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Abstract: Routine use of human papillomavirus (HPV) vaccines is recommended in adolescents under 15 years of age worldwide. Still, effective programs remain suboptimal for several factors, making the WHO strategy to eradicate cervical cancer public health with an uncertain future. Objective: To review the literature on the effectiveness, long-term protection, and safety of HPV vaccination programs and vaccination as adjuvant management. This review aims to describe the current state of vaccination programs and demonstrate the long-term protection and safety of vaccines implemented worldwide targeting adolescent girls, with the most recent published evidence of the three prophylactic HPV vaccines - bivalent (bHPV), quadrivalent (qHPV), and nonavalent (nHPV)-. We mainly focus on publications evaluating efficacy, dosing schemes, and HPV vaccination, as well as studies contributing to the mounting evidence for the real-life effectiveness of prophylactic HPV vaccines from several countries. Findings: Human Papillomavirus vaccination programs have made remarkable strides in preventing HPV-related diseases; countries with robust vaccination efforts have witnessed substantial reductions in HPV-related diseases with a decline in high-grade cervical abnormalities and genital warts (54%-83%). However, global coverage remains uneven, with disparities between high-income (HICs) and low-income countries (LMICs). The long-term efficacy of the available human papillomavirus (HPV) goes up to 9.4 years and continues to be immunogenic and well tolerated with an excellent safety profile. Conclusions and relevance: As these are crucial topics in HPV vaccination, it is essential to establish systems for continued monitoring of vaccine immunogenicity, efficacy, and safety over time.

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Sus scrofa papillomatosis (SsP) is a tumour caused by Sus scrofa papillomaviruses (SsPVs). To investigate the presence of SsPVs in China, 354 domestic pig skin samples collected from Guangxi Province were examined for SsPV DNA by PCR. Three SsPV1s (GX12, GX14, and GX18) were identified with a prevalence of 0.847% (3/354). Sequence analysis showed that L1 of SsPV1/GX12 and SsPV1/GX14 had 99.7% and 99.6% nucleotide identify with the reference SsPV1a, respectively. Phylogenetic and evolutionary analyses showed that SsPV1/GX12 and SsPV1/14 clustered into SsPV1a and that SsPV1/GX18 clustered into SsPV1b. Compared with other SsPV L1 and L2 proteins, we found that the SsPV1/GX18 and SsPV1b strains shared the same unique substitutions, and SsPV1/GX12, SsPV1/GX14, and SsPV1a shared almost identical amino acid sequences. This study reports the first detection of SsPV DNA in China based on whole genome information and provides a scientific basis for the development of SsPV pathogenic biology, epidemiology, and prevention, as well as control technology research.

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Thirty-one bovine cutaneous warts were submitted to macroscopic and histological analyses and to molecular analyses to partial amplification and sequencing of the L1 gene of bovine papillomavirus (BPV). Viral types detected were BPV1 (52%), BPV2 (29%), BPV6 (16%) and BPV10 (3%). BPV2 had lower frequency in papilloma in comparison to that in fibropapilloma (p = 0.002).

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Introducción:la citología cérvicovaginal es una prueba de tamizaje para detectar las neoplasias intracervicales (NIC), que ha disminuido la incidencia y la mortalidad por cáncer de cuello uterino (CCU). El diagnóstico del NIC es más frecuente entre los 20 y 30 años y el de CCU tiene una mayor frecuencia entre los 30 y 40 años. Desde 1983 a 1991 la tasa de mortalidad por CCU en Colombia fue de 6,5/100.000 habitantes y el 50% de estos casos murieron por diagnóstico tardío. Aunque se divulga que la infección por el papilomavirus es la causa necesaria, no es suficiente para el desarrollo del CCU. Objetivo:determinar una relación entre VPH y el desarrollo de NIC y CCU.Materiales y métodos:se revisaron 11.992 citologías vaginales en el período de un año, y a las VPH positivas por patología se les realizó biopsia de cérvix. Resultados:hay mayor probabilidad de adquirir VPH entre los 30 y 39 años, que se reduce en menores de 19 y mayores de 50 años. Con la sola presencia del virus la probabilidad de desarrollar NIC-I es de 5.8%, la de desarrollar NICII-III es de 0.29% y la de desarrollar CCU es de 0.08%. Conclusiones: se encontraron9 casos de CCU en 735 citologías con VPH diagnosticadas por patología, que corresponde al 1.2%; y una probabilidad del 0.08% para el desarrollo del cáncer, teniendo en cuenta solo la presencia del VPH. Este resultado sugiere que se necesitan otros factores para el desarrollo del cáncer.

Introduction: cervical Pap smear is a test to detect potentially malignant cervical neoplasia (CIN), which has decreased the incidence and mortality from cervical (cervical cancer) cancer. NIC diagnosis is most common between 20 and 30 years and the cervical cancer has a higher frequency between 30 and 40 years. From 1983 to 1991, the mortality rate for cervical cancer in Colombia was 6.5 / 100,000 and 50% of these cases died late diagnosis. Although it is accepted that infection with human papillomavirus (HPV) is the necessary cause, itis not enough for the development of cervical cancer.Objective:to determine a relationship between HPV and cervical cancer development and NIC.Materials and Methods:11,992 Pap smears were reviewed in the period of one year and a positive HPV pathologyunderwent cervical biopsy.Results:no more likely to get HPV between 30 and 39, which is reduced by less than 19 and older than 50 years. The mere presence of the virus the probability of developing CIN-I is 5.8%, to develop NICII-III is 0.29% and that of developing cervical cancer is 0.08%.Conclusions:9 cases of cervical cancer were found in 735 HPV diagnosed by cytological pathology, corresponding to 1.2%; and a probability of 0.08% to cancer development, taking into account only the presence of HPV. This result suggests that other factors for cancer development are needed.

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A placa aural é uma dermatopatia associada à quatro Equus caballus papillomavirus (EcPVs). Até o momento, o DNA de EcPVs não foi identificado em amostras de placa aural fixadas em formalina e embebidas em parafina (FFPE). O objetivo deste estudo foi otimizar um método para a detecção dos quatro tipos de EcPVs em 21 amostras FFPE usando a PCR. O DNA dos EcPVs foram detectados em 11 amostras (52.4%). O DNA do EcPV4 foi detectado em 38.1% (8/21) e do EcPV3 em 4.8% (1/21) das amostras. Coinfecção foi identificada em duas amostras (9.5%); EcPV4 e 5 foram detectados simultaneamente em uma amostra, enquanto o DNA dos EcPV4 e 6 foi detectado em outra. A especificidade do DNA dos papilomavírus equinos foi avaliada por sequenciamento gênico direto, que confirmou a especificidade dos produtos. A metodologia de PCR proposta possibilita o diagnóstico dos EcPV3, 4, 5 e 6 em amostras FFPE de placa aural equina.(AU)

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A placa aural é uma dermatopatia associada à quatro Equus caballus papillomavirus (EcPVs). Até o momento, o DNA de EcPVs não foi identificado em amostras de placa aural fixadas em formalina e embebidas em parafina (FFPE). O objetivo deste estudo foi otimizar um método para a detecção dos quatro tipos de EcPVs em 21 amostras FFPE usando a PCR. O DNA dos EcPVs foram detectados em 11 amostras (52.4%). O DNA do EcPV4 foi detectado em 38.1% (8/21) e do EcPV3 em 4.8% (1/21) das amostras. Coinfecção foi identificada em duas amostras (9.5%); EcPV4 e 5 foram detectados simultaneamente em uma amostra, enquanto o DNA dos EcPV4 e 6 foi detectado em outra. A especificidade do DNA dos papilomavírus equinos foi avaliada por sequenciamento gênico direto, que confirmou a especificidade dos produtos. A metodologia de PCR proposta possibilita o diagnóstico dos EcPV3, 4, 5 e 6 em amostras FFPE de placa aural equina.(AU)

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BACKGROUND: A community-based randomized trial was conducted in Costa Rica to evaluate the HPV-16/18 AS04-adjuvanted vaccine (NCT00128661). The primary objective was to evaluate efficacy of the vaccine to prevent cervical intraepithelial neoplasia 2 or more severe disease (CIN2+) associated with incident HPV-16/18 cervical infections. Secondary objectives were to evaluate efficacy against CIN2+ associated with incident cervical infection by any oncogenic HPVs and to evaluate duration of protection against incident cervical infection with HPV-16/18. Vaccine safety and immunogenicity over the 4-year follow-up were also evaluated. METHODS: We randomized (3727 HPV arm; 3739 control arm), vaccinated (HPV-16/18 or Hepatitis A) and followed (median 53.8 months) 7466 healthy women aged 18-25 years. 5312 women (2635 HPV arm; 2677 control arm) were included in the according to protocol analysis for efficacy. The full cohort was evaluated for safety. Immunogenicity was considered on a subset of 354 (HPV-16) and 379 (HPV-18) women. HPV type was assessed by PCR on cervical specimens. Immunogenicity was assessed using ELISA and inhibition enzyme immunoassays. Disease outcomes were histologically confirmed. Vaccine efficacy and 95% confidence intervals (95%CI) were computed. RESULTS: Vaccine efficacy was 89.8% (95% CI: 39.5-99.5; N=11 events total) against HPV-16/18 associated CIN2+, 59.9% (95% CI: 20.7-80.8; N=39 events total) against CIN2+ associated with non-HPV-16/18 oncogenic HPVs and 61.4% (95% CI: 29.5-79.8; N=51 events total) against CIN2+ irrespective of HPV type. The vaccine had an acceptable safety profile and induced robust and long-lasting antibody responses. CONCLUSIONS: Our findings confirm the high efficacy and immunogenicity of the HPV-16/18 vaccine against incident HPV infections and cervical disease associated with HPV-16/18 and other oncogenic HPV types. These results will serve as a benchmark to which we can compare future findings from the ongoing extended follow-up of participants in the Costa Rica trial. TRIAL REGISTRATION: Registered with clinicaltrials.gov: NCT00128661.

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Introducción: El cáncer de cuello uterino es una patología prevalente más aun en países sub-desarrollados y existe una relación causal entre la infección persistente con algún tipo oncogénico de HPV y el desarrollo de dicha neoplasia.Se cuenta con un estudio de screening mundialmente aceptado y que también previene el carcinoma cervical que es el Papanicolaou y colposcopia, y en los últimos años se han incorporado estudios de biología molecular para el estudio del ADN viral.Material y Métodos: Se estudiaron a 60 pacientes. Se tomo como método gold standard a la biopsia de cuello uterino y a 29 pacientes se les realizo PCR para identificar ADN-HPV. La edad promedio de las pacientes fue de 30,95 años con mayor cantidad de pacientes en el rango etareo de 21-25 años. Resultados: El 70% tuvo citología negativa y 48 pacientes tuvieron biopsia positiva, 16 con resultado positivo de PCR. Obtuvimos una alta especificidad el Papanicolaou con respecto a la biopsia (90%), no así en comparación con el test de PCR (S=56% E=50%) debido al número pequeño de pacientes que se sometieron a este estudio. Discusión: Las mujeres menores de 30 años son las que más chances tienen de contraer la infección, no así de desarrollar la enfermedad debido a la historia natural de la misma, por lo que aconsejamos continuar con el screening regular de Papanicolaou/colposcopia e introducir con lapsos de 3 años o más en mujeres mayores a 30 años los estudios de biología molecular.Conclusiones: Se espera poder contar con mayores estrategias que nos permitan usar los beneficios de los test ADN-HPV sin sobre tratar a mujeres que probablemente atraviesan por una infección transitoria.

Introduction: Cervical cancer is a prevalent pathology, especially in underdeveloped countries, and there is a causal relationship between persistent infection with some type of oncogenic HPVs and the development of said neoplasia. There are two universally-accepted screening studies which also prevent cervical cancer, i.e. Pap smear and colposcopy, and, in the last few years some molecular biology studies have been adopted for the study of viral DNA. Material and methods: 60 patients were studied. Cervical biopsy was the gold standard method used and 29 patients were tested using the PCR technique to identify HPV-DNA. Patients' average age was 30.95, most of whom belonged to the 21-25 years old age span. Results: 70% of patients had negative cytology test and 48 patients obtained positive biopsy results, 16 had positive results in the PCR test. The Pap smear specificity was higher as regards the biopsy (90%), unlike the PCR test (S=56% E=50%) due to the small number of patients that underwent this study. Discussion: Women younger than 30 years old have more chances of infection, but no of developing the disease considering its natural history. Therefore, we recommend continuing with the Pap smear/colposcopy regular screening and introducing molecular biology studies in women older than 30 years old, every 3 years or more.Conclusions: We hope to have more strategies available which enable the use of HPV-DNA test benefits, without overtreating patients who are probably suffering from a transitory infection.

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Introducción: El cáncer de cuello uterino es una patología prevalente más aun en países sub-desarrollados y existe una relación causal entre la infección persistente con algún tipo oncogénico de HPV y el desarrollo de dicha neoplasia.Se cuenta con un estudio de screening mundialmente aceptado y que también previene el carcinoma cervical que es el Papanicolaou y colposcopia, y en los últimos años se han incorporado estudios de biología molecular para el estudio del ADN viral.Material y Métodos: Se estudiaron a 60 pacientes. Se tomo como método gold standard a la biopsia de cuello uterino y a 29 pacientes se les realizo PCR para identificar ADN-HPV. La edad promedio de las pacientes fue de 30,95 años con mayor cantidad de pacientes en el rango etareo de 21-25 años. Resultados: El 70% tuvo citología negativa y 48 pacientes tuvieron biopsia positiva, 16 con resultado positivo de PCR. Obtuvimos una alta especificidad el Papanicolaou con respecto a la biopsia (90%), no así en comparación con el test de PCR (S=56% E=50%) debido al número pequeño de pacientes que se sometieron a este estudio. Discusión: Las mujeres menores de 30 años son las que más chances tienen de contraer la infección, no así de desarrollar la enfermedad debido a la historia natural de la misma, por lo que aconsejamos continuar con el screening regular de Papanicolaou/colposcopia e introducir con lapsos de 3 años o más en mujeres mayores a 30 años los estudios de biología molecular.Conclusiones: Se espera poder contar con mayores estrategias que nos permitan usar los beneficios de los test ADN-HPV sin sobre tratar a mujeres que probablemente atraviesan por una infección transitoria. (AU)

Introduction: Cervical cancer is a prevalent pathology, especially in underdeveloped countries, and there is a causal relationship between persistent infection with some type of oncogenic HPVs and the development of said neoplasia. There are two universally-accepted screening studies which also prevent cervical cancer, i.e. Pap smear and colposcopy, and, in the last few years some molecular biology studies have been adopted for the study of viral DNA. Material and methods: 60 patients were studied. Cervical biopsy was the gold standard method used and 29 patients were tested using the PCR technique to identify HPV-DNA. Patients average age was 30.95, most of whom belonged to the 21-25 years old age span. Results: 70% of patients had negative cytology test and 48 patients obtained positive biopsy results, 16 had positive results in the PCR test. The Pap smear specificity was higher as regards the biopsy (90%), unlike the PCR test (S=56% E=50%) due to the small number of patients that underwent this study. Discussion: Women younger than 30 years old have more chances of infection, but no of developing the disease considering its natural history. Therefore, we recommend continuing with the Pap smear/colposcopy regular screening and introducing molecular biology studies in women older than 30 years old, every 3 years or more.Conclusions: We hope to have more strategies available which enable the use of HPV-DNA test benefits, without overtreating patients who are probably suffering from a transitory infection. (AU)

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Infection with high risk Human papillomavirus (HR-HPV) is necessary but not sufficient to cause cervical carcinoma. This study explored whether multiple HR-HPV or coinfection with Epstein-Barr virus (EBV) influence the integration status of HPV16 genome. The presence and typing of HPV in a series of 125 cervical specimens were assessed by polymerase chain reaction (PCR) using the specific primers for the HPV L1 region. As for EBV infection, the viral EBNA1 gene was used for its detection through PCR amplification. Disruption of the HPV E2 gene was assessed by amplification of the entire E2 gene with single set of primers, while E2 transcripts were evaluated by a reverse transcription PCR method (RT-PCR). The overall prevalence of HPVDNA was of 81.8% in cervical cancers versus 26.9% in benign lesions. In HPV positive cases, HPV16 and HPV18 were the most prevalent types, followed by HPV types 33, 31. EBV EBNA1 prevalence was statistically more frequent in cervical carcinomas than in benign lesions (29.5%, vs 9.6%; P=0.01). No viral infection was detected in healthy control women. The uninterrupted E2 gene was correlated with the presence of E2 transcripts originating from the HPV episomal forms. It was observed that integration was more common in HPV18 and EBV coinfection. The presence of EBV caused a five-fold [OR= 5; CI= 1.15-21.8; P = 0.04] increase in the risk of HPV16 genome integration in the host genome. This study indicates that EBV infection is acting as a cofactor for induction of cervical cancer by favoring HPVDNA integration.

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Infection with high risk Human papillomavirus (HR-HPV) is necessary but not sufficient to cause cervical carcinoma. This study explored whether multiple HR-HPV or coinfection with Epstein-Barr virus (EBV) influence the integration status of HPV16 genome. The presence and typing of HPV in a series of 125 cervical specimens were assessed by polymerase chain reaction (PCR) using the specific primers for the HPV L1 region. As for EBV infection, the viral EBNA1 gene was used for its detection through PCR amplification. Disruption of the HPV E2 gene was assessed by amplification of the entire E2 gene with single set of primers, while E2 transcripts were evaluated by a reverse transcription PCR method (RT-PCR). The overall prevalence of HPVDNA was of 81.8% in cervical cancers versus 26.9% in benign lesions. In HPV positive cases, HPV16 and HPV18 were the most prevalent types, followed by HPV types 33, 31. EBV EBNA1 prevalence was statistically more frequent in cervical carcinomas than in benign lesions (29.5%, vs 9.6%; P=0.01). No viral infection was detected in healthy control women. The uninterrupted E2 gene was correlated with the presence of E2 transcripts originating from the HPV episomal forms. It was observed that integration was more common in HPV18 and EBV coinfection. The presence of EBV caused a five-fold [OR= 5; CI= 1.15-21.8; P = 0.04] increase in the risk of HPV16 genome integration in the host genome. This study indicates that EBV infection is acting as a cofactor for induction of cervical cancer by favoring HPVDNA integration.

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Infection with high risk Human papillomavirus (HR-HPV) is necessary but not sufficient to cause cervical carcinoma. This study explored whether multiple HR-HPV or coinfection with Epstein-Barr virus (EBV) influence the integration status of HPV16 genome. The presence and typing of HPV in a series of 125 cervical specimens were assessed by polymerase chain reaction (PCR) using the specific primers for the HPV L1 region. As for EBV infection, the viral EBNA1 gene was used for its detection through PCR amplification. Disruption of the HPV E2 gene was assessed by amplification of the entire E2 gene with single set of primers, while E2 transcripts were evaluated by a reverse transcription PCR method (RT-PCR). The overall prevalence of HPVDNA was of 81.8% in cervical cancers versus 26.9% in benign lesions. In HPV positive cases, HPV16 and HPV18 were the most prevalent types, followed by HPV types 33, 31. EBV EBNA1 prevalence was statistically more frequent in cervical carcinomas than in benign lesions (29.5%, vs 9.6%; P=0.01). No viral infection was detected in healthy control women. The uninterrupted E2 gene was correlated with the presence of E2 transcripts originating from the HPV episomal forms. It was observed that integration was more common in HPV18 and EBV coinfection. The presence of EBV caused a five-fold [OR= 5; CI= 1.15-21.8; P = 0.04] increase in the risk of HPV16 genome integration in the host genome. This study indicates that EBV infection is acting as a cofactor for induction of cervical cancer by favoring HPVDNA integration.

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Este artigo refere-se a uma revisão de literatura sobre o vírus HPV e câncer de colo de útero, com o objetivo de levantar aspectos da infecção do vírus que influenciam no curso natural do câncer de colo de útero tais como: a tipologia do vírus, a duração e a persistência da infecção além de associar com as manifestações das lesões precursoras até a evolução da neoplasia. Foi possível constatar a forte associação da infecção com a evolução da neoplasia cervical, no entanto, ainda são necessários estudos que elucidem melhor certos aspectos da infecção do vírus HPV que agem sobre o colo do útero para que as ações de prevenção e combate a doença sejam mais eficazes.

This article refers to a review of literature about the HPV virus and the cervical neoplasia, aiming at raising aspects of the virus infection which influences in the natural development of the uterine cervical cancer such as: the type of virus, the duration and the persistence of the infection and also the association with the manifestations of the preceding lesions up to the evolution of the neoplasia. It was possible to notice the strong association of the infection with the evolution of the cervical neoplasia, however, studies to better elucidate certain aspects of the infection of the HPV virus that acts on the uterine cervix are still necessary so that the actions of prevention and fight against the disease will be more efficient.

Este artículo se refiere a una revisión de literatura sobre el virus HPV y la neoplasia cervical, con el objetivo de levantar aspectos de la infección del virus que influye en el curso natural del cáncer de cuello del útero tales como: la tipologia del virus, la duración y la persistencia de la infección además de asociarlo a las manifestaciones de las lesiones precursoras hasta la evolución de la neoplasia. Ha sido posible constatar la fuerte asosiación de la infección con la evolución de la neoplasia cervical, entretanto, aún son necesarios estudios que eluciden mejor ciertos aspectos de la infección del virus HPV que actúa sobre el cuello del útero para que las acciones de prevención y combate a la enfermedad sean más eficaces.

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Por meio da descrição de dois casos, os autores visam chamar a atenção para a forma de apresentação do condiloma imaturo ou metaplasia papilar imatura atípica (MPIA), assim como para as dificuldades de detecção citológica, classificação histológica e interpretação adequada. As características do condiloma imaturo ao colposcópio e na cervicografia foram relacionadas com seu aspecto histopatológico e com o padrão colposcópico do condiloma acuminado típico cervical. Exames citopatológicos resultaram negativos ou com células escamosas atípicas de significado indeterminado (ASCUS). Em um dos casos foi realizada captura híbrida para papilomavírus humano (HPV), que identificou tipos virais de alto e baixo graus. A partir do estudo dos casos concluiu-se que: a) o condiloma imaturo pode ser identificado por exame colposcópico ou cervicográfico, podendo ser precedido ou acompanhado do diagnóstico citológico de ASCUS ou detecção de HPV por teste molecular; b) a caracterização histopatológica dessas lesões como de baixo grau evita o tratamento cirúrgico desnecessário.

Based on the report of two cases, we aim to highlight the presentation of immature condyloma or atypical papillary immature metaplasia (AIM) as well as the difficulties in its cytological detection, histopathological classification and accurate interpretation of results. The colposcopic and cervicographic characteristics of the immature condyloma were related to its histopathological features and the colposcopic standard of acuminated condyloma. Cytopathological exam results were negative or presented atypical squamous cells of undetermined significance (ASCUS). In one case, a hybrid capture test for human papillomavirus (HPV) was carried out, what identified viral types of high and low grades. The study concluded that: 1) immature condylomas may be identified by means of colposcopic or cervicographic exam, and may be preceded or followed by a cytological diagnosis for ASCUS or HPV detection using molecular test; 2. histopathological characterization of these lesions as low grade avoids unnecessary surgical treatment.

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El virus de polioma es capaz de inducir tumores en sus hospederos naturales y transformar células en cultivo. Por otro lado, el virus de papiloma humano se ha relacionado con diversos tipos de neoplasias; de manera particular con lesiones anogenitales humanas. No se conoce con exactitud el mecanismo a través del cual estos virus inducen transformación y tumorigénesis. El presente trabajo muestra algunas de las características de los mecanismos que utilizan los virus mencionados para participar en la transformación y tumorigénesis. Además, se ha encontrado que ciertos aspectos de la infección por el virus de polioma son parecidos a la infección del virus del papiloma (ambos pertenecen a la misma familia Papovaviridae), por lo que se consideran algunas semejanzas y diferencias entre los mismos

Polyomavirus is able to induce tumors in its natural host as well as to transform cells in cultures. On the other hand, human papillomavirus has been involved in several types of neoplasias such as anogenital lesions. Little is known about the mechanisms through which these viruses induce both transformation and tumorigenesis. The present work shows some characteristics of the mechanisms that papillomavirus and polyomavirus use to participate in tumorigenesis. It has also been noticed that the infection caused by polyomavirus resembles that performed by papillomaviruses (which belong to the same Papovaviridae family). Some similarities and differences between these viruses are considered.

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