protein that lacks the RS domain, also totally inhibited the usage of SA3358 and redirected splicing to the late 3′-splice site SA5639. The 15 ASF/SF2 binding sites could be replaced by an ASF/SF2-dependent, HIV-1-derived splicing enhancer named GAR. This enhancer was also inhibited by the mutant ASF/SF2 protein that lacks the RS domain. Finally, silencer RNA (siRNA)-mediated knockdown of ASF/SF2 caused a reduction in spliced HPV-16 mRNA levels. Taken together, our results demonstrate that the major HPV-16 3′-splice site SA3358 is dependent on ASF/SF2. SA3358 is used by the most abundantly expressed HPV-16 mRNAs, including those encoding E6 and E7. High levels of ASF/SF2 may therefore be a requirement for progression to cervical cancer. This is supported by our earlier findings that ASF/SF2 is overexpressed in high-grade cervical lesions and cervical cancer.


2017 ◽  
Vol 5 (3) ◽  
pp. 69-82 ◽  
Author(s):  
Sigrun Smola ◽  
Connie Trimble ◽  
Peter L. Stern

It is now recognized that the immune system can be a key component of restraint and control during the neoplastic process. Human papillomavirus (HPV)-associated cancers of the anogenital tract and oropharynx represent a significant clinical problem but there is a clear opportunity for immune targeting of the viral oncogene expression that drives cancer development. However, high-risk HPV infection of the target epithelium and the expression of the E6/E7 oncogenes can lead to early compromise of the innate immune system (loss of antigen-presenting cells) facilitating viral persistence and increased risk of cancer. In these circumstances, a succession of interacting and self-reinforcing events mediated through modulation of different immune receptors, chemokine and cytokine responses (CCL20; CCL2; CCR2; IL-6; CCR7; IL-12) further promote the generation of an immune suppressive microenvironment [increased levels of Tregs, Th17, myeloid-derived suppressor cells (MDSCs) and PD-L1]. The overexpression of E6/E7 expression also compromises the ability to repair cellular DNA, leading to genomic instability, with the acquisition of genetic changes providing for the selection of advantaged cancer cells including additional strategies for immune escape. Therapeutic vaccines targeting the HPV oncogenes have shown some encouraging success in some recent early-phase clinical trials tested in patients with HPV-associated high-grade anogenital lesions. A significant hurdle to success in more advanced disease will be the local and systemic immune suppressive factors. Interventions targeting the different immunosuppressive components can provide opportunity to release existing or generate new and effective antitumour immunity. Treatments that alter the protumour inflammatory environment including toll-like receptor stimulation, inhibition of IL-6-related pathways, immune-checkpoint inhibition, direct modulation of MDSCs, Tregs and macrophages could all be useful in combination with therapeutic HPV vaccination. Future progress in delivering successful immunotherapy will depend on the configuration of treatment protocols in an insightful and timely combination.


1994 ◽  
Vol 5 (5) ◽  
pp. 343-345 ◽  
Author(s):  
K A Ward ◽  
J R Houston ◽  
B E Lowry ◽  
R D Maw ◽  
W W Dinsmore

212 females attending a genitourinary medicine (GUM) clinic with first episode anogenital warts were screened by cervical cytology and colposcopy/histology for the presence of cervical epithelial abnormalities in keeping with infection by the human papillomavirus (HPV infection) and/or cervical intraepithelial neoplasia (CIN). The prevalence of cervical epithelial abnormalities detected by cervical cytology alone was 32%, rising to 56% after colposcopic examination. However, the majority of cervical lesions detected by colposcopy alone were of low grade (HPV infection and/or CIN I). Histologically confirmed high grade cervical lesions (CIN II or CIN III) were detected more frequently in those females in whom cervical cytological examination indicated dyskaryosis in keeping with any grade of CIN, compared to females without dyskaryotic changes on cervical smear ( P<0.05, chi-squared test with Yates' correction). Early colposcopy is indicated for females with anogenital warts in the presence of a cervical smear showing dyskaryosis in keeping with any grade of CIN, because of the statistically significant increased risk of detecting a potentially progressive high grade cervical lesion. In females without dyskaryotic changes on cervical smear, the value of early colposcopy is uncertain and warrants larger more long-term trials.


2020 ◽  
Author(s):  
Mohammad Farahmand ◽  
Seyed Hamidreza Monavari ◽  
Ahmad Tavakoli

Abstract Background: Homosexual men or men who have sex with men (MSM) are at increased risk of human papillomavirus (HPV) infection because of their high-risk sexual behaviors. In this large study, a meta-analytic approach was used to systematically analyze the literature to elucidate the prevalence and genotype distribution of anal, penile, oral, and urethral HPV infection among MSM in the world.Methods: To carry out this systematic review, five electronic databases were searched for relevant studies published from January 2012 through to November 2019, and pertinent data were collected from the eligible articles. The pooled HPV prevalences were calculated for each anatomical region using random-effect model weighted by the inverse variance method. Subgroup analyses were performed to identify the probable sources of heterogeneity. The meta-analysis was performed using the “Metaprop” function in the R package Meta.Results: The overall pooled prevalence of anal, penile, oral, and urethral HPV infection among MSM were 78.11 % (95% CI: 75.50%-80.52%), 36.26% (95% CI: 29.13%–44.05%), 17.33% (95% CI: 13.65%–21.75%), and 15.40% (95% CI: 7.86%–27.97%), respectively. Stratified analyses showed that the prevalences of HPV were significantly higher in HIV-positive than HIV-negative MSM. The most frequent HPV high-risk type detected in the anus, penis, and oral cavity was HPV-16 (20.32%, 4.96%, and 3.16%, respectively). Conclusion: HPV infection is on the dramatic rise in MSM because of high-risk sexual behaviors, strongly suggesting the increased risk of developing HPV-related diseases and malignancies in this population. Among different sexual orientations, male homosexuality is associated with the highest risk of acquiring sexually transmitted infections.


2003 ◽  
Vol 13 (4) ◽  
pp. 505-509 ◽  
Author(s):  
K. U. Petry ◽  
U. Scholz ◽  
B. Hollwitz ◽  
R. Von Wasielewski ◽  
C. J.L.M. Meijer

Cervical cancer is the most common malignant tumor among women in Tanzania and other countries in tropical Africa. Genital schistosomiasis has been proposed as a possible cofactor in the genesis of this malignant disease that might contribute to its high incidence in regions where bilharzias is endemic. One hundred nine Tanzanian patients from an area with endemic bilharzias who were transferred to a gynecologic out-patient clinic were age-matched with 109 German controls. In patients and controls, separate samples were taken for cytologic assessment and human papillomavirus (HPV) DNA detection using the Hybrid Capture 2 assay (HC2) and PCR (GP5+/6 +). Samples that tested positive for HPV DNA with general primers were re-tested with HPV type-specific primers. After application of 3% acetic acid, punch biopsies were taken from any cervical lesion. Patients were interviewed for recent symptoms or clinical history suggestive of bilharzias. Urine samples from all patients were examined for the presence of schistosoma hematobium ova. Additionally six Tanzanian patients with invasive cervical cancer were included for separate analysis. Patients and controls had an identical prevalence of HPV-DNA (21.5%) using HC2. Based on PCR results with general primers, the corresponding prevalence was 34.5% for Tanzanian cases and 26.9% for German controls. A history suggestive of bilharzias and/or active schistosomiasis were associated with a significantly increased risk for infection with high-risk HPV types. We conclude that infection with Schistosoma hematobium seems to favor persistent genital HPV infection either by traumatizing the genital epithelium and/or by local immunosuppression.


2019 ◽  
Vol 65 (5) ◽  
pp. 625-632 ◽  
Author(s):  
Aimée Denzeler Baptista ◽  
Carolina Xavier Simão ◽  
Vitoria Carvalho Guimarães dos Santos ◽  
Juliana Gil Melgaço ◽  
Silvia Maria Baeta Cavalcanti ◽  
...  

SUMMARY OBJECTIVE: Human papillomavirus (HPV) is the most prevalent sexually transmitted virus in the world and is associated with an increased risk of cervical cancer. The most effective approach to cervical cancer control continues to be screening through the preventive Papanicolaou test (Pap test). This study analyzes the knowledge of university students of health science programs as well as undergraduate courses in other areas of knowledge on important questions regarding HPV. METHOD: Four hundred and seventy-three university students completed a questionnaire assessing their overall knowledge regarding HPV infection, cervical cancer, and the Pap test. A descriptive analysis is presented, and multivariate analysis using logistic regression identified factors associated with HPV/cervical cancer information. RESULTS: Knowledge was higher for simple HPV-related and Pap test questions but was lower for HPV interrelations with genital warts and cervical cancer. Being from the health science fields and having high income were factors associated with greater knowledge. Only the minority of the participants recognized all the situations that increased the risk of virus infection presented in the questionnaire. CONCLUSIONS: These findings highlight the need for educational campaigns regarding HPV infection, its potential as a cervical cancer agent and the forms of prevention available.


2014 ◽  
Vol 39 (2) ◽  
pp. 86-90 ◽  
Author(s):  
T Rahman ◽  
S Tabassum ◽  
M Jahan ◽  
A Nessa ◽  
Dr Ashrafunnessa

Human papillomavirus (HPV) high risk genotype infection and HPV viral load influences the development of invasive cervical cancer and cervical intra-epithelial neoplasia (CIN). HPV DNA testing for screening of cervical cancers may play a potential role in its early detection and management. The present study detected HPV DNA and estimated HPV viral load in different types of cervical lesions among Bangladeshi women. Using the Hybrid Capture 2 (HC2) assay, HPV DNA was tested among 68 women between 25-70 years of age. A total of 13 (19.1%) cases were positive for HPV DNA. The highest viral load (501 x 10³ copies/ml) was detected in a patient with invasive carcinoma, while the lowest viral load (105 x 10³ copies/ml) was detected from a case of chronic cervicitis. The mean viral load in CIN I was 119.25 x 10³±12.5 x 10³ copies/ml (range: 110 x 10³ - 137 x 10³) and 208.50 x 10³ ± 0.59 x 10³ copies/ml (range: 139 x 10³-305 x 10³) in CIN II / III. Interestingly, HPV DNA was detected from a patient with normal cytological findings. Our study observed a moderate presence of high-risk HPV genotypes among women with cervical lesions. The HPV viral load varied with the age of the patients and stage of cervical lesions. The HC2 assay is a promising tool for diagnosing high-risk HPV infection especially before cytology tests show any abnormality. DOI: http://dx.doi.org/10.3329/bmrcb.v39i2.19648 Bangladesh Med Res Counc Bull 2013; 39: 86-90


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