HPV 18 variants in women with cervical cancer in Northeast Brazil.

BACKGROUND: Human Papillomavirus (HPV) is the main etiological factor for the development of cervical cancer. HPV 18 is the second most frequent type, accounting for up to 65% of all cases. HPV intratypic variation may influence the potential for progression to invasive cancer. The aim of this study was to evaluate the prevalence of human papillomavirus 18 intratypic variants in cervical cancer samples from women in the state of Maranhão, Brazil. METHODS: The study included 118 women over 18 years of age with a diagnosis of cervical cancer. Tumor fragments were collected and subjected to DNA extraction and Polymerase Chain Reaction (PCR) for HPV detection using the PGMY09/11 and GP+5/6 primers. Positive samples were submitted to automated sequencing for viral genotyping. To determine the HPV 18 lineages, positive samples were submitted to PCR, using specific primers to amplify the LCR and E6 regions of HPV 18 virus. RESULTS: HPV was present in 88 women (73.3%). Of those, 48 (54%) were HPV 16, the most prevalent, followed by 12 (13.6%) HPV 18. Histologically, squamous cell carcinoma was predominant (79.1%). Among the HPV 18 variants identified, 10 (80%) belonged to lineage A, and sublineages A1, A2, A3, and A4. Two (29%) HPV 18 B variant was also detected, with the sublineages B1 and B2. In this study, the C variant was not found. There was no statistically significant association between the HPV 18 lineages found and sociodemographic and lifestyle variables (p > 0.05). CONCLUSIONS: A higher frequency of HPV 16 and 18 were found in women with cervical cancer in the state of Maranhão, Brazil, with a high prevalence of the lineage A among women with HPV 18.

HPV 18 variants in women with cervical cancer in Northeast Brazil

Abstract Background Human Papillomavirus (HPV) is the main etiological factor for the development of cervical cancer. HPV 18 is the second most frequent type, accounting for up to 65% of all cases. HPV intratypic variation may influence the potential for progression to invasive cancer. The aim of this study was to evaluate the prevalence of human papillomavirus 18 intratypic variants in cervical cancer samples from women in the state of Maranhão, Brazil. Methods The study included 118 women over 18 years of age with a diagnosis of cervical cancer. Tumor fragments were collected and subjected to DNA extraction and Polymerase Chain Reaction (PCR) for HPV detection using the PGMY09/11 and GP+5/6 primers. Positive samples were submitted to automated sequencing for viral genotyping. To determine the HPV 18 lineages, positive samples were submitted to PCR, using specific primers to amplify the LCR and E6 regions of HPV 18 virus. Results HPV was present in 88 women (73.3%). Of those, 48 (54%) were HPV 16, the most prevalent, followed by 12 (13.6%) HPV 18. Histologically, squamous cell carcinoma was predominant (79.1%). Among the HPV 18 variants identified, 10 (80%) belonged to lineage A, and sublineages A1, A2, A3, and A4. Two (29%) HPV 18 B variant was also detected, with the sublineages B1 and B2. In this study, the C variant was not found. There was no statistically significant association between the HPV 18 lineages found and sociodemographic and lifestyle variables (p > 0.05). Conclusions A higher frequency of HPV 16 and 18 were found in women with cervical cancer in the state of Maranhão, Brazil, with a high prevalence of the lineage A among women with HPV 18.

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

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.

The papillomavirus E5 gene does not affect EGFR transcription and overall survival in cervical cancer.

INTRODUCTION: The human papillomavirus (HPV) E5 gene encodes a small and highly hydrophobic oncoprotein that affects immune evasion, cell proliferation, loss of apoptotic capacity and angiogenesis in tumors. E5 shows an affinity for biological membranes and was associated with an increase of epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) signaling through the accumulation of EGFR in cellular membranes. Due to the frequent integration of the HPV genome into the host cell genome, E5 is frequently not transcribed in cervical tumors. AIM: In this study we looked forward to verifying whether the potential expression of E5 protein in human papillomavirus 16 positive (HPV16+ ) and human papillomavirus 18 positive (HPV18+ ) cervical tumors was associated with levels of EGFR and vascular endothelial growth factor A (VEGFA) transcription and with patients overall survival. RESULTS: Association between the presence of E5 transcripts and viral genome disruption was observed for HPV16+ and HPV18+ tumors. Association was not observed between tumors potentially capable of translating E5 and EGFR or VEGFA transcriptional levels. Similarly, the capability of translating E5 and overall survival in patients with HPV16+ squamous cell carcinoma tumors stage ≥ IB2 were not associated. CONCLUSION: The likely presence of E5 transcripts was neither associated to a higher activity of the EGFR-VEGFA pathway nor to the overall survival of patients with HPV16+ squamous cell carcinoma in stages ≥ IB2.

Human papillomavirus type 18 E5 oncoprotein cooperates with E6 and E7 in promoting cell viability and invasion and in modulating the cellular redox state

BACKGROUND High-risk human papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer. Among them, types 16 and 18 are the most prevalent worldwide. The HPV genome encodes three oncoproteins (E5, E6, and E7) that possess a high transformation potential in culture cells when transduced simultaneously. In the present study, we analysed how these oncoproteins cooperate to boost key cancer cell features such as uncontrolled cell proliferation, invasion potential, and cellular redox state imbalance. Oxidative stress is known to contribute to the carcinogenic process, as reactive oxygen species (ROS) constitute a potentially harmful by-product of many cellular reactions, and an efficient clearance mechanism is therefore required. Cells infected with HR-HPVs can adapt to oxidative stress conditions by upregulating the formation of endogenous antioxidants such as catalase, glutathione (GSH), and peroxiredoxin (PRX). OBJECTIVES The primary aim of this work was to study how these oncoproteins cooperate to promote the development of certain cancer cell features such as uncontrolled cell proliferation, invasion potential, and oxidative stress that are known to aid in the carcinogenic process. METHODS To perform this study, we generated three different HaCaT cell lines using retroviral transduction that stably expressed combinations of HPV-18 oncogenes that included HaCaT E5-18, HaCaT E6/E7-18, and HaCaT E5/E6/E7-18. FINDINGS Our results revealed a statistically significant increment in cell viability as measured by MTT assay, cell proliferation, and invasion assays in the cell line containing the three viral oncogenes. Additionally, we observed that cells expressing HPV-18 E5/E6/E7 exhibited a decrease in catalase activity and a significant augmentation of GSH and PRX1 levels relative to those of E5, E6/E7, and HaCaT cells. MAIN CONCLUSIONS This study demonstrates for the first time that HPV-18 E5, E6, and E7 oncoproteins can cooperate to enhance malignant transformation.

E6/E7 and E6* From HPV16 and HPV18 Upregulate IL-6 Expression Independently of p53 in Keratinocytes.

Keratinocyte infection with high-risk human papillomavirus genotypes has been linked to cancer development. In cervix, the alpha HPV16 and HPV18 have been reported as the mayor causative agents of cervical cancer. Oncogenic progression and chronic inflammation are closely related processes, with IL-6 as one of the main pro-inflammatory cytokines involved. However, there are limited studies about the regulation of IL-6 by low and high risk HPVs and the HPV proteins implicated in this modulation. In this work, we report the overexpression of IL-6 in HPV infected cervical cancer derived cell lines (HeLa and SiHa) compared to non-tumorigenic keratinocytes (HaCaT), and in Cervical Intraepithelial Neoplasia grade 1 HPV16 and HPV18 positive cervical samples compared to HPV negative samples without lesions. Moreover, we generated HaCaT keratinocytes that express E5, E6, and E7 from high risk (16 or 18) or low risk (62 and 84) HPVs. E5 proteins do not modify IL-6 expression, while E7 modestly increase it. Interestingly, E6 proteins in HaCaT cells upregulate IL-6 mRNA expression and protein secretion. Indeed, in HaCaT cells that express high risk HPV16E6 or HPV18E6 proteins, only the truncated E6* isoforms were expressed, showing the stronger IL-6 overexpression, while in HaCaT cells that express low risk HPV62 and HPV84 full length E6 proteins, IL-6 was also upregulated but not so drastically. Since HaCaT cells have a mutated p53 form that is not degraded by the introduction of E6 or E6/E7, it seems that E6/E7 regulate IL-6 by an additional mechanism independent of p53. In addition, basal keratinocytes showed a strong expression of IL-6R using immunohistochemistry, suggesting an autocrine mechanism over proliferative cells. Altogether, IL-6 cytokine expression in keratinocytes is upregulated by E6 and E7 proteins from HPVs 16, 18, 62, and 84, especially by high risk HPV16 and HPV18 E6*, which may contribute to promote a pro-inflammatory and highly proliferative microenvironment that can persist over time and lead to cervical tumorigenesis.

E6 Oncoproteins from High-Risk Human Papillomavirus Induce Mitochondrial Metabolism in a Head and Neck Squamous Cell Carcinoma Model.

Head and neck squamous cell carcinoma (HNSCC) cells that are positive for human papillomavirus (HPV+) favor mitochondrial metabolism rather than glucose metabolism. However, the involvement of mitochondrial metabolism in HNSCC HPV+ cells is still unknown. The aim of this work was to evaluate the role of E6 oncoproteins from HPV16 and HPV18 in the mitochondrial metabolism in an HNSCC model. We found that E6 from both viral types abates the phosphorylation of protein kinase B-serine 473 (pAkt), which is associated with a shift in mitochondrial metabolism. E6 oncoproteins increased the levels of protein subunits of mitochondrial complexes (I to IV), as well as the ATP synthase and the protein levels of the voltage dependent anion channel (VDAC). Although E6 proteins increased the basal and leak respiration, the ATP-linked respiration was not affected, which resulted in mitochondrial decoupling. This increase in leak respiration was associated to the induction of oxidative stress (OS) in cells expressing E6, as it was observed by the fall in the glutathione/glutathione disulfide (GSH/GSSG) rate and the increase in reactive oxygen species (ROS), carbonylated proteins, and DNA damage. Taken together, our results suggest that E6 oncoproteins from HPV16 and HPV18 are inducers of mitochondrial metabolism.

HPV-18 E6 Oncoprotein and Its Spliced Isoform E6*I Regulate the Wnt/ß-Catenin Cell Signaling Pathway through the TCF-4 Transcriptional Factor.

The Wnt/ß-catenin signaling pathway regulates cell proliferation and differentiation and its aberrant activation in cervical cancer has been described. Persistent infection with high risk human papillomavirus (HR-HPV) is the most important factor for the development of this neoplasia, since E6 and E7 viral oncoproteins alter cellular processes, promoting cervical cancer development. A role of HPV-16 E6 in Wnt/ß-catenin signaling has been proposed, although the participation of HPV-18 E6 has not been previously studied. The aim of this work was to investigate the participation of HPV-18 E6 and E6*I, in the regulation of the Wnt/ß-catenin signaling pathway. Here, we show that E6 proteins up-regulate TCF-4 transcriptional activity and promote overexpression of Wnt target genes. In addition, it was demonstrated that E6 and E6*I bind to the TCF-4 (T cell factor 4) and ß-catenin, impacting TCF-4 stabilization. We found that both E6 and E6*I proteins interact with the promoter of Sp5, in vitro and in vivo. Moreover, although differences in TCF-4 transcriptional activation were found among E6 intratype variants, no changes were observed in the levels of regulated genes. Furthermore, our data support that E6 proteins cooperate with ß-catenin to promote cell proliferation.

A high prevalence of human papillomavirus 16 and 18 co-infections in cervical biopsies from southern Brazil.

HPV types 16 and 18 were studied in paraffin-fixed cervical biopsy collected in southern Brazil. HPV 16, HPV 18 and co-infection HPV 16/18 were identified in 10/57 (17.5%), 4/57 (7%) and in 43/57 (75.4%) samples, respectively. Southern Brazil has one of the highest prevalence rates of HPV 16/18 reported.

HPV-18 E2 protein downregulates antisense noncoding mitochondrial RNA-2, delaying replicative senescence of human keratinocytes.

Human and mouse cells display a differential expression pattern of a family of mitochondrial noncoding RNAs (ncmtRNAs), according to proliferative status. Normal proliferating and cancer cells express a sense ncmtRNA (SncmtRNA), which seems to be required for cell proliferation, and two antisense transcripts referred to as ASncmtRNA-1 and -2. Remarkably however, the ASncmtRNAs are downregulated in human and mouse cancer cells, including HeLa and SiHa cells, transformed with HPV-18 and HPV-16, respectively. HPV E2 protein is considered a tumor suppressor in the context of high-risk HPV-induced transformation and therefore, to explore the mechanisms involved in the downregulation of ASncmtRNAs during tumorigenesis, we studied human foreskin keratinocytes (HFK) transduced with lentiviral-encoded HPV-18 E2. Transduced cells displayed a significantly extended replicative lifespan of up to 23 population doublings, compared to 8 in control cells, together with downregulation of the ASncmtRNAs. At 26 population doublings, cells transduced with E2 were arrested at G2/M, together with downregulation of E2 and SncmtRNA and upregulation of ASncmtRNA-2. Our results suggest a role for high-risk HPV E2 protein in cellular immortalization. Additionally, we propose a new cellular phenotype according to the expression of the SncmtRNA and the ASncmtRNAs.

A high prevalence of human papillomavirus 16 and 18 co-infections in cervical biopsies from southern Brazil

ABSTRACT HPV types 16 and 18 were studied in paraffin-fixed cervical biopsy collected in southern Brazil. HPV 16, HPV 18 and co-infection HPV 16/18 were identified in 10/57 (17.5%), 4/57 (7%) and in 43/57 (75.4%) samples, respectively. Southern Brazil has one of the highest prevalence rates of HPV 16/18 reported.

A high prevalence of human papillomavirus 16 and 18 co-infections in cervical biopsies from southern Brazil

ABSTRACT HPV types 16 and 18 were studied in paraffin-fixed cervical biopsy collected in southern Brazil. HPV 16, HPV 18 and co-infection HPV 16/18 were identified in 10/57 (17.5%), 4/57 (7%) and in 43/57 (75.4%) samples, respectively. Southern Brazil has one of the highest prevalence rates of HPV 16/18 reported.

A high prevalence of human papillomavirus 16 and 18 co-infections in cervical biopsies from southern Brazil

HPV types 16 and 18 were studied in paraffin-fixed cervical biopsy collected in southern Brazil. HPV 16, HPV 18 and co-infection HPV 16/18 were identified in 10/57 (17.5%), 4/57 (7%) and in 43/57 (75.4%) samples, respectively. Southern Brazil has one of the highest prevalence rates of HPV 16/18 reported.(AU)

Prevalência de câncer colorretal associado ao papilomavírus humano: uma revisão sistemática com metanálise / Colorectal cancer prevalence linked to human papillomavirus: a systematic review with meta-analysis

RESUMO: Introdução: O câncer colorretal é um dos tipos de tumor mais prevalentes na população mundial. A mortalidade causada por esses tumores malignos continua elevada e mantém-se praticamente no mesmo nível nas últimas décadas. Entre os fatores de risco já estabelecidos para o desenvolvimento do câncer estão as infecções por patógenos ou vírus. Entre os vírus, o papilomavírus humano (HPV) é o mais prevalente, tendo mais de 180 cepas, das quais 40 estão diretamente relacionadas com infecções anogenitais. Objetivo: Avaliar de forma sistemática, com metanálise, os principais estudos que associam o HPV ao câncer colorretal. Métodos: Como estratégia de busca foi adotada a lógica baseada em descritores específicos (idioma inglês), vinculados aos operadores booleanos (AND/OR). As buscas foram aplicadas nas bases de dados PubMed, ScienceDirect e Scientific Electronic Library Online (SciELO), no período de abril e maio de 2015. Resultados: Foram avaliadas 1.549 amostras, sendo 956 (61,7%) do sexo masculino. Foram diagnosticados 630/1.358 casos de câncer colorretal por HPV (51,9%). Destes, 408/767 (51,9%) eram do sexo masculino e 404/598 (67,5%) foram associados aos HPVs 16 e 18, com prevalência tumoral na região do colo (253/411; 61,3%). Do total de 598 amostras para estimativa das prevalências de HPV-16 e HPV-18, a quantidade de casos com valores muito semelhantes foi de 204 (31,7%) e 200 (35,8%), respectivamente. Foram verificados valores relativamente expressivos na região do colo, 253 (61,3%), e na região retal, 158 (38,7%). Conclusão: Após a realização do presente estudo, a associação entre HPV e câncer colorretal ficou evidente, não havendo distinção entre gêneros, com valores muito semelhantes entre o HPV-16 e o HPV-18.

ABSTRACT: Introduction: Colorectal cancer is one of the most prevalent types of tumors worldwide. Deaths caused by these malignant tumors remain high and have stayed practically at the same level for the last few decades. Among the established risk factors for the development of cancer are infections due to pathogens or viruses. Among the viruses, the human papillomavirus (HPV) is the most prevalent, with over 180 strains, 40 of which are directly related to anogenital infections. Objective: Systematically assess the main studies which link HPV to colorectal cancer with meta-analysis. Methods: The search strategy adopted was the logic based on specific descriptors (English language), in combination with the Boolean operators (AND/OR). The search was conducted in the following databases: PubMed, ScienceDirect, and Scientific Electronic Library Online (SciELO), between April and May 2015. Results: 1,549 samples were assessed, with 956 (61.7%) being males. Six hundred thirty out of 1,358 cases of colorectal cancer due to HPV were diagnosed (51.9%). From these, 408 of 767 (51.9%) were male and 404 of 598 (67.5%) were linked to HPV 16 and 18, with tumor prevalence in the area of the cervix (253 of 411; 61.3%). From the total of 598 samples for the prevalence estimate of HPV 16 and 18, the number of cases with similar numbers was 204 (31.7%) and 200 (35.8%), respectively. Relatively significant numbers were found in the area of the cervix, 253 (61.3%), and the area of the rectum, 158 (38.7%). Conclusion: After conducting the present study, the link between HPV and colorectal cancer was made evident, without a distinction between the sexes, with similar values between HPV 16 and HPV 18.

Avances en el desarrollo de nuevas vacunas profilácticas y terapéuticas contra el Virus del Papiloma Humano / Advances in the development of new prophylactic and therapeutic vaccines against Human Papillomavirus

El uso de vacunas profilácticas contra el Virus del Papiloma Humano (VPH) de alto riesgo ha adquirido gran importancia debido al alto potencial oncogénico, de estos virus, especialmente por su asociación con el cáncer de cuello uterino, uno de los canceres más comunes y de mayor mortalidad en mujeres a nivel mundial. El objetivo de este artículo es describir las vacunas profilácticas y terapéuticas disponibles actualmente contra el VPH, analizando las características, ventajas, desventajas y estudios científicos sobre su uso y seguridad en la población. Se llevó a cabo una revisión de literatura de los últimos avances en el desarrollo de vacunas profilácticas y terapéuticas contra el VPH. La vacunación profiláctica es efectiva y esencial para la prevención del cáncer de cuello uterino causadas por VPH-16 y -18, pero no genera protección cruzada contra otros VPH de alto riesgo, esto ha encaminado a la creación de nuevas vacunas nanovalentes que protegen contra un número mas amplio de VPHs de alto riesgo. Por otra parte, las vacunas terapéuticas han demostrado en sus fases de estudio iniciales ser promisorias en la regresión de lesiones premalignas o malignas in situ.

Prophylactic vaccines against high risk HPV has become important because of the high oncogenic potential of the virus and its association with cervical cancer development, one of the most common and fatal cancers among women worldwide. The objective of this article is describe the state of the art of the current prophylactic and therapeutic HPV vaccines, analyzing their characteristics, advantages, disadvantages and scientific reports on its use and safety in the population. A systematic revision of the latest advances in the development of prophylactic and therapeutic vaccines against HPV was performed. Prophylactic vaccination is effective and essential for the prevention of uterine cervical cancer; new therapeutic vaccines have been shown at the initial phases to be promising contributing in the regression of premalignant or malignant in situ lesions.

HPV16/18 genotyping for the triage of HPV positive women in primary cervical cancer screening in Chile.

BACKGROUND: We previously conducted a population-based screening trial of high-risk human papillomavirus (hrHPV) testing and conventional cytology, demonstrating higher sensitivity (92.7 % vs 22.1 % for CIN2+) but lower positive predictive value (10.5 % vs 23.9 %) of hrHPV testing. Here we report the performance of HPV16/18 genotyping to triage the hrHPV positive participants. METHODS: Women aged 25 years and older received hrHPV (Hybrid Capture 2) and Papanicolaou testing; positives by either test underwent colposcopy and directed biopsy, as did a sample of double-negatives. hrHPV positive women were reflex-tested with HPV16/18 genotyping (Digene HPV Genotyping PS Test). RESULTS: Among the 8,265 participants, 10.7 % were hrHPV positive, 1.7 % had ASCUS+ cytology, 1.2 % had CIN2+; 776 (88 %) hrHPV positive women had complete results, of whom 38.8 % were positive for HPV16 (24.0 %), HPV18 (9.7 %) or both (5.1 %). CIN2+ prevalence in HPV16/18 positive women (16.3 %, 95 % CI 12.3-20.9) was twice that of HPV16/18 negative women (8.0 %, 95 % CI 5.7-10.8). HPV16/18 genotyping identified 40.5 % of CIN2, 66.7 % of CIN3 and 75.0 % of cancers. Compared to hrHPV screening alone, HPV16/18 triage significantly reduced the referral rate (10.7 % vs 3.7 %) and the number of colposcopies required to detect one CIN2+ (9 vs 6). When HPV16/18 negative women with baseline ASCUS+ cytology were also colposcopied, an additional 14 % of CIN2+ was identified; referral increased slightly to 4.2 %. CONCLUSIONS: HPV16/18 triage effectively stratified hrHPV positive women by their risk of high-grade lesions. HPV16/18 positive women must be referred immediately; referral could be deferred in HPV16/18 negative women given the slower progression of non-HPV16/18 lesions, however, they will require active follow-up.

Prevalence and risk factors for HPV infection in normal oral mucosa of chilean dentistry students / Prevalencia y factores de riesgo de infección por virus papiloma humano en mucosa oral normal de estudiantes de odontología chilenos

Abstract: aim: to determine the prevalence and risk factors for HPV infection in normal oral mucosa of Chilean dentistry students. Materials and methods: A cross-sectional study was performed. The study group was comprised of 103 individuals between 18 and 33 years old. A self-administered survey of cancer family history, sexual habits, smoking and alcohol drinking was applied. Oral mucosal samples were taken using a sterile swab. Subsequently, all samples were analyzed by polymerase chain reaction technique (PCR). Results: Results were negative for HPV detection in all analyses. Of the study population, 58 percent had a family history of cancer, 40.9 percent had had more than 3 sexual partners, 76.3 percent had sexual intercourse before the age of 19, 66.3 percent had engaged in oral sex, 69.9 percent drank alcohol and 20.6 percent were smokers. Conclusions: The group studied is exposed to various risk factors for HPV infection, so it is necessary to educate about the relationship between them and the spread of the virus. Despite the presence of risk factors, the detected prevalence of HPV was 0 percent.

Resumen: se realizó un estudio de corte transversal. El grupo de estudio fue constituido por 103 individuos entre 18 y 33 años. Se aplicó una encuesta autoadministrada sobre antecedentes familiares de cáncer, hábitos sexuales y consumo de tabaco y alcohol. Se tomaron muestras de la mucosa oral utilizando un hisopo estéril. Posteriormente, todas las muestras fueron analizadas mediante técnica de reacción en cadena de la polimerasa (PCR). Resultados: Los resultados fueron negativos para la detección de VPH en todos los análisis. De la población estudiada el 58 por ciento presentó antecedentes familiares de cáncer, el 40,9 por ciento ha tenido más de 3 parejas sexuales, el 76,3 por ciento se inició sexualmente antes de los 19 años, el 66,3 por ciento ha practicado sexo oral, un 69,9 por ciento es bebedor de alcohol y el 20,6 por ciento es fumador. Conclusiones: El grupo analizado está expuesto a diversos factores de riesgo de infección VPH, por lo que es necesario educar acerca de la relación entre estos y el contagio con el virus. A pesar de la presencia de factores de riesgo en los encuestados, la prevalencia detectada de VPH fue de 0 por ciento.

Human papilloma virus and oral cancer: narrative review of the literature / Virus papiloma humano y cáncer oral: revisión narrativa de la literatura

The Human Papilloma Virus (HPV) infection is now more common sexually transmitted diseases, with an incidence of 5.5 million worldwide, with 85 percent of the carrier of this virus adult population. Their oncogenic potential and increased oral lesions associated with oral HPV infection have led us to make a narrative of the literature on the role of HPV in oral cancer, especially types 16 and 18. Here we refer to the possible routes of infection, oncogenic mechanisms, both benign and potentially malignant oral lesions associated with the infection, different methods used for detection, prediction and prevention of infection. We stress the importance of the role of the dentist to identify individuals considered high risk and ease of performing detection in the oral cavity, through a quick and easy method as exfoliative cytology.

El Virus Papiloma Humano (VPH) en la actualidad constituye la infección por transmisión sexual más frecuente, presentando una incidencia de 5,5 millones en el mundo, siendo un 85 por ciento de la población adulta portadora de este virus. Su potencial oncogénico y el aumento de lesiones orales asociadas a infección oral por VPH nos han llevado a realizar una narración de la literatura referente al rol del VPH en el cáncer oral, especialmente de los subtipos 16 y 18. Nos referiremos a sus posibles vías de contagio, mecanismos oncogénicos, lesiones orales tanto benignas como potencialmente malignas asociadas a su infección, diferentes métodos utilizados para su detección, pronóstico y prevención de contagio. Destacamos la importancia del rol del odontólogo para identificar individuos considerados de alto riesgo y la facilidad de realizar su detección en la cavidad oral, a través de un método rápido y sencillo como es la citología exfoliativa.

Clinicopathological aspects and prevalence of human papillomavirus in anal cancer / Aspectos clínico-patológicos e prevalência do papilomavírus humano (HPV) em carcinomas anais

Anal cancer is relatively rare; however, its incidence has increased in recent years. Several risk factors are associated with the development of anal cancer, including age older than 50 years, low-fiber diet, chronic anal fistulas, smoking, multiple partners, anal intercourse practice, Human Immunodeficiency Virus infection and immunosuppression. However, the presence of human papillomavirus represents the main risk factor for the development of anal cancer. The aim of this study was to evaluate the clinicopathological aspects of a series of patients with anal carcinomas diagnosed in Hospital Araújo Jorge, Goiânia-Goiás, as well as the prevalence of human papillomavirus genome in these tumors. Clinical, pathological and socio-demographic data were collected from the respective medical files and paraffin blocks containing anal carcinomas specimens were used for DNA extraction and detection of human papillomavirus, by means of polymerase chain reaction, using short PCR fragment primers. Forty-three cases were selected and had the data analyzed, while 38 cases were tested for human papillomavirus genome detection. Among the evaluated patients, 62.8% were women; 53.4% of tumors were squamous cell carcinoma and 46.5% of the patients were aged between 60 and 75 years. Risk factors, such as smoking (39.5%) and alcoholism (20.9%) were recorded in the studied group. Lymph node metastases were detected in 30.2% of cases and 7.0% had distant metastasis. The detection of human papillomavirus DNA was positive in 76% of cases assessed and this was significantly associated with squamous cell carcinomas. Aggressive behavior and advanced stage of anal cancer described in this study highlight the need for preventive measures that contemplate these tumors, including vaccination against human papillomavirus. (AU)

O câncer anal é relativamente raro, entretanto, sua incidência aumentou nos últimos anos. Vários fatores de risco são associados ao desenvolvimento do câncer anal, incluindo idade maior que 50 anos, dieta pobre em fibras, fístulas anais crônicas, tabagismo, múltiplos parceiros, prática de intercurso anal, infecção pelo HIV e imunossupressão. Entretanto, a presença do Papilomavírus Humano (HPV) representa o principal fator de risco para o desenvolvimento do câncer anal. O objetivo deste estudo consistiu em avaliar os aspectos clínico-patológicos de uma série de pacientes com carcinomas anais diagnosticados no Hospital Araújo Jorge, Goiânia/GO, bem como a prevalência do genoma do HPV nesses tumores. Dados clínico-patológicos e sóciodemográficos foram colhidos a partir dos respectivos prontuários e blocos de parafina contendo espécimes de carcinomas anais foram usados para extração de DNA e detecção de HPV, por meio da reação em cadeia da polimerase, usando oligonucleotídeos iniciadores SPF. Quarenta e três casos foram selecionados e tiveram os dados clinico-patológicos analisados, enquanto 38 casos foram testados para a detecção do genoma do HPV. Dentre os pacientes avaliados, 62,8% eram mulheres; 53,4% dos tumores eram carcinomas de células escamosas e 46,5% dos pacientes estavam na faixa etária entre os 60 e 75 anos. Fatores de risco, como tabagismo (39,5%) e etilismo (20,9%) foram registrados no grupo estudado. Metástases linfonodais foram detectadas em 30,2% dos casos e 7,0% apresentaram metástase à distância. A detecção de HPV foi positiva em 76,0% dos casos analisados e este significativamente associado aos carcinomas de células escamosas. O comportamento agressivo e o estágio avançado dos carcinomas anais descritos no presente estudo destacam a necessidade de medidas de prevenção que contemplem esses tumores, incluindo a vacinação contra o HPV. (AU)

Regulation of p14ARF expression by HPV-18 E6 variants.

A common causative agent for uterine cervical cancer is the human papillomavirus type 18 (HPV-18) which has three phylogenic variants: Asian-Amerindian, European, and African. Each variant shows significant molecular differences in the E6 gene. E6 oncoprotein is a negative regulator of tumor suppressor protein p53, hence, this oncoprotein indirectly regulates the expression of tumor-suppressor p14(ARF) . p14(ARF) and p16(INK4A) genes are overexpressed in--and have been proposed as markers for--HPV-related cervical cancer. In order to dissect the role of E6 on the regulation of p14(ARF) expression, separating it from that of other intervening factors, transfection of E6 variants to MCF-7 cells was performed, assessing cDNA transcript levels by RT-PCR, whereas p14(ARF) and p53 expression were evaluated by immunocytochemistry and Western blot. E6 transfected cells differentially expressed transcripts of two molecular forms: E6 and E6*. The ratio of these two forms varied with the transfected E6 variant. With the Asian-Amerindian variant, the ratio was E6 > E6*, whereas with the European and the African the ratio was E6* > E6. As expected with the E6* construct, E6* transcripts were solely observed. In addition, when E6 > E6* and p53 expression was low, p14(ARF) was high and when E6* > E6 and p53 expression was high, p14(ARF) was low. In conclusion, each E6 variant distinctively affects p53 levels and consequently p14(ARF) expression, finding that could be related with the differences in oncogenic effect of infection with the diverse high-risk HPV variants.