LUISA LINA VILLA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Radiologia, Faculdade de Medicina - Docente
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
12 resultados
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- Frequency of Human Papillomavirus Detection in Chagasic Megaesophagus Associated or Not with Esophageal Squamous Cell Carcinoma(2022) MUNARI, F. F.; SICHERO, L.; CARLONI, A. C.; LACERDA, C. F.; NUNES, E. M.; OLIVEIRA, A. T. T. De; SCAPULATEMPO-NETO, C.; SILVA, S. R. M. Da; CREMA, E.; ADAD, S. J.; RODRIGUES, M. A. M.; HENRY, M. A. C. A.; GUIMARãES, D. P.; REIS, R. M.; VILLA, L. L.; LONGATTO-FILHO, A.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.
- HPV vaccination programs in LMIC: is it time to optimize schedules and recommendations?(2023) VILLA, Luisa Lina; RICHTMANN, RosanaObjectives: Prophylactic HPV vaccines are a fundamental tool to reduce infections and tumors caused by the most prevalent types of these viruses, as this review points out. Several countries have adopted immunization programs that recommend vaccination against HPV for girls and adolescents between 9 and 14 years of age and, in some of them, also for boys. The programs also contemplate the immunization of adults, particularly in the case of individuals with different immunodeficiencies. Sources of data: The available vaccines are recommended for the prevention of tumors of the uter-ine cervix, vulva, vagina, penis, and anal canal. Moreover, two of the vaccines prevent the occur-rence of genital warts, having been recently indicated for the prevention of oropharyngeal cancer. Data synthesis: Based on the evidence that antibody responses in girls were non-inferior after two doses when compared to three doses, several countries have decided to reduce the vaccination schedule for girls and boys up to 14 years of age from three to two doses, with an interval of six months between them. Recently, knowledge has been accumulating about the immunogenicity, duration of protection, and efficacy of a single-dose HPV vaccine regimen in girls and young women. Conclusion: Single-dose HPV vaccination could substantially reduce the incidence of pre-cancer and cervical cancer attributable to HPV, with reduced costs for vaccine delivery and simplified implementation, allowing more countries to introduce HPV vaccination or increase the adher-ence of the target population.(c) 2023 Published by Elsevier Editora Ltda. on behalf of Sociedade Brasileira de Pediatria. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).
- Human Papillomavirus Positivity at 3 Anatomical Sites Among Transgender Women in Central Brazil(2023) OLIVEIRA, Brunna Rodrigues de; SILVA, Bruno Vinicius Diniz E.; SANTOS, Kamila Cardoso dos; CAETANO, Karlla Antonieta Amorim; MOTA, Giana; SADDI, Vera Aparecida; RABELO-SANTOS, Silvia Helena; VILLA, Luisa Lina; VADDIPARTI, Krishna; COOK, Robert L.; TELES, Sheila Araujo; CARNEIRO, Megmar Aparecida dos SantosBackgroundTransgender women (TGW) are susceptible to the acquisition of sexually transmitted infections (STIs), including human papillomavirus (HPV). Nonetheless, the exact data for this population are scarce. We estimated HPV positivity at the anal, genital, and oral sites among TGW and also identified the related characteristics and behaviors that could be risk factors for HPV infection in a sample of TGW in Brazil. Furthermore, we characterized the site-specific HPV genotypes among those who were positive for HPV at these 3 sites.MethodsA cross-sectional study was conducted on TGW in Goiania City (Central-Midwest region), Brazil, between April 2018 and August 2019. Respondent-driven sampling was applied for recruitment. Next, self-collected anal, genital, and oral samples were examined for HPV DNA using polymerase chain reaction (SPF-10 primer). Human papillomavirus genotypes were identified in 12 TGW.ResultsIn the TGW included in the study, the anal, genital, and oral HPV positivity values were 77.2% (95% confidence interval [CI], 67.3%-84.6%), 33.5% (95% CI, 26.1%-48.9%), and 10.9% (95% CI, 5.8%-17.0%), respectively. In addition, the majority of 12 participants who tested for HPV had multiple genotypes. HPV-52 was the most prevalent genotype identified at the anal (66.6%) and genital (40.0%) sites, whereas HPV-62 and HPV-66 were the most common at the oral site (25.0%).ConclusionsA high HPV positivity was observed among TGW. Therefore, additional epidemiological studies on HPV genotypes should generate health intervention information, including the prevention, diagnosis, and treatment of sexually transmitted infections.
- Perianal fistulizing Crohn's disease is associated with a higher prevalence of HPV in the anorectal fistula tract. A comparative study(2023) BOARINI, Lucas Rodrigues; SOBRADO, Carlos Walter; MOTA, Giana Rabello; VILLA, Luisa Lina; ALBUQUERQUE, Idblan Carvalho de; QUEIROZ, Natalia Sousa Freitas; FACANALI, Carolina Bortolozzo Graciolli; NADAL, Sidney Roberto; CECCONELLO, IvanBackground & Aims: Perianal fistulizing Crohn's disease is the main risk factor for anal cancer in patients with inflammatory bowel disease. Whether this occurs due to a higher frequency of human papillomavirus remains unclear. The authors aimed to evaluate the prevalence of HPV and high-risk HPV in patients with perianal Crohn's disease, compared with a control group. Methods: The authors conducted a two-center cross-sectional study in which perianal fistulizing Crohn's disease patients were matched for age and sex with patients with anorectal fistula without Crohn's disease. Biopsy specimens were obtained from fistulous tracts during examination under anesthesia for both groups. The samples were sent for HPV detection and genotyping using the INNO-LiPA test. Results: A total of 108 subjects (54 in each group) were recruited. The perianal fistulizing Crohn's disease group showed a statistically higher frequency of HPV in the fistulous tract than the control group (33.3% vs. 16.7%; p = 0.046). Separate analyses on high-risk types demonstrated that there was a numerically higher frequency of HPV in the perianal fistulizing Crohn's disease group. In multiple logistic regression, patients with perianal fistulizing Crohn's disease were found to have a chance of HPV 3.29 times higher than patients without Crohn's disease (OR = 3.29; 95% CI 1.20-9.01), regardless of other variables. The types most frequently identified in the perianal fistulizing Crohn's disease group were HPV 11 (12.96%) and HPV 16 (9.26%). Conclusion: Perianal fistulizing Crohn's disease is associated with a higher prevalence of HPV than in patients with anorectal fistula without Crohn's disease.
- Human Papillomavirus Intermittence and Risk Factors Associated With First Detections and Redetections in the Ludwig-McGill Cohort Study of Adult Women(2023) MALAGON, Talia; TROTTIER, Helen; EL-ZEIN, Mariam; VILLA, Luisa L.; FRANCO, Eduardo L.; PAULO, SaoBackground We assessed the incidence and risk factors for first detection and redetection with the same human papillomavirus (HPV) genotype, and prevalence of cytological lesions during HPV redetections. Methods The Ludwig-McGill cohort study followed women aged 18-60 years from Sao Paulo, Brazil in 1993-1997 for up to 10 years. Women provided cervical samples for cytology testing and HPV DNA testing at each visit. A redetection was defined as a recurring genotype-specific HPV positive result after 1 or more intervening negative visits. Predictors of genotype-specific redetection were assessed using adjusted hazard ratios (aHR) with Cox regression modeling. Results In total, 2184 women contributed 2368 incident HPV genotype-specific first detections and 308 genotype-specific redetections over a median follow-up of 6.5 years. The cumulative incidence of redetection with the same genotype was 6.6% at 1 year and 14.8% at 5 years after the loss of positivity of the first detection. Neither age (aHR 0.90; 95% confidence interval [CI], .54-1.47 for >= 45 years vs < 25 years) nor new sexual partner acquisition (aHR 0.98; 95% CI, .70-1.35) were statistically associated with genotype-specific redetection. High-grade squamous intraepithelial lesion prevalence was similar during first HPV detections (2.9%) and redetection (3.2%). Conclusions Our findings suggest many HPV redetections were likely reactivations of latent recurring infections. Incidence of redetection with the same human papillomavirus genotype was found to be substantially higher than incidence of first detection. Redetections were not associated with new sexual partners. This suggests many human papillomavirus detections could be recurring latent infections.
- CD40/CD40L expression and its prognostic value in cervical cancer(2023) GRAZIA, G. A.; BASTOS, D. R.; VILLA, L. L.CD40, a member of the tumor necrosis factor receptor (TNFR) family, is known to be involved in immune system regulation, acting as a costimulatory molecule, and in antitumor responses against cancer cells. It is a protein that is expressed in different types of cells, including immune cells and cancer cells (e.g., cervical cancer, breast cancer, melanoma). In this study, we investigated CD40/CD40L transcriptional and protein levels in cervical cancer cell lines and tumors. Higher CD40 expression was observed in cervical cancer cell lines derived from squamous cell carcinomas than from adenocarcinomas. Search of CD40/CD40L expression in cervical cancer tissues in public data sets revealed that about 83% of squamous cell carcinomas express CD40 compared to other cervical tumor subtypes. Moreover, expression of CD40 and CD40L in squamous cervical carcinomas is associated with better overall survival. Therefore, these proteins could be explored as prognostic markers in cervical cancers.
- Understanding the public health value and defining preferred product characteristics for therapeutic human papillomavirus (HPV) vaccines: World Health Organization consultations, October 2021-March 2022(2022) PRUDDEN, Holly J.; ACHILLES, Sharon L.; SCHOCKEN, Celina; BROUTET, Nathalie; CANFELL, Karen; AKABA, Hiroki; BASU, Partha; BHATLA, Neerja; CHIRENJE, Z. Mike; DELANY-MORETLWE, Sinead; DENNY, Lynette; GAMAGE, Deepa G.; HERRERO, Rolando; HUTUBESSY, Raymond; VILLA, Luisa Lina; MURILLO, Raul; SCHILLER, John T.; STANLEY, Margaret; TEMMERMAN, Marleen; ZHAO, Fanghui; OGILVIE, Gina; KASLOW, David C.; DULL, Peter; GOTTLIEB, SamiThe World Health Organization (WHO) global strategy to eliminate cervical cancer (CxCa) could result in >62 million lives saved by 2120 if strategy targets are reached and maintained: 90% of adolescent girls receiving prophylactic human papillomavirus (HPV) vaccine, 70% of women receiving twice-lifetime cer-vical cancer screening, and 90% of cervical pre-cancer lesions and invasive CxCa treated. However, the cost and complexity of CxCa screening and treatment approaches has hampered scale-up, particularly in low-and middle-income countries (LMICs), and new approaches are needed. Therapeutic HPV vaccines (TxV), which could clear persistent high-risk HPV infection and/or cause regression of pre-cancerous lesions, are in early clinical development and might offer one such approach. During October 2021 to March 2022, WHO, in collaboration with the Bill and Melinda Gates Foundation, convened a series of glo-bal expert consultations to lay the groundwork for understanding the potential value of TxV in the con-text of current CxCa prevention efforts and for defining WHO preferred product characteristics (PPCs) for TxV. WHO PPCs describe preferences for vaccine attributes that would help optimize vaccine value and use in meeting the global public health need. This paper reports on the main discussion points and find-ings from the expert consultations. Experts identified several ways in which TxV might address chal-lenges in current CxCa prevention programmes, but emphasized that the potential value of TxV will depend on their degree of efficacy and how quickly they can be developed and implemented relative to ongoing scale-up of existing interventions. Consultation participants also discussed potential use -cases for TxV, important PPC considerations (e.g., vaccine indications, target populations, and delivery strategies), and critical modelling needs for predicting TxV impact and cost-effectiveness.(c) 2022 Published by Elsevier Ltd.
- Association Between Human Leukocyte Antigen Polymorphism and Human Papillomavirus Infection in Brazilian Women(2023) ARAUJO-SOUZA, Patricia Savio de; EL-ZEIN, Mariam; BOLPETTI, Aline do N.; MACIAG, Paulo Cesar; RABACHINI, Tatiana; FRANCO, Eduardo L.; VILLA, Luisa L.A prospective study of human papillomavirus infections and risk of cervical neoplasia in Brazilian women found that human leukocyte antigen polymorphisms may influence the natural history of these infections. BackgroundHuman papillomavirus (HPV) infection is a necessary cause for cervical cancer, but a majority of genital HPV infections clear spontaneously. Human leukocyte antigen (HLA) polymorphism influences immune response and genetic susceptibility, and its association with cervical cancer was extensively investigated, but few reports focused on HPV infection.MethodsWe performed molecular typing of HLA-A, HLA-B, HLA-DQB1, and HLA-DRB1 genes as well as of HPV in 1226 women enrolled in the Ludwig-McGill cohort study and investigated the influence on cumulative HPV positivity. HPV types were grouped according to Alphapapillomavirus subgenera that exhibit similar tissue tropism and biological behavior concerning cancer risk. The associations between HLA polymorphisms and HPV infections were estimated using unconditional logistic regression analysis adjusted for age and race.ResultsHLA-B*08 and HLA-DRB1*15:01 were negatively associated with HPV positivity, and similar effects were observed for HPV subgenus 2 only, which includes HPV16. HLA-DRB1*08:07 was associated with overall HPV infection and subgenus 2 positivity. The haplotypes HLA-B*08-DRB1*03:01-DQB1*02:01 and HLA-DRB1*08:07-DQB1*04:02 were negatively and positively associated with cumulative HPV positivity, respectively.ConclusionsOur data suggest that HLA class I and II polymorphism can influence HPV natural infection.
- Detection of serum biomarkers of HPV-16 driven oropharynx and oral cavity cancer in Brazil(2024) SICHERO, Laura; GONCALVES, Milena Giulia; BETTONI, Fabiana; COSER, Elisangela Monteiro; MOTA, Giana; NUNES, Rafaella A. L.; MERCANTE, Ana Maria da Cunha; NATALINO, Renato; UNO, Miyuki; ALVES, Maria Jose Ferreira; MATOS, Leandro Luongo; KOWALSKI, Luiz Paulo; KULCSAR, Marco Aurelio Vamondes; ALVARENGA, Gustavo Fernandes de; HOEFLER, Daniela; SCHROEDER, Lea; WATERBOER, Tim; TOMMASINO, Massimo; VILLA, Luisa LinaBackground: HPV-16 driven oropharynx/oral cavity squamous cell carcinomas prevalence varies globally. We evaluated the presence of HPV-16 ctDNA and HPV-16 E6 antibodies in samples obtained from participants treated at the Instituto do Cancer do Estado de Sao Paulo, ICESP, and from whom tumoral HPV DNA, HPV-16 E6*I mRNA, and p16(INK4a) status was also accessed. Methods: HPV was genotyped by PCR-hybridization. All HPV DNA positive and similar to 10 % HPV DNA negative cases underwent p16(INK4a) immunohistochemistry and E6*I RNA testing using a multiplex bead based protocol. HPV-16 ctDNA and anti-E6 antibodies were assessed by ddPCR (digital droplet PCR) and multiplex serology, respectively. Results: The prevalence of HPV-16 in oropharynx carcinoma (OPC) cases was low (8.7 %) when considering solely HPV-16 DNA detection, and even lower (5.2 %) when taken into consideration the concomitant detection of HPV-16 E6*I RNA and/or p16(INK4) (HPV-16 attributable fraction - AF). None of the oral cavity cancer (OCC) cases were detected with HPV-16 DNA. HPV-16 ctDNA was more commonly detected than HPV-16 E6 antibodies (29.8 % versus 10.6 %). Both serum biomarkers attained 100 % sensitivity of detecting HPV-16 AF OPC, however the specificity of the HPV-16 anti-E6 biomarker was higher compared to ctDNA (93.2 % versus 75.0 %). Finally, when both HPV-16 ctDNA and anti-E6 biomarkers were considered together, the sensitivity and specificity for HPV-16 OPC detection was 100 % and about 70 %, respectively, independently of analyzing HPV-16 DNA positive or HPV-16 AF tumors. Conclusions: Our findings corroborate that serum biomarkers are highly sensitive and specific biomarkers for detection of HPV-associated OPC.
- Control of Epstein-Barr Virus (EBV) in the Oral Cavity Is Associated With Persistence of Oral Human Papillomavirus (HPV)16/18 Among Men From the HPV Infection in Men Study(2023) DICKEY, Brittney L.; GIULIANO, Anna R.; SIRAK, Bradley; ABRAHAMSEN, Martha; LAZCANO-PONCE, Eduardo; VILLA, Luisa L.; COGHILL, Anna E.Detection of oral EBV shedding was significantly associated with the persistence of an oral HPV16/18 infection to at least 12 months. EBV coinfection therefore deserves further evaluation in its association with oral HPV persistence. Background Human papillomavirus (HPV)-related oropharyngeal cancer (OPC) incidence is increasing among men. Biomarkers that can identify oral HPV16/18 infections likely to persist, the obligate precursor for HPV-OPC, are needed. Methods We assessed the association between oral Epstein-Barr virus (EBV) and oral HPV16/18 persistence among 63 men in the HPV Infection in Men Study who tested positive for HPV16/18 at the baseline visit. Control of oral coinfections, including EBV, could serve as a biomarker of immune competence and the ability to control oral HPV. Results Detection of oral EBV was significantly associated with oral HPV16/18 >= 12-month persistence. Conclusions Detection of oral EBV deserves evaluation as a biomarker for oral HPV persistence and HPV-related OPC.