Publications by authors named "Luisa Lina Villa"

111 Publications

Frequency of Human Papillomavirus Detection in Chagasic Megaesophagus Associated or Not with Esophageal Squamous Cell Carcinoma.

Pathobiology 2021 Oct 12:1-9. Epub 2021 Oct 12.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.

Background: Chagasic megaesophagus (CM) as well as the presence of human papillomavirus (HPV) has been reported as etiological factors for esophageal squamous cell carcinoma (ESCC).

Objective: We assessed the prevalence of HPV DNA in a series of ESCCs associated or not with CM. Data obtained were further correlated to the pathological and clinical data of affected individuals.

Methods: A retrospective study was performed on 92 formalin-fixed and paraffin-embedded tissues collected from patients referred to 3 different hospitals in São Paulo, Brazil: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro, Uberaba, Minas Gerais; and São Paulo State University, Botucatu, São Paulo. Cases were divided into 3 groups: (i) 24 patients with CM associated with ESCC (CM/ESCC); (ii) 37 patients with ESCC without CM (ESCC); and (iii) 31 patients with CM without ESCC (CM). Detection of HPV DNA was assessed in all samples by a genotyping assay combining multiplex polymerase chain reaction and bead-based Luminex technology.

Results: We identified a high prevalence of high-risk HPV in patients in the CM group (12/31, 38.8%) and CM/ESCC (8/24, 33.3%), compared to individuals in the ESCC group (6/37, 16.3%). The individuals in the groups with cancer (ESCC and CM/ESCC) had a higher frequency of HPV-16 (4/9, 44.5% and 2/8, 25.0%). The other types of high-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73. We also observed in some samples HPV coinfection by more than one viral type. Despite the high incidence of HPV, it did not show any association with the patient's clinical-pathological and molecular (TP53 mutation status) characteristics.

Conclusion: This is the first report of the presence of HPV DNA in CM associated with ESCC. HPV infection was more presence in megaesophagus lesions. Further studies are needed to confirm and better understand the role of persistent HPV infection in patients with CM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000518697DOI Listing
October 2021

Biomarkers of human papillomavirus (HPV)-driven head and neck cancer in Latin America and Europe study: Study design and HPV DNA/p16 status.

Head Neck 2021 Nov 2. Epub 2021 Nov 2.

Center for Translational Research in Oncology, Instituto do Cancer do Estado de Sao Paulo ICESP, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo FMUSP HC, Sao Paulo, Brazil.

Background: Human papillomavirus (HPV)-driven head/neck squamous cell carcinomas (HNSCC) prevalence varies globally. We evaluated HPV DNA and p16 in formalin fixed paraffin embedded (FFPE) HNSCC from Argentina, Brazil, Colombia, and Peru.

Methods: HPV was genotyped by PCR-hybridization. All HPV DNA positive and some HPV DNA negative cases underwent p16 immunohistochemistry.

Results: HPV DNA was detected in 32.8%, 11.1%, and 17.8% of oropharyngeal (OPC), oral cavity (OCC) and laryngeal (LC) cancers, respectively. OPC HPV prevalence was higher in Colombia (94.7%), and Argentina (42.6%) compared to Brazil (10.6%) and Peru (0.0%). HPV-16 was the most detected. Other HPVs were found in LC. Higher rates of p16 positivity were observed among HPV positive OPC/OCC cases compared to LC cases.

Conclusions: Our results support a role for HPV-16 in a subset of HNSCC, corroborate the heterogeneity observed in samples from different countries, and contribute additional etiological and biomarkers information in tumors of significant impact worldwide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.26912DOI Listing
November 2021

Disruption of miRNA-mRNA Networks Defines Novel Molecular Signatures for Penile Carcinogenesis.

Cancers (Basel) 2021 Sep 23;13(19). Epub 2021 Sep 23.

Departamento de Urologia, ICESP, HCFMUSP, Sao Paulo CEP 01246-000, SP, Brazil.

Penile cancer (PeC) carcinogenesis is not fully understood, and no biomarkers are reported in clinical practice. We aimed to investigate molecular signatures based on miRNA and mRNA and perform an integrative analysis to identify molecular drivers and pathways for PeC development. Affymetrix miRNA microarray was used to identify differentially expressed miRNAs (DEmiRs) comparing 11 tumoral tissues (TT) paired with non-neoplastic tissues (NNT) with further validation in an independent cohort ( = 13). We also investigated the mRNA expression of 83 genes in the total sample. Experimentally validated targets of DEmiRs, miRNA-mRNA networks, and enriched pathways were evaluated in silico. Eight out of 69 DEmiRs identified by microarray analysis were validated by qRT-PCR (miR-145-5p, miR-432-5p, miR-487b-3p, miR-30a-5p, miR-200a-5p, miR-224-5p, miR-31-3p and miR-31-5p). Furthermore, 37 differentially expressed genes (DEGs) were identified when comparing TT and NNT. We identified four downregulated DEmiRs (miR-30a-5p, miR-432-5p, miR-487b-3p, and miR-145-5p) and six upregulated DEGs (, , , , and ) as potential biomarkers in PeC by their capacity of discriminating TT and NNT with accuracy. The integration analysis showed eight dysregulated miRNA-mRNA pairs in penile carcinogenesis. Taken together, our findings contribute to a better understanding of the regulatory roles of miRNAs and altered transcripts levels in penile carcinogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13194745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507530PMC
September 2021

Behavioral factors associated with multiple-type HPV genital infections: data from a cross-sectional study in young women in Brazil.

Reprod Health 2021 Oct 10;18(1):201. Epub 2021 Oct 10.

Hospital Moinhos de Vento, Porto Alegre, Brazil.

Objectives: To investigate the pattern of multiple human papillomavirus (HPV) infections and associated factors in young women who access the Brazilian public health care system to better understand the characteristics of multiple HPV infections, a critical issue in this era of multivalent vaccines.

Methods: This was a cross-sectional, multicenter study with sexually active unvaccinated women (16-25 years old) from 119 primary Brazilian healthcare centers between September 2016 and November 2017. Cervical samples were collected by trained health professionals, and HPV detection was performed in a central laboratory by Linear Array.

Results: Of the 5268 women, 33.00% (95% CI 31.07-34.92) had multiple infections. At least one type of high-risk HPV was present in 85.50% of all multiple infections. All HPV types were detected more frequently in association with other types than alone. Young individuals who were single or in a casual relationship and those who had more than one sexual partner in the past year were more likely to have multiple infections.

Conclusions: In this work, a high rate of multiple HPV infections among unvaccinated young adults tended to increase due to certain risk factors. Such data can provide insight for decision makers in the development of public policies regarding HPV prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12978-021-01244-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504082PMC
October 2021

E6/E7 Functional Differences among Two Natural Human Papillomavirus 18 Variants in Human Keratinocytes.

Viruses 2021 06 10;13(6). Epub 2021 Jun 10.

Center for Translational Research in Oncology, Instituto do Cancer do Estado de São Paulo (ICESP), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), São Paulo 01246-000, Brazil.

It is suggested that HPV-18 variants from the A lineage have higher oncogenic potential compared to B variants. Some studies show uneven distribution of HPV-18 variants in cervical adenocarcinomas and squamous cell carcinomas. Regarding HPV-18 variants' functions, the few studies reported focus on E6, and none were performed using natural host cells. Here, we immortalized primary human keratinocytes (PHKs) with E6/E7 of HPV-18 A1 and B1 sublineages and functionally characterized these cells. PHK18A1 reached immortalization significantly faster than PHK18B1 and formed a higher number of colonies in monolayer and 3D cultures. Moreover, PHK18A1 showed greater invasion ability and higher resistance to apoptosis induced by actinomycin-D. Nevertheless, no differences were observed regarding morphology, proliferation after immortalization, migration, or epithelial development in raft cultures. Noteworthy, our study highlights qualitative differences among HPV-18 A1 and B1 immortalized PHKs: in contrast to PHK18A1, which formed more compact colonies and spheroids of firmly grouped cells and tended to invade and migrate as clustered cells, morphologically, PHK18B1 colonies and spheroids were looser, and migration and invasion of single cells were observed. Although these observations may be relevant for the association of these variants with cervical cancer of different histological subtypes, further studies are warranted to elucidate the mechanisms behind these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13061114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228617PMC
June 2021

Prevalence of oral HPV infection in unvaccinated young adults in Brazil.

Oral Oncol 2021 09 25;120:105396. Epub 2021 Jun 25.

Hospital Moinhos de Vento, Porto Alegre, Brazil; Department of Community Health, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil. Electronic address:

Objectives: This study aimed to report the national prevalence of oral HPV infection among unvaccinated women and men aged 16-25 years who utilized the public primary care services.

Methods: POP-Brazil is a cross-sectional, multicentric, nationwide survey conducted between September 2016 and November 2017. Recruitment was based in 119 public primary care practices in 26 state capitals and the Federal District of Brazil. Trained health professionals conducted face-to-face interviews. Oral samples were collected with mouthwash and gargle cycles. Genotyping was performed using the Roche PCR-based linear array genotyping test. Sampling weights by sex and age were applied.

Results: Valid oral HPV samples were collected from 5071 (96.88%) participants; 4005 women and 1066 men. Mean participant age was 21.63 years. Overall HPV prevalence was 1.69% (n = 73, 95% CI 1.05-2.32). Thirty individuals presented at least one high-risk HPV type [0.57% (95% CI, 0.29-0.85)]. There were no associations between age, sex, sociodemographic characteristics, drug use or sexual behavior and oral HPV prevalence.

Conclusion: The prevalence of oral HPV infection in Brazilian teenagers and young adults is low, with no sociodemographic or behavioral correlates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oraloncology.2021.105396DOI Listing
September 2021

Dysregulation of Transcription Factor Networks Unveils Different Pathways in Human Papillomavirus 16-Positive Squamous Cell Carcinoma and Adenocarcinoma of the Uterine Cervix.

Front Oncol 2021 19;11:626187. Epub 2021 May 19.

Instituto Carlos Chagas, FIOCRUZ, Curitiba, Brazil.

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are the most common histological types of cervical cancer (CC). The worse prognosis of ADC cases highlights the need for better molecular characterization regarding differences between these CC types. RNA-Seq analysis of seven SCC and three ADC human papillomavirus 16-positive samples and the comparison with public data from non-tumoral human papillomavirus-negative cervical tissue samples revealed pathways exclusive to each histological type, such as the epithelial maintenance in SCC and the maturity-onset diabetes of the young (MODY) pathway in ADC. The transcriptional regulatory network analysis of cervical SCC samples unveiled a set of six transcription factor (TF) genes with the potential to positively regulate long non-coding RNA genes , and . Additional analysis revealed a set of MODY TFs regulated in the sequence predicted to be repressed by miR-96-5p or miR-28-3p in ADC. These microRNAs were previously described to target LINC02381, which was predicted to be positively regulated by two MODY TFs upregulated in cervical ADC. Therefore, we hypothesize might act by decreasing the levels of miR-96-5p and miR-28-3p, promoting the MODY activation in cervical ADC. The novel TF networks here described should be explored for the development of more efficient diagnostic tools.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.626187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170088PMC
May 2021

Low RECK Expression Is Part of the Cervical Carcinogenesis Mechanisms.

Cancers (Basel) 2021 May 6;13(9). Epub 2021 May 6.

Laboratory of Oncovirology, Department of Microbiology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-900, Brazil.

Human papillomavirus (HPV)-induced carcinogenesis comprises alterations in the expression and activity of matrix metalloproteinases (MMP) and their regulators. Reversion-inducing Cysteine-rich protein with Kazal motifs (RECK) inhibits the activation of specific metalloproteinases and its expression is frequently lost in human cancers. Here we analyzed the role of RECK in cervical carcinogenesis. Cervical cancer derived cell lines over expressing RECK were used to determine tumor kinetics as well as, cellular, immune and molecular properties in vivo. Besides, we analyzed RECK expression in cervical cancer samples. RECK over expression (RECK+) delayed tumor growth and increased overall survival in vivo. RECK+ tumors displayed an increase in lymphoid-like inflammatory infiltrating cells, reduced number and viability of tumor and endothelial cells and lower collagenase activity. RECK+ tumors exhibited an enrichment of cell adhesion processes both in the mouse model and cervical cancer clinical samples. Finally, we found that lower RECK mRNA levels were associated with cervical lesions progression and worse response to chemotherapy in cervical cancer patients. Altogether, we show that increased RECK expression reduced the tumorigenic potential of HPV-transformed cells both in vitro and in vivo, and that RECK down regulation is a consistent and clinically relevant event in the natural history of cervical cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13092217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124470PMC
May 2021

Effectiveness of a universal vaccination program with an HPV quadrivalent vaccine in young Brazilian women.

Vaccine 2021 03 2;39(13):1840-1845. Epub 2021 Mar 2.

Department of Chronic Conditions and Sexually Transmitted Infections, Brasília, Distrito Federal, Brazil.

We examined human papillomavirus (HPV) vaccine effectiveness in a nationwide sample of women aged 16 to 25 years who utilized the public health system in Brazil. This was a cross-sectional, multicentric survey conducted between September 2016 and November 2017 (POP-Brazil Study). A total of 5,945 young adult women were recruited from 119 public primary care units from all 27 federative units of Brazil by trained health professionals. The participants participated in a face-to-face interview and provided biological samples for genital HPV analysis. HPV genotyping was performed using a Linear Array HPV genotyping test in a central laboratory. Sampling weights were applied to the data. Overall, 11.92% (95% CI 10.65, 13.20) of the participants reported having been vaccinated. The frequency of vaccination was highest in 16- to 17-year-old women, with a decreasing vaccination rate with increasing age, and vaccinated women were more likely to belong to the high socioeconomic status group. The use of a quadrivalent vaccine decreased the HPV types 6, 11, 16, and 18 by 56.78%, from 15.64% in unvaccinated women to 6.76% in vaccinated women (P < 0.01), even after adjustment for age. Those who received the vaccine had lower HPV 16 (2.34% in vaccinated vs 8.91% in unvaccinated, P < 0.01) and 6 rates (2.06% vs 5.77%, P < 0.01). Additionally, a higher rate of high-risk HPV types other than HPV 16 and 18 (40.47% in vaccinated vs 32.63% in unvaccinated, P < 0.01) was observed. In conclusion, the results of this study support the effectiveness of HPV vaccination in Brazil. Continuous surveillance must be assured to monitor the HPV infection rate in the vaccination era.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2021.02.040DOI Listing
March 2021

Global incidence trends in head and neck cancer for HPV-related and -unrelated subsites: A systematic review of population-based studies.

Oral Oncol 2021 04 6;115:105177. Epub 2021 Feb 6.

Department of Epidemiology, School of Public Health, University of São Paulo, São Paulo, Brazil.

In head and neck cancer (HNC), some subsites are associated with human papillomavirus (HPV) infection, whereas others are unrelated. Although studies have demonstrated the heterogeneity of HPV prevalence worldwide, its impacts on incidence trends in HNC are unknown. This systematic review examined the incidence trends for HPV-related HNC subsites, exploring patterns by geographic region, age group, sex, and race/ethnicity. We searched for publications on PubMed, Embase, and Scopus. Eligible articles included population-based studies that analyzed incidence trends for subsites classified as a proxy for HPV infection in HNC (hereafter referred to as HPV-related subsites). We retrieved 3,948 non-duplicate records, of which 31 were eligible articles, representing 18 countries and spanning almost fifty years. Overall, the incidence of HPV-related HNC subsites rose, while most of the HPV-unrelated subsites declined or remained stable. For HPV-related HNC subsites, incidence trends increased regardless of age group, highlighting a distinct global pattern between sexes. Also, similar peaks in increased risk were observed in recent cohorts from both Australia and the United States. There is a dramatic shift in the global trends of HNCs, characterized by the emerging burden in HNC for HPV-related subsites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oraloncology.2020.105177DOI Listing
April 2021

Sex differences in the prevalence and determinants of HPV-related external genital lesions in young adults: a national cross-sectional survey in Brazil.

BMC Infect Dis 2020 Sep 18;20(1):683. Epub 2020 Sep 18.

Hospital Moinhos de Vento, PROADI - SUS, Ramiro Barcelos, 910, Porto Alegre, RS, 90035-004, Brazil.

Background: External genital lesions (EGL) are the most common sexually transmitted infections (STIs). We aimed to evaluate the prevalence, determinants and sex differences in EGL among young adults from Brazil.

Methods: Overall, 7694 participants (aged 16 to 25 years) underwent an interview, genital examination and sampling for HPV genotyping.

Results: The prevalence of EGL was 4.08% (234) and is more frequent in men (5.72%) than women (2.31%) (p <  0.001). Genital lesions were significantly associated with male sex, infection by high-risk and multiple HPV types, having more than two sexual partners in the last year, smoking status and the presence of other STI. While alcohol use was associated with a higher prevalence of EGL in women, same-sex sexual relationship increase the prevalence in men. In the EGL group, 67.79% (p = 0.032) were positive for HPV infection and the types HPV6 and HPV11 were the most prevalent ones.

Conclusion: The prevalence of EGL in young adults was consistently high, and most cases were associated with genital HPV infection and STIs. Although men have a higher prevalence, both sexes share most genital lesion determinants. The promotion of sexual education and vaccination especially focus in young men, who are usually outside the targets of primary health care programmes, can prevent EGL in Brazilian young adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-020-05376-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501703PMC
September 2020

High p16 immunoexpression is not HPV dependent in oral leukoplakia.

Arch Oral Biol 2020 Jul 4;115:104738. Epub 2020 May 4.

Oral Oncology Center, São Paulo State University (UNESP), School of Dentistry, Araçatuba, Brazil; Department of Diagnosis and Surgery, São Paulo State University (UNESP), School of Dentistry, Araçatuba, Brazil. Electronic address:

Objective: To evaluate the prevalence of HPV DNA detection in fresh tissue from oral leukoplakia by Linear Array assay, and its correlation with p16 immunoexpression in the northwest region of the São Paulo state, Brazil.

Patients And Methods: Fifty patients diagnosed with oral leukoplakia were included in the study. Sociodemographic, clinicopathologic and lifestyle data, fresh tissue and formalin fixed paraffin embedded (FFPE) tissue samples were collected. The fresh tissue was stored at -80 °C and then submitted to further viral DNA detection by the Linear Array method. Immunohistochemical analysis for the p16 expression was performed.

Results: Of the 50 patients included in the study, 62 % were men, and the age ranged from 25 to 82 years. Twenty-three (46 %) were elderly, 46 % were middle-aged adults, and only 12 % were young adults. Most patients were smokers (76 %), 14 % were former smokers, and 10 % were non-smokers. Most patients (56 %) were current drinkers, 22 % were ex-drinkers and 22 % were non-drinkers. Thirty-two percent of the lesions presented some degree of dysplasia. No lesions were positive to HPV by Linear Array detection. Thirty (60 %) OL had p16-low immunoexpression and 20 (40 %) had p16-high immunoexpression.

Conclusion: HPV was not identified in the population studied. The high p16 immunoexpression is not dependent on HPV in oral leukoplakia. Broader epidemiological studies are required to clarify the geographic variability in the prevalence of HPV in head and neck squamous cell carcinoma and oral potentially malignant lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.archoralbio.2020.104738DOI Listing
July 2020

Prevalence of HPV infection among sexually active adolescents and young adults in Brazil: The POP-Brazil Study.

Sci Rep 2020 03 18;10(1):4920. Epub 2020 Mar 18.

Tropical Medicine Foundation Heitor Vieira Dourado and Global Aids Healthcare Foundation, Manaus, Brazil.

For Brazil, there are no nationwide data on HPV prevalence against which the impact of the HPV immunization program can be measured in the future. Therefore, we aim to evaluate the prevalence of genital HPV infection among adolescents and young adults in Brazil. A cross-sectional, multicentric, nationwide survey was conducted between September 2016 and November 2017. Sexually active unvaccinated women and men aged 16 to 25 years old were recruited from 119 public primary care units, including all 26 state capitals and the Federal District. All participants answered a face-to-face interview and provided biological samples for genital HPV analysis. We used an automated DNA extraction method and HPV genotyping was performed using the Linear Array genotyping test (Roche). Of 7,694 participants, 53.6% (95% CI 51.4-55.8) were positive for any HPV type. The prevalence of high-risk HPV types was significantly higher in women (38.6% vs. 29.2%, P < 0·001). The HPV types included in the quadrivalent vaccine were detected in 1002 (14.8%) specimens, with a different pattern of HPV infection between sexes. Characteristics associated with overall HPV detection included female gender, self-declaration of race as brown/pardo, lower socioeconomic class, single or dating, current smoking and having 2 or more sex partners in the past year. We found a high prevalence of HPV, with significant differences between regions. Our data provide information that may be considered when developing HPV prevention policies and constitute a baseline against which the impact of the HPV immunization program in Brazil can be measured in future years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-61582-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080737PMC
March 2020

Antiviral activity of curcumin-nanoemulsion associated with photodynamic therapy in vulvar cell lines transducing different variants of HPV-16.

Artif Cells Nanomed Biotechnol 2020 Dec;48(1):515-524

Laboratory of Genomic Studies, Sao Paulo State University - UNESP, São Paulo, Brazil.

Vulvar intraepithelial neoplasia (VIN) is associated with human papillomavirus (HPV) infection. Curcumin is a natural bioactive compound with antineoplastic properties. The use of nanoparticles containing curcumin could allow a better performance of this compound in therapies. So, VIN biopsies were collected and HPV DNA detection was performed by PCR, positive samples were genotyped by Restriction Fragment Length Polymorphism (RFLP) and HPV-16 variants were determined by sequencing. HPV-16 positive vulva carcinoma cells (A431) were transduced with E-P and E-350G HPV-16 E6 variants. The viability of the transduced cells treated with nanoemulsions was determined by MTT assay. Besides, apoptosis was evaluated by enzymatic activity of Caspase-3/7. The cell viability assay showed that both the empty nanoemulsion (NE-V) and the nanoemulsion of curcumin (NE-CUR) had little effect on cell viability as compared to control cells. Additionally, we observed that cells irradiated in the presence of NE-CUR presented 90% of cell death. The apoptosis assay further revealed a significant increase in the activity of caspases 3 and 7 in A431 cells expressing both HPV-16 E6 variants after treatment with NE-CUR. Finally, we submitted the HPV transduced A431 cells to organotypic cultures and observed that the combination of treatments affected tissue architecture with evident signals of tissue damage. We concluded that nanoemulsions attain good biocompatibility, since no cytotoxicity was observed and NE-CUR associated with photoactivation showed promising results, leading to death only in cells subjected to irradiation. This drug delivery system associated with photodynamic therapy may become promising in the treatment of vulva lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21691401.2020.1725023DOI Listing
December 2020

Role of epstein-barr virus in the severity of recurrent respiratory papillomatosis.

Laryngoscope 2020 11 20;130(11):E611-E618. Epub 2019 Dec 20.

Center for Translational Investigation in Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Objective: The objective was to investigate the prevalence of the Epstein-Barr virus (EBV) and its association with human papilloma virus (HPV) detection, clinicopathological features, and the severity of recurrent respiratory papillomatosis (RRP).

Methods: Cases of juvenile recurrent respiratory papillomatosis (JRRP) (n = 36) and adult recurrent respiratory papillomatosis (ARRP) (n = 44) were collected retrospectively and subdivided into low- and high-risk severity groups based on the Derkay score. We performed HPV detection and genotyping using a reverse hybridization protocol and investigated the presence of EBV by polymerase chain reaction (PCR) and in situ hybridization. CD21 levels were accessed by immunohistochemistry.

Results: All samples were HPV-positive, including 49 cases of HPV 6, 26 cases of HPV 11, four cases of HPV 6 and 11 coinfections, and one case of HPV 16. EBV-DNA was detected in nine samples by PCR, although none of the cases were positive by means of in situ hybridization. CD21 immunoexpression was not statistically associated with any of the variables analyzed. HPV 6 detection was significantly higher in ARRP cases (P = 0.03), whereas HPV 11 was more prevalent in JRRP cases (P = 0.02) and was even more prevalent in JRRP cases of greater severity (Derkay laryngoscopic scale ≥20) (P = 0.04).

Conclusion: The presence of EBV does not seem to play an important role in the progression/severity of RRP.

Level Of Evidence: 4 Laryngoscope, 130:E611-E618, 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.28465DOI Listing
November 2020

Human Papillomavirus and Anal Cancer: Prevalence, Genotype Distribution, and Prognosis Aspects from Midwestern Region of Brazil.

J Oncol 2019 18;2019:6018269. Epub 2019 Sep 18.

Universidade Federal de Goiás, Postgraduate Program in Health Sciences, Faculty of Medicine, Goiânia, Goiás, CEP 74605-020, Brazil.

Background: Approximately 90% of all anal cancers are associated with human papillomavirus (HPV), especially high-risk genotypes such as HPVs 16 and 18.

Objective: To investigate the clinical and prognostic aspects of anal cancers associated with the presence, as well as the genotypic distribution of human papillomavirus (HPV).

Methods: A retrospective study carried out over a 10-year period, using clinical and molecular data, with PCR analysis and reverse hybridization (INNO-LIPA kit), in anal cancers. The data analysis was done using descriptive univariate statistics, and the survival curves were made using the Kaplan-Meier and log-rank methods.

Results: Of the 81 formalin-fixed and paraffin-embedded specimens, HPV prevalence was 69% and was significantly higher in squamous cell carcinomas (SCC) than in other anal tumors (=0.0001). Female patients had a higher prevalence of HPV (=0.01). Multiple infections were detected in 14.3% of cases. The most prevalent genotypes were HPVs 16, 33, and 18. The overall survival at 60 months was 44.3%, and the prognostic factors included gender (=0.008) with greater survival for men (52.9%) in comparison to women (29.6%), histological type (=0.01), SCC (54.4%), adenocarcinomas (37.5%), other carcinomas (14.2%), and the presence of distant metastasis (=0.01). Survival was not influenced by the presence of HPV (=0.54).

Conclusions: The association of HPV to anal cancer was found in this study, especially in SCC. However, the presence of HPV did not influence the prognosis of patients with anal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/6018269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766672PMC
September 2019

Diversity of human papillomavirus typing among women population living in rural and remote areas of Brazilian territory.

Papillomavirus Res 2019 12 17;8:100186. Epub 2019 Sep 17.

Teaching and Research Institute, Molecular Oncology Research Center, Barretos Cancer Hospital, Pio XII Foundation, Brazil; Medical Laboratory of Medical Investigation (LIM) 14. Department of Pathology, Faculty of Medicine, Universidade de São Paulo, Brazil; Research Institute of Life and Health Sciences (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS / 3B's - Associated Laboratory to the Government of Portugal, Braga, Guimarães, Portugal. Electronic address: http://www.icvs.uminho.pt.

Objectives: Genotyping HPV from samples tested positive to careHPV™ assay in rural and remote areas of Brazilian territory.

Methods: A total of 5079 women were enrolled in an opportunistic screening from the Barretos Cancer Hospital, through mobile units or ambulatory unit. All careHPV™ hr-HPV positive samples were tested by a Luminex-based protocol in order to evaluate the HPV infecting types.

Results: Positive hr-HPV results were obtained in 10.6% (536/5068) of women. Among these cases, HPV-56 and HPV-51 were the most common types detected in 32.3% and 31.4%, respectively. HPV-53 (20.5%), HPV-18 (18.5%), HPV-58 (17.6%), HPV-52 (16.0%) and HPV-16.6%) were the other most frequent types detected. These frequencies represent prevalences of 2.35%, 2.12%, 2.02%, 1.84% and 1.80% respectively, within the population studied. Regarding low-risk HPVs, HPV-6 was detected in 12.9% of the samples. The less frequent types (<3%) were: HPV-70, HPV-11 and HPV-26.

Conclusions: The most frequent types detected were: HPV-56, HPV-51, HPV-53, HPV-18, HPV-58, HPV-52 and HPV-16 according to decreasing rates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pvr.2019.100186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804508PMC
December 2019

Indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase expression in HPV infection, SILs, and cervical cancer.

Cancer Cytopathol 2019 09 14;127(9):586-597. Epub 2019 Aug 14.

Department of Clinical Analysis and Toxicology, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.

Background: Human papillomavirus (HPV) infection is the central factor for cervical cancer, whereas epithelial immune mechanisms contribute to the progression of HPV infection and its associated lesions. The authors evaluated the expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) in cervicovaginal samples from women with normal cervical epithelium or with different degrees of squamous intraepithelial lesions (SILs) and cervical cancer.

Methods: IDO expression was analyzed by immunocytochemistry in liquid-based cytology samples from 165 women, of whom 42 had cervical changes subclassified as low-grade SIL (n = 6), high-grade SIL (n = 30), or squamous cell carcinoma (SCC) (n = 6), and 123 had negative Papanicolaou smears. IDO and TDO expression also were analyzed by immunohistochemistry, and HPV and other genital pathogens were evaluated by polymerase chain reaction analysis.

Results: Low IDO expression was observed in normal cervical epithelium irrespective of HPV status. Increased numbers of IDO-positive squamous cells and IDO-positive leukocytes were observed in women with SIL or SCC. TDO expression was detected in leukocytes infiltrating the stroma around intraepithelial or invasive cervical lesions. Higher IDO levels were detected in organotypic epithelial cultures established from keratinocytes transduced with the HPV16 E6/E7 oncoproteins.

Conclusions: The upregulation of IDO expression in leukocytes and squamous cells in HPV-associated SIL and SCC suggests that immunosuppressive mechanisms involving tryptophan metabolism may have a role in cervical carcinogenesis. Although previous studies have suggested the role of IDO in HPV pathogenesis, this is the first evidence of TDO involvement in the process. Furthermore, the current data emphasize the role of leukocytes, especially neutrophil-like cells, as an IDO source.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncy.22172DOI Listing
September 2019

Human papillomavirus is not associated to non-small cell lung cancer: data from a prospective cross-sectional study.

Infect Agent Cancer 2019 2;14:18. Epub 2019 Aug 2.

1Teaching and Research Institute, Molecular Oncology Research Center, Barretos Cancer Hospital - Pio XII Foundation, Barretos, Brazil.

Background: The pathogenesis of lung cancer is triggered by a combination of genetic and environmental factors, being the tobacco smoke the most important risk factor. Nevertheless, the incidence of lung cancer in non-smokers is gradually increasing, which demands the search for different other etiological factors such as occupational exposure, previous lung disease, diet among others. In the early 80's a theory linked specific types of human papillomavirus (HPV) to lung cancer due to morphological similarities of a subset of bronchial squamous cell carcinomas with other HPV-induced cancers. Since then, several studies revealed variable rates of HPV DNA detection. The current study aimed to provide accurate information on the prevalence of HPV DNA in lung cancer.

Methods: Biopsies were collected from 77 newly diagnosed non-small cell lung cancer (NSCLC) patients treated at the Thoracic Oncology Department at Barretos Cancer Hospital. The samples were formalin fixed and paraffin embedded (FFPE), histologic analysis was performed by an experienced pathologist. DNA was extracted from FFPE material using a commercial extraction kit and HPV DNA detection was evaluated by multiplex PCR and HPV16 specific real-time PCR.

Results: HPV was not identified in any of the samples analysed (69).

Conclusions: Our data demonstrated a lack of HPV DNA in a series of NSCL cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13027-019-0235-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679449PMC
August 2019

Factors associated with HPV and other self-reported STI coinfections among sexually active Brazilian young adults: cross-sectional nationwide study.

BMJ Open 2019 06 21;9(6):e027438. Epub 2019 Jun 21.

Escritório de Projetos PROADI-SUS, Hospital Moinhos de Vento, Porto Alegre, Rio Grande do Sul, Brazil.

Objectives: To analyse factors associated with genital human papillomavirus (HPV) and other self-reported sexually transmitted infection (STI) coinfections among women and men aged 16-25 years from Brazil.

Design: A cross-sectional, nationwide, multicentre study.

Setting: 119 primary healthcare centres between September 2016 and November 2017.

Participants: 6388 sexually active young adults were enrolled by trained health professionals.

Primary Outcome Measure: Genital HPV and other self-reported STI coinfections.

Results: Of 3512 participants with valid data for genital HPV and (STI)-positive status, 276 (9.60%, 95% CI 7.82% to 11.36%) had HPV/STI coinfection. Among men, HPV/STI coinfection was more prevalent than HPV infection alone. Among HPV-positive participants, the percentage of subjects who reported having another STI was highest for gonorrhoea at 4.24% (95% CI 2.67% to 5.81%), followed by syphilis, herpes and HIV. Smoking, drug use and ever having a same-sex sexual experience were risk factors that were uniquely associated with HPV/STI coinfection compared with HPV infection alone.

Conclusions: The results identified a low prevalence of self-reported STIs, but in participants with at least one STI, the prevalence of HPV was high. These results reinforce the importance of implementing strategies to prevent risky behaviours among Brazilian young adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2018-027438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596954PMC
June 2019

HPV Vaccine: Updates and Highlights.

Acta Cytol 2019 14;63(2):159-168. Epub 2019 Mar 14.

Faculdade de Medicina, Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo (SP), Brazil.

HPV is the most common sexually transmitted biological agent and is the cause of many conditions in men and women, including precancer lesions and cancer. Three prophylactic HPV vaccines targeting high-risk HPV types are available in many countries worldwide: 2-, 4- and 9-valent vaccines. All the 3 vaccines use recombinant DNA technology and are prepared from the purified L1 protein that self-assembles to form HPV type-specific empty shells. This non-systematic review aims to summarize the HPV epidemiology and the vaccine development to review the landmark trials of HPV vaccine, to present to most remarkable results from clinical trials and the real world, and to stress the challenges and the barriers for HPV vaccine implementation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000497617DOI Listing
May 2019

Swainsonine, an alpha-mannosidase inhibitor, may worsen cervical cancer progression through the increase in myeloid derived suppressor cells population.

PLoS One 2019 6;14(3):e0213184. Epub 2019 Mar 6.

Instituto de Ciências Biomédicas, Universidade de São Paulo, Departamento de Imunologia, São Paulo, Brazil.

Cervical cancer, caused by high oncogenic risk Human Papillomavirus (HPV) infection, continues to be a public health problem, mainly in developing countries. Using peptide phage display as a tool to identify potential molecular targets in HPV associated tumors, we identified α-mannosidase, among other enriched sequences. This enzyme is expressed in both tumor and inflammatory compartment of the tumor microenvironment. Several studies in experimental models have shown that its inhibition by swainsonine (SW) led to inhibition of tumor growth and metastasis directly and indirectly, through activation of macrophages and NK cells, promoting anti-tumor activity. Therefore, the aim of this work was to test if swainsonine treatment could modulate anti-tumor immune responses and therefore interfere in HPV associated tumor growth. Validation of our biopanning results showed that cervical tumors, both tumor cells and leukocytes, expressed α-mannosidase. Ex vivo experiments with tumor associated macrophages showed that SW could partially modulate macrophage phenotype, decreasing CCL2 secretion and impairing IL-10 and IL-6 upregulation, which prompted us to proceed to in vivo tests. However, in vivo, SW treatment increased tumor growth. Investigation of the mechanisms leading to this result showed that SW treatment significantly induced the accumulation of myeloid derived suppressor cells in the spleen of tumor bearing mice, which inhibited T cell activation. Our results suggested that SW contributes to cervical cancer progression by favoring proliferation and accumulation of myeloid cells in the spleen, thus exacerbating these tumors systemic effects on the immune system, therefore facilitating tumor growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213184PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402676PMC
December 2019

Human Papillomavirus and Genital Disease in Men: What We Have Learned from the HIM Study.

Acta Cytol 2019 22;63(2):109-117. Epub 2019 Feb 22.

Center for Translational Research in Oncology, Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, Brazil,

It is currently recognized that in addition to the major impact of human papillomavirus (HPV) infection in females, HPV causes considerable disease in men at the genitals, anal canal, and oropharynx. Specifically, genital HPV infections may progress to genital warts and penile carcinoma. Although studies concerning the natural history of HPV infections and associated neoplasias have mainly focused on women, during the last 2 decades considerable attention has been given in further understanding these infections in men. The HIM (HPV infection in men) Study, the only prospective multicenter study of male HPV natural history, consisted of a large prospective international cohort study in which men from Brazil, the United States, and Mexico were enrolled. The design and protocols of this study allowed unraveling crucial information regarding the relationship between HPV infection and clinical consequences in men, and associated risk factors at each of the anatomic sites where HPV is known to cause cancer in men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000493737DOI Listing
May 2019

HPV-Mediated Resistance to TNF and TRAIL Is Characterized by Global Alterations in Apoptosis Regulatory Factors, Dysregulation of Death Receptors, and Induction of ROS/RNS.

Int J Mol Sci 2019 Jan 8;20(1). Epub 2019 Jan 8.

Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, Brazil.

Persistent infection with high-risk human papilloma virus (HR-HPV) is the main risk factor for the development of invasive cervical cancer although is not sufficient to cause cervical cancer. Several host and environmental factors play a key role in cancer initiation/progression, including cytokines and other immune-response mediators. Here, we characterized the response to the individual and combined action of the pro-inflammatory cytokines tumor necrosis factor (TNF) and TNF-related apoptosis-inducing ligand (TRAIL) on HPV-transformed cells and human keratinocytes ectopically expressing E6 and E7 early proteins from different HPV types. We showed that keratinocytes expressing HPV early proteins exhibited global alterations in the expression of proteins involved in apoptosis regulation/execution, including TNF and TRAIL receptors. Besides, we provided evidence that TNF receptor 1 (TNFR1) was down-regulated and may be retained in the cytoplasm of keratinocytes expressing HPV16 oncoproteins. Finally, fluorescence analysis demonstrated that cytokine treatment induced the production and release of reactive oxygen and nitrogen species (ROS/RNS) in cells expressing HPV oncogenes. Alterations in ROS/RNS production and apoptosis regulatory factors expression in response to inflammatory mediators may favor the accumulation of genetic alterations in HPV-infected cells. Altogether, our results suggested that these events may contribute to lesion progression and cancer onset.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20010198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337392PMC
January 2019

Innate immunity and HPV: friends or foes.

Clinics (Sao Paulo) 2018 10 11;73(suppl 1):e549s. Epub 2018 Oct 11.

Centro de Investigacao Translacional em Oncologia, Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, BR.

Most human papillomavirus infections are readily cleared by the host immune response. However, in some individuals, human papillomavirus can establish a persistent infection. The persistence of high-risk human papillomavirus infection is the major risk factor for cervical cancer development. These viruses have developed mechanisms to evade the host immune system, which is an important step in persistence and, ultimately, in tumor development. Several cell types, receptors, transcription factors and inflammatory mediators involved in the antiviral immune response are viral targets and contribute to tumorigenesis. These targets include antigen-presenting cells, macrophages, natural killer cells, Toll-like receptors, nuclear factor kappa B and several cytokines and chemokines, such as interleukins, interferon and tumor necrosis factor. In the present review, we address both the main innate immune response mechanisms involved in HPV infection clearance and the viral strategies that promote viral persistence and may contribute to cancer development. Finally, we discuss the possibility of exploiting this knowledge to develop effective therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6061/clinics/2018/e549sDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157093PMC
October 2018

Juvenile-onset recurrent respiratory papillomatosis with pulmonary involvement and carcinomatous transformation.

Autops Case Rep 2018 Jul-Sep;8(3):e2018035. Epub 2018 Jul 30.

Santa Casa de São Paulo School of Medical Sciences, School of Medicine. São Paulo, SP, Brazil.

Papilloma associated with recurrent respiratory papillomatosis (RRP), caused by human papilloma virus (HPV) infection types 6 and 11, is the most common benign neoplasm of the larynx. The clinical features of RRP vary widely from mild to aggressive forms. RRP in children is known as juvenile-onset recurrent respiratory papillomatosis (JORRP). Its outcome may be poor or even fatal due to the high rate of recurrence and eventual spread to the entire respiratory tract. Pulmonary invasion is reported to occur in 3.3% of patients with RRP, and malignant transformation in 0.5% of patients. We report the case of a 39-year-old female patient with a diagnosis of JORRP from the age of 3 years, with extensive bilateral pulmonary involvement and malignant transformation. Analysis of the papilloma and carcinomatous tissues revealed the presence of HPV type 11, which is associated with rapid and aggressive progression. We discussed the case on the basis of a literature review on pulmonary invasion, malignant transformation, and HPV 11 aggressiveness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4322/acr.2018.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066261PMC
July 2018

B lymphocytes can be activated to act as antigen presenting cells to promote anti-tumor responses.

PLoS One 2018 5;13(7):e0199034. Epub 2018 Jul 5.

Department of Immunology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.

Immune evasion by tumors includes several different mechanisms, including the inefficiency of antigen presenting cells (APCs) to trigger anti-tumor T cell responses. B lymphocytes may display a pro-tumoral role but can also be modulated to function as antigen presenting cells to T lymphocytes, capable of triggering anti-cancer immune responses. While dendritic cells, DCs, are the best APC population to activate naive T cells, DCs or their precursors, monocytes, are frequently modulated by tumors, displaying a tolerogenic phenotype in cancer patients. In patients with cervical cancer, we observed that monocyte derived DCs are tolerogenic, inhibiting allogeneic T cell activation compared to the same population obtained from patients with precursor lesions or cervicitis. In this work, we show that B lymphocytes from cervical cancer patients respond to treatment with sCD40L and IL-4 by increasing the CD80+CD86+ population, therefore potentially increasing their ability to activate T cells. To test if B lymphocytes could actually trigger anti-tumor T cell responses, we designed an experimental model where we harvested T and B lymphocytes, or dendritic cells, from tumor bearing donors, and after APC stimulation, transplanted them, together with T cells into RAG1-/- recipients, previously injected with tumor cells. We were able to show that anti-CD40 activated B lymphocytes could trigger secondary T cell responses, dependent on MHC-II expression. Moreover, we showed that dendritic cells were resistant to the anti-CD40 treatment and unable to stimulate anti-tumor responses. In summary, our results suggest that B lymphocytes may be used as a tool for immunotherapy against cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199034PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033398PMC
December 2018

Methylation of the hsa-miR-124, SOX1, TERT, and LMX1A genes as biomarkers for precursor lesions in cervical cancer.

Gynecol Oncol 2018 09 28;150(3):545-551. Epub 2018 Jun 28.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil; A.C. Camargo Cancer Center, São Paulo, Brazil. Electronic address:

Objectives: The methylation profile of genes in precursor lesions in cervical cancer was characterized to improve screening techniques for high-grade intraepithelial neoplasia.

Methods: A total of 447 cervical cytology samples obtained from women who underwent colposcopy were examined. The cases were distributed as follows: (1) cervices without cervical intraepithelial neoplasia (CIN; n = 152); (2) cervices with a CIN grade of 1 (CIN 1; n = 147); and (3) cervices with a CIN grade of 2 or 3 (CIN 2/3; n = 148). The methylation pattern for a panel of 15 genes was analysed by quantitative methylation-specific PCR (qMSP) and compared between the groups (≤CIN 1 vs. CIN 2+).

Results: In the validation set, seven genes presented significantly different methylation profiles according to diagnosis, namely, DAPK1 (p = 0.001), EPB41L3 (p = 0.001), HIC1 (p = 0.028), hsa-miR-124-2 (p = 0.001), LMX1A (p = 0.001), SOX1 (p = 0.001), and TERT (p = 0.001). Six genes showed a significant increase in the frequency of methylation in the presence of hr-HPV, namely, DAPK1 (p = 0.001), EPB41L3 (p = 0.001), hsa-miR-124-2 (p = 0.001), LMX1A (p = 0.001), SOX1 (p = 0.001), and TERT (p = 0.001). The methylation of the hsa-miR-124 gene showed sensitivity and specificity (86.7% and 61.3%, respectively) similar to that of the HPV test (91.3% and 50.0%, respectively). The independent factors associated with the diagnosis of CIN 2+ and the methylation of the hsa-miR-124-2 (OR = 5.1), SOX1 (OR = 2.8), TERT (OR = 2.2), and LMX1A (OR = 2.0) genes were a positive test for hr-HPV (odds ratio [OR] = 5.5).

Conclusions: Hypermethylation of the hsa-miR-124-2, SOX1, TERT, and LMX1A genes may be a promising biomarker for precursor lesions in cervical cancer regardless of the hr-HPV status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2018.06.014DOI Listing
September 2018

POP-Brazil study protocol: a nationwide cross-sectional evaluation of the prevalence and genotype distribution of human papillomavirus (HPV) in Brazil.

BMJ Open 2018 06 7;8(6):e021170. Epub 2018 Jun 7.

Department of Surveillance, Prevention and Control of Sexually Transmitted Infections, HIV/AIDS and Viral Hepatitis, Brazilian Ministry of Health, Brasília, Brazil.

Introduction: Human papillomavirus (HPV) is associated with the development of genital warts and different types of cancer, including virtually all cervical cancers and a considerable number of penile, anal and oropharyngeal cancers. Data regarding the prevalence of HPV infection in Brazil are limited and fragmented. We aim to determine HPV prevalence in sexually active women and men aged 16-25 years and to investigate regional differences in virus prevalence and types.

Methods And Analysis: This is a nationwide, multicentric, cross-sectional, prospective study that will include participants aged 16-25 years from all Brazilian capital cities. Recruitment will occur in primary health units by trained health professionals who will be responsible for collecting biological samples and interviewing the volunteers. After signing informed consent, all participants will answer a questionnaire that will collect sociodemographic and behavioural data. All samples will be processed in a certified central laboratory, and strict quality control will be performed by many different procedures, including double data entry, training and certification of primary care health professionals responsible for data collection, simulation of interviews, and auditing and monitoring of visits. The sample size will be standardised based on the population distribution of each capital using SAS and R statistical software.

Ethics And Dissemination: The project was approved by the research ethics committee of the main institution and the corresponding ethics committees of the recruitment sites. This will be the first Brazilian nationwide study to determine overall HPV prevalence and to examine regional differences and social, demographic and behavioural factors related to HPV infection. Critical analysis of the study results will contribute to epidemiological knowledge and will set a baseline for future evaluation of the impact of the National HPV Vaccination Program.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2017-021170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009568PMC
June 2018
-->