Combined Oral Contraceptive Use and the Risk of Cervical Cancer: Literature Review / Uso de anticoncepcional oral combinado e o risco de câncer cervical: Revisão da literatura

Abstract Cervical cancer (CC) is caused by persistent infection of human papillomavirus of high oncogenic risk (hr-HPV); however, several cofactors are important in its carcinogenesis, such as smoking, multiparity, and prolonged use of oral hormonal contraceptives (COCs). Worldwide, 16% of women use COCs, whereas in Brazil this rate is of ~ 30%. The safety and adverse effects of COCs are widely discussed in the literature, including the increase in carcinogenic risk. Due to the existence of several drugs, combinations, and dosages of COCs, it is hard to have uniform information in epidemiological studies. Our objective was to perform a narrative review on the role of COCs use in the carcinogenesis of cervical cancer. Several populational studies have suggested an increase in the incidence of cervical cancer for those who have used COCs for > 5 years, but other available studies reach controversial and contradictory results regarding the action of COCs in the development of CC.

Resumo O câncer cervical (CC) é causado pela infecção persistente pelo papilomavírus humano de alto risco oncogênico (hr-HPV); entretanto, vários cofatores são importantes na sua carcinogênese, como tabagismo, multiparidade e uso prolongado de contraceptivos hormonais orais (COCs). No mundo, 16% das mulheres usam AOCs, enquanto no Brasil essa taxa é de ~ 30%. A segurança e os efeitos adversos dos COCs são amplamente discutidos na literatura, incluindo o aumento do risco carcinogênico. Devido à existência de várias drogas, combinações e dosagens de COCs, é difícil ter informações uniformes em estudos epidemiológicos. Nosso objetivo foi realizar uma revisão narrativa sobre o papel do uso de COCs na carcinogênese do câncer cervical. Vários estudos populacionais têm sugerido aumento da incidência de câncer de colo uterino para aquelas que usam COCs há mais de 5 anos, mas outros estudos disponíveis chegam a resultados controversos e contraditórios quanto à ação dos COCs no desenvolvimento do CCU.

A autonomia do adolescente em relação ao direto de imunização contra infecções sexualmente transmissíveis: revisão bibliográfica / La autonomía de los adolescentes en relación con la inmunización directa contra las infecciones de transmisión sexual: revisión bibliográfica / The autonomy of adolescents in relation to the direct of immunization against sexually transmitted infections: bibliographic review

O presente estudo trata-se de uma análise na literatura sobre o aspecto bioético da autonomia em relação a imunização contra Hepatite B e HPV na adolescência. Foi realizada uma revisão bibliográfica baseada no método prisma onde foram incluídos artigos em português e inglês os quais foram pesquisados nas plataformas Scientific Electronic Library Online (SciELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e National Library of Medicine (PUBMED), utilizando os seguintes descritores Hepatitis B Vaccines, bioethics, Humans. Os resultados demostraram a eficiência dos profissionais de saúde no contato com o indivíduo e o convencimento deste através de um diálogo aberto e criação de vínculos. Evidenciou-se ainda o estudo evidenciou o direito a autonomia progressiva do paciente, no qual este ganha o direito a algumas escolhas como as imunizações de doenças sexualmente transmissíveis, como é o caso da Hepatite B e HPV, no entanto é necessário que o adolescente seja instruído sobre a imunização. Assim sendo, reconhece-se o direito a autonomia progressiva do adolescente, referente a escolha das imunizações contra a Hepatite B e HPV, entretanto, deve-se considerar que estes indivíduos sejam instruídos sobre os benefícios individuais e/ou coletivos da vacinação, contemplados por atividades de educação em saúde por profissionais qualificados, objetivando ampliar a cobertura global de imunização com doenças que caracterizam problemas de saúde pública.

El presente estudio es un análisis de la literatura sobre el aspecto bioético de la autonomía en relación con la inmunización contra la Hepatitis B y el VPH en la adolescencia. Se realizó una revisión bibliográfica basada en el método del prisma, que incluyó artículos en portugués e inglés que fueron buscados en la Biblioteca Científica Electrónica en Línea (SciELO), Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS) y la Biblioteca Nacional de Medicina (PUBMED), utilizando los siguientes descriptores Vacunas Hepatitis B, bioética, Humanos. Los resultados demostraron la eficiencia de los profesionales de la salud en contactar al individuo y convencerlo a través de un diálogo abierto y creación de vínculos. También se evidenció que el estudio evidenció el derecho del paciente a la autonomía progresiva, en la que adquiere el derecho a algunas opciones como las inmunizaciones de enfermedades de transmisión sexual, como la Hepatitis B y el VPH, sin embargo, es necesario que el adolescente sea educado sobre la inmunización. Por lo tanto, se reconoce el derecho del adolescente a la autonomía progresiva, en cuanto a la elección de las vacunas contra la Hepatitis B y el VPH, sin embargo, se debe considerar que estos individuos sean educados sobre los beneficios individuales y/o colectivos de la vacunación, contemplados por las actividades de educación en salud por profesionales calificados, con el objetivo de ampliar la cobertura mundial de inmunización con enfermedades que caracterizan los problemas de salud pública.

The present study is an analysis of the literature on the bioethical aspect of autonomy in relation to immunization against Hepatitis B and HPV in adolescence. A bibliographic review was carried out based on the prism method, which included articles in Portuguese and English which were searched on the Scientific Electronic Library Online (SCIELO), Latin American and Caribbean Literature on Health Sciences (LILACS) and the National Library of Medicine (PUBMED), using the following descriptors Hepatitis B Vaccines, bioethics, Humans. The results demonstrated the efficiency of health professionals in contacting the individual and convincing him/her through an open dialogue and creation of bonds. It was also evidenced the study evidenced the patient's right to progressive autonomy, in which he gains the right to some choices such as immunizations of sexually transmitted diseases, such as Hepatitis B and HPV, however it is necessary for the adolescent to be educated about immunization. Therefore, the adolescent's right to progressive autonomy is recognized, regarding the choice of immunizations against Hepatitis B and HPV, however, it must be considered that these individuals are instructed on the individual and/or collective benefits of vaccination, contemplated by health education activities by qualified professionals, aiming to expand the global coverage of immunization with diseases that characterize public health problems.

HPV vaccination programs in LMIC: is it time to optimize schedules and recommendations?

Abstract Objectives: 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 uterine cervix, vulva, vagina, penis, and anal canal. Moreover, two of the vaccines prevent the occurrence 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 adherence of the target population.

Evaluation of variable p16 immunostaining patterns, Ki-67 indices and HPV status in cervical SILs and squamous cell carcinomas: An institutional experience

Objective: The present study evaluates the immunoexpression of p16 and Ki-67 in cervical squamous intraepithelial lesion (SIL) and carcinomas and correlates their expression with clinicopathological features and HPV-DNA status. Material and Methods: A total 36 included cases of SIL and squamous cell carcinoma (SCC) were subjected to p16 and Ki-67 immunostaining. p16 staining was evaluated depending on grading, distribution, localization pattern, intensity and IHC score. Ki-67 expression was graded based on percentage of positive cells. Results: Incidence of HSIL and SCC cases was found to be significantly increased with parity > 5. p16 grade III diffuse nucleocytoplasmic immunostaining was observed in 62.5% LSIL, 80% HSIL and 87% SCC cases. Significant association of p16 staining intensity, IHC score and Ki-67 indices was noted with increasing grades of SILs and carcinomas. Conclusion: Our experience indicates that a combination of p16 and Ki-67 immunostaining may be useful to determine the severity of dysplastic change.

Prevalence of HPV infection and cervical intraepithelial lesions in HIV positive and negative women in the city of Florianopolis / Prevalência da infecção pelo HPV e lesões intraepiteliais cervicais em mulheres HIV positivas e negativas na cidade de Florianópolis

Introduction: HPV infection is the most frequent sexually transmitted infection in women. The high oncogenic risk HPV, associated with others factors, there are a risk of progressing to a precancerous lesion of the cervix and even cancer. This evolution is related to the persistence of the infection and other factors, mainly those that interfere with the woman's immunity. The immunosuppression caused by HIV infection is an important factor for viral persistence and the appearance of these lesions. Objectives: To compare the prevalence of HPV infection and cervical intraepithelial lesions in HIV-positive and negative women and describe the possible associated risk factors. Methods: The sample consisted of 50 HIV positive women (study group) and 50 HIV negative women (control group) recruited from the public health system of Florianópolis during the months of January to April 2022. Cervical samples were collected for cytological analysis and for detection of high-risk oncogenic HPV DNA by polymerase chain reaction (PCR). Categorical variables were compared using the chi-square test, with a significance level set at 5% Results: HPV infection was more prevalent in the control group, however, HIV positive women had a higher frequency of intraepithelial lesions diagnosed on cytology. Factors such as greater number of sexual partners, depression and smoking were more frequent in the group of HIV positive women. The number of CD4 T cells less than 200 cels/mm3 was associated with a higher number of altered Pap smears and a positive HPV DNA test. The use of combination antiretroviral therapy and undetectable viral load were associated with a greater number of normal cytology and undetected HPV DNA. Conclusion: The prevalence of cervical intraepithelial lesions in HIV-infected women is higher than in women without infection. The presence of HIV infection was the most important risk factor associated with the development of cervical lesions. (AU)

Introdução: O Papilomavírus Humano (HPV) é a infecção de transmissão sexual mais frequente na mulher. O HPV de alto risco oncogênico, associado a outros fatores, apresenta risco de evoluir para uma lesão pré-cancerosa do colo de útero e até mesmo para o câncer. Essa evolução está relacionada à persistência da infecção e outros fatores, principalmente os que interferem na imunidade da mulher. A imunossupressão causada pela infecção HIV é um fator importante para a persistência viral e o aparecimento destas lesões. Objetivos: Comparar a prevalência da infecção pelo HPV e das lesões intraepiteliais do colo de útero em mulheres HIV positivas e negativas, e descrever os possíveis fatores de risco associados. Métodos: A amostra foi composta por 50 mulheres HIV positivas (grupo de estudo) e 50 mulheres HIV negativas (grupo controle) recrutadas no sistema público de saúde de Florianópolis durante os meses de janeiro a abril de 2022. Foram coletadas amostras cervicais para análise citológica e para detecção do DNA HPV de alto risco oncogênico por reação em cadeia da polimerase (PCR). As variáveis categóricas foram comparadas pelo teste qui-quadrado, com nível de significância estabelecido em 5%. Resultados: A infecção pelo HPV foi mais prevalente no grupo controle, entretanto, as mulheres HIV positivas tiveram uma maior frequência de lesões intraepiteliais diagnosticadas na citologia. Os fatores como maior número de parceiros sexuais, depressão e tabagismo foram mais frequentes no grupo de mulheres HIV positivas. O número de células TCD4 inferior a 200 células/mm3 esteve associado a maior número de colpocitologias alteradas e teste DNA HPV positivo. O uso da terapia antirretroviral combinada e a carga viral indetectável estiveram associadas a um número elevado de citologias normais e DNA HPV não detectado. Conclusão: A prevalência de lesões intraepiteliais do colo do útero em mulheres infectadas pelo HIV foi maior que em mulheres soronegativas. A presença de infecção pelo HIV foi o fator de risco mais importante associado ao desenvolvimento de lesões cervicais.Palavras-chave: HPV. HIV. coinfecção. lesões intraepiteliais escamosas cervicais. prevalência.. (AU)

Genital Human Papillomavirus Infection in women from Florianópolis - Santa Catarina, Brazil / Infecção genital pelo Papilomavírus Humano em mulheres de Florianópolis - Santa Catarina, Brasil

Introduction: Human Papillomavirus (HPV) infection is the most common sexually transmitted infection in women. About 80% of sexually active women will have contact with this virus at some age in their lives. Most infections will be transient, but when the infection becomes persistent, associated with high oncogenic risk HPV, there may be progression to cancer, especially cervical cancer. The best way to prevent HPV infection is through the use of vaccines. Objective: To assess which are the most prevalent types of HPV in the city of Florianópolis, Brazil and if the majority of the diagnosed types are contained in the HPV vaccines currently available on the market and in the public health sector. Methods: More than 14,727 HPV tests were evaluated for the diagnosis of genital HPV infection in women from Florianópolis. The prevalence of infection was evaluated according to age of the women. HPV detection was performed using molecular biology tests, such as hybrid capture (for diagnosis of the HPV group, high or low oncogenic risk) and PCR (viral genotyping) techniques. Results: The diagnosis of HPV infection was made for women between one and 102 years of age. The highest positivity of the exams was observed in women aged 20­25 years (51% of the exams). The most prevalent age group was 31­35 years old (23.5%), and the lowest was for women aged 70 and above (0.6%). High oncogenic risk HPV was detected in 94.1% of positive samples and was the most frequent in all age groups. Mixed infection (high- and low-risk HPV) was more prevalent in the 66­70 age group (25.6%). The most frequent genotypes were non-16/18 high oncogenic risk HPV (77% of positive cases). HPV 16 was found in 17.1% of positive cases, and HPV 18 in 6.5%. Conclusion: The most prevalent types of HPV in Florianópolis in the last 6 years are non-16/18 high oncogenic risk HPV types, viral types not covered by the current HPV vaccine available in the public health sector in Brazil.

Introdução: A infecção pelo Papilomavírus Humano (HPV)é a infecção sexualmente transmissível mais frequente na mulher. Cerca de 80% das mulheres sexualmente ativas irão entrar em contato com este vírus em algum momento da sua vida. A maioria das infecções será transitória, mas quando a infecção se torna persistente, associada aos HPV de alto risco oncogênico, poderá haver a progressão para o câncer, principalmente o câncer de colo de útero. A melhor forma de prevenção da contaminação pelo HPV é através da utilização das vacinas. Objetivo: Avaliar quais são os tipos de HPV mais prevalentes na cidade de Florianópolis, Brasil, e se a maioria dos tipos diagnosticados estão contidos nas vacinas contra o HPV atualmente disponíveis no mercado e no setor público de saúde. Métodos: Foram avaliados 14.727 exames para diagnóstico da infecção genital pelo HPV em mulheres de Florianópolis, de acordo com a idade das mulheres. A detecção do HPV foi realizada através dos exames de biologia molecular pelas técnicas de captura híbrida (para diagnóstico do grupo de HPV, alto ou baixo risco oncogênico) e PCR (genotipagem viral). Resultados: Foram avaliados exames para diagnóstico da infecção de mulheres entre um e 102 anos de idade. A maior positividade dos exames foi observada em mulheres dos 20­25 anos (51% dos exames). A faixa etária de maior prevalência foi dos 31­35 anos (23,5%), e a menor, após os 70 anos (0,6%). O HPV de alto risco oncogênico foi detectado em 94,1% dos casos positivos e foi o mais frequente em todas as faixas etárias. A infecção mista (HPV de alto e baixo risco) foi mais prevalente na faixa etária dos 66­70 anos (25,6%). Os genótipos mais frequentes foram os HPV de alto risco oncogênico não 16/18 (77% dos casos positivos). O HPV 16 foi encontrado em 17,1% dos casos positivos, e o HPV 18 em 6,5%. Conclusão: Os tipos de HPV mais prevalentes em Florianópolis nos últimos 6 anos são os HPV de alto risco oncogênico não 16/18, tipos virais não cobertos pela atual vacina contra o HPV disponível no setor público de saúde do Brasil.Palavras-chave: HPV. Tipos de HPV. Câncer de colo de útero. Cobertura vacinal.

Epidemiological surveillance of Human Papillomavirus (HPV) genotypes in oral and genital tracts and the impact of HPV vaccination on male university students from Rio de Janeiro state, Brazil / Vigilância Epidemiológica dos genótipos de papilomavírus humano (HPV) nos tratos oral e genital e o impacto da vacinação em estudantes universitários do sexo masculino do estado do Rio de Janeiro, Brasil

Introduction: Human Papillomavirus (HPV) infections are of significant concern in men, given its potential impact on their health and the risk of transmission to partners. Understanding and addressing this infection in men is crucial to evaluate the effectiveness of vaccination in reducing HPV-related diseases. Objective: To assess the impact of HPV vaccination, potential genotype shifts, and adverse effects, through a prospective study conducted with male university students. Methods:The study involved 286 volunteers who were examined at Sexually Transmitted Disease Clinics at the Universidade Federal Fluminense in Niterói, Rio de Janeiro, Brazil. The HPV prevalence was evaluated using generic PCR, genotyped by DNA microarray and monitored adverse effects. Results: The findings of this study revealed the absence of moderate or severe adverse effects. Genetic shifts were observed, including the disappearance of oncogenic HPV types 16 and 18. Surprisingly, even after completing the full vaccine regimen, students still harbored HPV11 in the oral tract. Furthermore, persistent HPV 6 and 11 infections were identified in three students, who had pre-existing infections prior to vaccination, at the follow-up visit. Multivariate analysis uncovered independent associations, notably an increased risk of HPV infection in the oral tract among men who have sex with men. HPV prevalence rates remained low both before and after the vaccination scheme (T0: 14.7%, T1: 8.7%). Even after the full vaccination scheme, the prevalence remained similar at T2 (14.6%), with no statistically significant differences recorded. HPV11 emerged as the most prevalent type throughout the study, followed by HPV6. Vaccine genotypes were detected in a significant proportion of samples at T0 (85.4%), T1 (89.5%), and T2 (100%). Conclusion: Overall, this study suggests that vaccination may represent a promising approach to reducing HPV-related health risks. These findings shed light on the potential benefits and challenges of HPV vaccination, emphasizing the need for continued monitoring and vaccination efforts

Introdução: As infecções por papilomavírus humano (HPV) são de grande preocupação em homens, dada sua possível influência na saúde deles e no risco de transmissão para parceiros. Compreender e abordar essa infecção em homens é fundamental para avaliar a eficácia da vacinação na redução de doenças relacionadas ao HPV. Objetivo: Avaliar o impacto da vacinação contra o HPV, possíveis alterações genotípicas e efeitos adversos, por meio de um estudo prospectivo realizado em estudantes universitários do sexo masculino. Métodos: O estudo envolveu 286 voluntários examinados em Clínicas de Doenças Sexualmente Transmissíveis na Universidade Federal Fluminense, em Niterói, Rio de Janeiro, Brasil. A prevalência do HPV foi avaliada por polymerase chain reaction (PCR) genérico e genotipada por microarranjo de DNA, e foram monitorados os efeitos adversos. Resultados: Os resultados deste estudo revelaram a ausência de efeitos adversos moderados ou graves. Observaram-se mudanças genéticas, incluindo o desaparecimento dos tipos oncogênicos do HPV 16 e 18. Surpreendentemente, mesmo após a conclusão do esquema completo de vacinação, os estudantes ainda abrigavam o HPV 11 na cavidade oral. Além disso, foram identificadas infecções persistentes pelo HPV 6 e 11 em três estudantes que já tinham infecções preexistentes antes da vacinação e na visita de acompanhamento. A análise multivariada revelou associações independentes, especialmente um aumento no risco de infecção pelo HPV na cavidade oral em homens que têm relações sexuais com homens. As taxas de prevalência do HPV permaneceram baixas tanto antes quanto depois do esquema de vacinação (T0: 14,7%, T1: 8,7%). Mesmo após a conclusão do esquema de vacinação, a prevalência permaneceu semelhante em T2 (14,6%), sem diferenças estatisticamente significativas registradas. O HPV 11 emergiu como o tipo mais prevalente ao longo do estudo, seguido pelo HPV 6. Genótipos da vacina foram detectados em uma proporção significativa de amostras em T0 (85,4%), T1 (89,5%) e T2 (100%). Conclusão: No geral, este estudo sugere que a vacinação pode representar uma abordagem promissora para a redução dos riscos à saúde relacionados ao HPV. Esses achados lançam luz sobre os benefícios e desafios potenciais da vacinação contra o HPV, enfatizando a necessidade de monitoramento contínuo e esforços de vacinação

Detection of HPV DNA in vaginal samples self-collected by women living with HIV treated through the Brazilian public health system: Prevalence and analysis of risk factors

ABSTRACT Background: Women living with human immunodeficiency virus (HIV) (WLWH) are more likely to be infected with the oncogenic human papillomavirus (HPV). We assessed the prevalence of high-risk (HR) (16/18/31/33/35/39/45/51/52/56/58/59/68/73/82), probable high-risk (pHR) (26/53/66), and low-risk (LR) (6/11/40/42/43/44/54/61/70) HPV types and their associated risk factors. Methods: This cross-sectional study of WLWH aged 18-64 years included one laboratory and eight HIV-specialty healthcare facilities in the pilot network. Descriptive statistics were used to assess sociodemographic and behavioral characteristics. Adjusted analyses were conducted to evaluate risk factors associated with HR and/or pHR HPV infection in WLWH. Results: From May/2021 to May/2022, 1,914 (92.5%) WLWH participated in the pilot study and had valid HPV-DNA results of self-collected vaginal samples. The median age of the participants was 45 years, 60.1% had ≥ 9 years of schooling, 80.5% were ≤ 18 years at first sexual intercourse, and 51.7% had > 4 sexual partners throughout life. The prevalence of any HPV type, HR HPV, pHR HPV, and LR HPV was 65.8%, 49.6%, 16.7%, and 40.0%, respectively. Age was inversely associated with pHR and/or HR-HPV (p < 0.001), and education level was inversely associated with HR-HPV (p = 0.003) types. Any HR or pHR was associated with being single (p = 0.029) and exchanging sex for drugs (p = 0.037). Conclusions: The prevalence of HPV, especially HR HPV, among WLWH is high in Brazil, highlighting the need for HPV screening in this population. Self-collection of vaginal samples is an important strategy for increasing testing access.

Clarity of publications on HPV in Instagram profiles of official health agencies in Brazil

Abstract The study analyzed the clarity of publications on human papillomavirus (HPV) in the Instagram profiles of official Brazilian health agencies. An infodemiological study analyzed publications on HPV in the 81 Instagram profiles selected from the Health Ministry, States' Health Departments, and dental councils and associations. The following data were collected: classification of content, type of profiles, type of media, how the content was addressed, number of posts, frequency, likes, comments, viewings, and hashtags, and how the HPV vaccine was addressed. The clarity of the educational publications was assessed using the Brazilian version of the Clear Communication Index (BR-CDC-CCI). Data analysis was performed with Spearman's correlation and the Mann-Whitney test (p < 0.05). A total of 504 publications on HPV were found. The average number of likes was 528.3 (SD = 2388.2) and the average BR-CDC-CCI score was 67.1 (SD = 14.1). The quality and clarity of the information was considered adequate (BR-CDC-CCI score ≥ 90) in 6.9% of the publications. A weak positive correlation was found between the number of likes and both the BR-CDC-CCI score (r = 0.195) and number of posts (r = 0.124). Publications from the Health Ministry had a significantly higher BR-CDC-CCI score (72.9) compared to the other profiles analyzed (p = 0.01). Most publications concerned government actions, had low engagement, and written educational information was of low clarity and quality. However, the effort to reach the population was evident, with an increase in publications over the years.

Cervical Cancer Screening with DNA-HPV Testing and Precancerous Lesions Detection: A Brazilian Population-based Demonstration Study / Rastreamento do câncer do colo do útero com teste de DNA-HPV e detecção de lesões precursoras: um estudo de demonstração de base populacional brasileiro

Abstract Objective To evaluate the rates of precancerous lesions, colposcopy referral, and positive predictive value (PPV) by age groups of a population-based screening with DNA-HPV testing. Methods The present demonstration study compared 16,384 HPV tests performed in the first 30 months of the program with 19,992 women tested in the cytology screening. The colposcopy referral rate and PPV for CIN2+ and CIN3+ by age group and screening program were compared. The statistical analysis used the chi-squared test and odds ratio (OR) with 95% confidence interval (95%CI). Results The HPV tests were 3.26% positive for HPV16-HPV18 and 9.92% positive for 12 other HPVs with a 3.7 times higher colposcopy referral rate than the cytology program, which had 1.68% abnormalities. Human Papillomavirus testing detected 103 CIN2, 89 CIN3, and one AIS, compared with 24 CIN2 and 54 CIN3 detected by cytology (p < 0.0001). The age group between 25 and 29 years old screened by HPV testing had 2.4 to 3.0 times more positivity, 13.0% colposcopy referral, twice more than women aged 30 to 39 years old (7.7%; p < 0.0001), and detected 20 CIN3 and 3 early-stage cancer versus 9 CIN3 and no cancer by cytology screening (CIN3 OR= 2.10; 95%CI: 0.91 -5.25; p = 0.043). The PPV of colposcopy for CIN2+ ranged from 29.5 to 41.0% in the HPV testing program. Conclusion There was a significant increase in detections of cervix precancerous lesions in a short period of screening with HPV testing. In women < 30 years old, the HPV testing exhibited more positivity, high colposcopy referral rate, similar colposcopy PPV to older women, and more detection of HSIL and early-stage cervical cancer.

Resumo Objetivo Avaliar as taxas de lesões pré-cancerosas, encaminhamento para colposco pia e valor preditivo positivo (VPP) por faixas etárias de rastreamento populacional com teste DNA-HPV. Métodos O presente estudo de demonstração comparou 16.384 testes de HPV realizados nos primeiros 30 meses do programa com 19.992 mulheres testadas no rastreio citológico. Os programas foram comparados por taxa de encaminhamento de colposcopia e VPP para NIC2+ e NIC3+ por faixa etária. A análise estatística utilizou o teste de qui-quadrado e odds ratio (OR, na sigla em inglês) com intervalo de confiança (IC) de 95%. Resultados Os testes de HPV foram 3,26% positivos para HPV16-HPV18 e 9,92% positivos para 12 outros HPVs, com uma taxa de encaminhamento de colposcopia 3,7 vezes maior do que o programa de citologia, que teve 1,68% de anormalidades. O teste de HPV detectou 103 NIC2, 89 NIC3 e um AIS, em comparação com 24 NIC2 e 54 NIC3 detectados por citologia (p < 0,0001 ). O rastreio por teste de HPV no grupo etário 25 a 29 anos teve 2,4 a 3,0 vezes mais positividade, 13,0% de encaminhamento para colposcopia, 2 vezes mais que mulheres de 30 a 39 anos (7,7%; p < 0,0001 ), e detectou 20 NIC3 e 3 cânceres em estágio inicial versus nove NIC3 e nenhum câncer pelo rastreio citológico (NIC3 OR= 2,10; 96%CI: 0,91 -5,25; p = 0,043). O VPP da colposcopia para NIC2+ variou de 29,5 a 41,0% no programa de teste de HPV. Conclusão Houve um aumento significativo na detecção de lesões pré-cancerosas do colo do útero em um curto período de rastreamento com teste de HPV. Em mulheres < 30 anos, o teste de HPV exibiu mais positividade, alta taxa de encaminhamento para colposcopia com VPP semelhante a mulheres mais velhas, e mais detecção de HSIL e de câncer cervical em estágio inicial.

Associação entre lesões de hpv e os carcinomas genitais e da cavidade oral: uma revisão narrativa / Association between hpv lesions and genital and oral cavity carcinomas: a narrative review / Asociación entre lesiones por vph y carcinomas genitales y de cavidad oral: una revisión narrativa

Os Papilomavírus Humano (HPVs) são membros da família Papilomaviridae. O vírus destaca-se pelo seu tropismo por células epiteliais, infectando exclusivamente mucosa epitelial e cutânea. O HPV-16 e HPV-18 são subtipos classificados como de alto risco, conhecidos por sua oncogenicidade, fortemente associados aos cânceres anais, genitais e de orofaringe. Lesões por HPV representam um grande grupo de doenças sexualmente transmissíveis. O objetivo do presente estudo consistiu em realizar uma revisão narrativa sobre a associação entre lesões por HPV e carcinomas genitais e da cavidade oral. Realizamos uma busca na base de dados eletrônicos PubMed, Lilacs, Scielo, Medline e Google Scholar, sendo utilizados artigos publicados entre os anos de 2017-2021, ao fim, foram selecionados 36 artigos. Grande parte das infecções por HPV são subclínicas, ou seja, não apresentam sintomatologia importante e tendem a desaparecer espontaneamente. Desta forma, faz-se necessário ter conhecimento a respeito dos aspectos clínicos e comportamentais dessas lesões, possibilitando o diagnóstico precoce, evitando a evolução para estágios mais invasivos, favorecendo um tratamento efetivo e melhor prognóstico.

Human Papillomaviruses (HPVs) are members of the Papilomaviridae family. The virus stands out for its tropism for epithelial cells, exclusively infecting epithelial and cutaneous mucosa. O HPV-16 and HPV-18 are subtypes classified as high risk, known for their oncogenicity, strongly associated with anal, genital and oropharyngeal cancers. HPV lesions represent a large group of sexually transmitted diseases. The objective of this study was to carry out a narrative review on the association between HPV lesions and genital and oral cavity carcinomas. We carried out a search in the electronic databases PubMed, Lilacs, Scielo, Medline and Google Scholar, using articles published between the years of 2017-2021, at the end, foram selected 36 articles. A large part of HPV infections are subclinical, or seem to, do not present significant symptoms and tend to disappear spontaneously. In this way, it is necessary to be aware of the two clinical and behavioral aspects of these injuries, enabling early diagnosis, avoiding evolution to more invasive stages, favoring effective treatment and better prognosis.

Los virus del papiloma humano (VPH) son miembros de la familia Papillomaviridae. El virus destaca por su tropismo por las células epiteliales, infectando exclusivamente mucosas epiteliales y cutáneas. El VPH-16 y el VPH-18 son subtipos clasificados como de alto riesgo, conocidos por su oncogenicidad, fuertemente asociados con cánceres anales, genitales y orofaríngeos. Las lesiones por VPH representan un gran grupo de enfermedades de transmisión sexual. El objetivo del presente estudio fue realizar una revisión narrativa sobre la asociación entre las lesiones por VPH y los carcinomas genitales y de cavidad oral. Realizamos una búsqueda en la base de datos electrónica PubMed, Lilacs, Scielo, Medline y Google Scholar, utilizando artículos publicados entre los años 2017-2021, al final se seleccionaron 36 artículos. La mayoría de las infecciones por VPH son subclínicas, es decir, no presentan síntomas importantes y tienden a desaparecer espontáneamente. Por lo tanto, es necesario tener conocimiento sobre los aspectos clínicos y conductuales de estas lesiones, que permitan un diagnóstico precoz, evitando la progresión a estadios más invasivos, favoreciendo un tratamiento eficaz y un mejor pronóstico.

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.

Human Papillomavirus 16 Lineage D is Associated with High Risk of Cervical Cancer in the Brazilian Northeast Region / Papillomavirus humano 16 da linhagem D associado a alto risco de câncer de colo do útero em região do nordeste brasileiro

Abstract Objective Similar to Human Papillomavirus (HPV) genotypes, different lineages of a genotype also have different carcinogenic capabilities. Studies have shown that specific genotype lineages of oncogenic HPV are associated with variable risks for the development of cervical intraepithelial neoplasia (CIN2/CIN3) and cervical cancer. The present study aimed to analyze the genetic diversity of the HPV16 genotype in women with CIN2/CIN3 and cervical cancer, from the northeast region of Brazil. Methods A cross-sectional multicenter study was conducted in the northeast region of Brazil, from 2014 to 2016. This study included 196 cases of HPV16 variants (59 and 137 cases of CIN2/CIN3 and cervical cancer, respectively). The difference of proportion test was used to compare patients with CIN2/CIN3 and cervical cancer, based on the prevalent HPV16 lineage (p < 0.05). Results According to the histopathological diagnosis, the percentage of lineage frequencies revealed a marginal difference in the prevalence of lineage A in CIN2/CIN3, compared with that in cervical cancer (p = 0.053). For lineage D, the proportion was higher in cancer cases (32.8%), than in CIN2/CIN3 cases (16.9%), with p = 0.023. Conclusion HPV16 lineage A was the most frequent lineage in both CIN2/CIN3 and cervical cancer samples, while lineage D was predominant in cervical cancer, suggesting a possible association between HPV16 lineage D and cervical cancer.

Resumo Objetivo Tanto os tipos quanto as linhagens do Papilomavírus Humano (HPV) parecem ter diferentes capacidades carcinogênicas e estão associados a riscos variados para o desenvolvimento de neoplasia intraepitelial cervical (NIC) e câncer de colo do útero. O presente estudo tem como objetivo analisar a diversidade genética do genótipo HPV 16 nos casos de NIC2/NIC3 e câncer de colo de útero em mulheres da região Nordeste do Brasil. Métodos Estudo transversal de base hospitalar realizado na região Nordeste do Brasil no período de 2014 a 2016. A amostra foi composta por 196 casos da variante HPV-16 (59 casos de NIC2/NIC3 e 137 de câncer do colo do útero). O teste de diferença de proporção foi usado para comparar os grupos NIC2/NIC3 e câncer de colo do útero por linhagem viral em relação à prevalência da linhagem HPV-16. Foi considerada significância estatística o valor de p < 0,05. Resultados As frequências de linhagem por diagnóstico histopatológico mostraram diferença limítrofe da linhagem A no grupo NIC2/NIC3 em relação ao grupo câncer de colo de útero (p = 0,053). Por outro lado, em relação à linhagem D, houve uma proporção maior nos casos de câncer (32,8%) quando comparado ao grupo NIC2/NIC3 (16,9%) e esta diferença se mostrou estatisticamente significante (p = 0,023). Conclusão A linhagem A do HPV-16 foi a mais frequente tanto nas amostras CIN2/CIN3 quanto nas amostras de câncer de colo de útero, enquanto a linhagem D predominou no câncer de colo do útero, sugerindo uma possível associação da linhagem D de HPV-16 com câncer de colo de útero.

Improved population coverage of the human papillomavirus vaccine after implementation of a school-based vaccination programme: the Singapore experience

INTRODUCTION@#Cervical cancer has a high disease burden in Singapore, and it is strongly associated with human papillomavirus (HPV) infections. Despite constant efforts to encourage vaccination, local HPV vaccine uptake remains low. Universal mass vaccination is a proven cost-effective method to reduce the cervical cancer disease burden. This paper reviews the newly implemented school-based HPV vaccination programme in Singapore and the factors that led to its success.@*METHODS@#Fully subsidised HPV vaccinations were offered to all Secondary 1 female students on an opt-in basis, starting as a rollout dose in 2019. One-time catchup vaccination was also offered to female students in Secondary 2-5. Eligible recipients were identified using enrolment data provided by Ministry of Education schools. A total of 19,144 students across 139 schools were offered the rollout dose, and 20,854 students across 140 schools were offered the catchup doses.@*RESULTS@#High vaccine uptake rates of 80.6%-87.3% were noted with the introduction of the school-based programme, translating to high vaccine coverage of 90.3%-93.4%. Only a small proportion of students (1.5%-1.9% per cohort) opted out. The rate of reported side effects, which were commonly known effects, was low at one in 1000. Among the students who reported side effects, those who received the second vaccine dose did so uneventfully.@*CONCLUSION@#High HPV vaccine coverage was achieved after implementation of the school-based immunisation programme. Timely assessment of knowledge lapses and targeted intervention, strong partnerships with stakeholders, constant on-site adaptation and positive social influence contributed to its success. This model can be applied to future school health programmes.

HPV vaccination in China based on website platform information / 上海预防医学

ObjectiveTo analyze the online public Q&A texts on HPV vaccine， focus on the important issues related to HPV vaccination and cervical cancer prevention in China， and propose strategies and suggestions. MethodsThe latent Dirichlet allocation （LDA） topic model was employed to extract key topics of 15 565 Q&A texts related to HPV vaccines from the social Q&A platform "Zhihu". The Baidu AI sentiment analysis tool was used to analyze the emotional tendencies of the texts corresponding to each topic， and the topics were classified based on the strategic coordinate method. ResultsOnline users focused on eight topics about HPV vaccine information. Among them， vaccination knowledge， HPV vaccination hesitation， and HPV vaccine development and marketing belonged to the low positivity-high negativity emotional topics， HPV infection and high-risk factors belonged to the low positivity-low negativity emotional topics， and HPV vaccine appointment channels， comparison between domestic and imported vaccines， HPV vaccines and cervical cancer prevention， and HPV vaccine types and selection were grouped under high positivity-low negativity emotional topics. ConclusionPublic concerns regarding HPV vaccines can be classified into three major dimensions： health knowledge， health beliefs， and health behaviors. Overall， the public's views and attitudes towards vaccine-related issues are not optimistic. Strengthening science publicity and education， enhancing vaccine supervision， and encouraging enterprises’ innovative research and development capability are effective strategies to improve public awareness of cervical cancer prevention and accelerate the full HPV vaccination coverage.

Eliminat Cervical Cancer, Focusing on Primary Prevention / 肿瘤防治研究

As one of the most severe malignant tumors, cervical cancer poses a significant threat to women. In 2020, the World Health Organization (WHO) introduced the "Global Strategy to Accelerate the Elimination of Cervical Cancer" in response to well-established tertiary prevention measures. Primary prevention measures prioritize health education and the administration of prophylactic human papillomavirus (HPV) vaccines. China currently offers five HPV vaccines supported by extensive research data specific to the Chinese population. This paper discusses the application of HPV vaccines in China and related issues that need to be paid attention to.

Factors Associated with Presence of Human Papillomavirus Infection among Women: Findings from New Cervical Cancer Screening in Kelantan, Malaysia

@#Introduction: Human papillomavirus (HPV) infection is known to cause cervical cancer worldwide. Recently, Malaysia introduced HPV DNA detection testing for cervical cancer screening program. However, knowledge regarding factors for HPV infection among women still limited. Thus, this study aimed to determine the prevalence and factors associated with HPV infection among women in Kelantan, a north-eastern state of Malaysia. Methods: This study used secondary data extracted from HPV DNA test registry book and HPV DNA laboratory request forms. Data on all Malaysian women aged 30 to 49 years old in 2019 reported in registry book were included. Simple random sampling was applied. All information from book and forms were collected using proforma and analysed using SPSS. The outcomes were categorised into HPV infection and non-HPV infection. The parameters related to factors associated with HPV infection were determined using multivariable logistic analysis. Results: The prevalence of HPV infection among women attending the new cervical screening was 8.4% (95% CI 6.4%, 10.3%). Those aged between 30 and 39 years old (AdjOR 2.09; 95% CI 1.16, 3.78, p=0.014), had 5 or more parities (AdjOR 2.82; 95% CI 1.58, 5.06, p<0.001) and hormonal contraception users (AdjOR 7.48; 95% CI 4.07, 13.76, p<0.001) were significantly associated with HPV infection. Conclusion: Overall, the prevalence of HPV infection from this study is comparable to the local and international studies. Age, number of parities and hormonal contraception users influence the HPV infection. This finding could help in designing more targeted screening for cervical cancer.

Safety of human papilloma virus vaccine based on Vaccine Adverse Event Reporting System from 2006 to 2021 / 中国生物制品学杂志

@#Objective To investigate the characteristics of distribution of adverse event(AE)associated with human papillomavirus(HPV)vaccine by analysis of data on AE collected from the Vaccine Adverse Event Reporting System(VAERS).Methods The data on AE reported in VAERS from January 1st,2006 to December 31st,2021 were analyzed and compared by using Pearson Chi-square test and Mann-Whitney U test.Results A total of 53 571 cases of AE were included in the study,in which the ratio of male to female was 0. 25∶1,and the median age of vaccinees was 15 years. A portion of 36. 1%of AE occurred after the first dose,while 90. 7% occurred within 3 d after vaccination. Both the gender ratios(χ~2=72. 570,P < 0. 001) and the median ages(Z = 4. 255,P < 0. 001)of vaccinees in non-serious and serious adverse event(SAE)showed significant difference. In terms of classification of SAE,hospitalization,prolonged hospitalization and disability were more common in females than in males,of which the percentages decreased with the increasing age. Among the AE,syncope was the most common clinical symptom. In the SAE,the highest proportion of deaths was caused by HPV2 vaccine,which was 19. 0%. The proportion of prolonged hospitalization caused by HPV4 vaccine was higher than that by HPV9vaccine. In general,HPV4 vaccine was more prone to cause SAE than HPV9 vaccine(χ~2=183. 267,P < 0. 001).Conclusion In all the AE,the largest proportion occurred in the age group of 9 ～ 17 years,followed by those in the groups of 18 ～ 26 and 27 ～ 45 years. Most of the AE occurred after the first dose. The clinical symptoms of AE caused by three vaccines were different. The analysis of distribution characteristics of AE may provide a reference for the study on clinical safety of HPV vaccine and optimization of vaccination.

Effects of recombinant human interferon α2a suppository on levels of inflammatory factors in cervical mucus of HPV-infected patients / 中国生物制品学杂志

@#Objective To investigate the effects of recombinant human interferon α2a(rhIFNα2a) suppository on the levels of inflammatory factors in the cervical mucus of patients infected with human papillomavirus(HPV).Methods A total of60 HPV-positive patients admitted to the Second Affiliated Hospital of Xi'an Jiaotong University from March to August in 2022 were selected as study objects,and then divided into observation and control groups,30 cases for each group,according to the random number table method.The observation group was given rhIFNα2a suppository therapy by vaginal medication,once every other day,continuous 10 times a month as a course of treatment,and 3 consecutive courses of treatment.The control group did not use drugs.The cervical secretions were collected and the levels of IL-1β,IL-2R,IL-6,IL-8,IL-10 and tumor necrosis factor-α(TNF-α) were measured by chemiluminescence assay.Results After 3 months of treatment,the levels inflammatory factors IL-1β,IL-6,IL-8 and TNF-α in cervical mucus of patients in the observation group were significantly lower than those in the control group(t=-2.717,-2.686,-3.178 and-3.25,respectively,each P <0.05).Compared with before treatment,the levels of IL-1β,IL-6,IL-8 and TNF-α in cervical mucus of patients in the observation group also decreased significantly(t=5.934,4.092,6.495 and 3.287,respectively,each P <0.01),while in the control group,only the level of IL-8 in cervical mucus was significantly different(t=2.345,P=0.024).Conclusion rhIFNα2a suppository can reduce the level of inflammatory factors in cervical mucus,attenuate the inflammatory response and accelerate the clearance of HPV.

Correlation between persistent high-risk human papillomavirus infection and vaginal microecology and cervical lesions / 中国热带医学

@#Abstract: Objective To investigate the correlation between persistent and non-persistent HPV infection and vaginal microecology and cervical lesions, and to provide the basis for HPV prevention and treatment. Methods In this prospective study, 229 female patients with high-risk type (HR-HPV) were selected for cervical cytology and vaginal microecological examination in the gynecological outpatient department of Baise Maternal and Child Health Hospital from January 2018 to June 2021. The patients were followed up for 1 year to detect persistent HR-HPV infection. The relationship between HR-HPV persistent infection and vaginal microecology and cervical lesions was analyzed using the HPV-negative group as a control. Results Among 229 patients with HR-HPV, there were 109 patients with persistent HR-HPV infection and 120 patients with non-persistent HR-HPV infection in 1-year follow-up, and the incidence of persistent HR-HPV infection was 47.6%. In the HR-HPV persistent and non-persistent infection and HPV-negative groups, the bacterial vaginal incidence was 20.2%, 15.0% and 8.6%, respectively; vulvovaginal candidiasis was 19.3%, 13.3% and 7.9%, respectively; trichomoniasis vaginitis was 12.8%, 9.2% and 4.5%, respectively; mixed infection was 10.1%, 6.7% and 2.7%; H2O2 detection rate was 24.8%, 18.3% and 12.0%,the positive rate of pH value was 52.3%, 40.8% and 36.4%, and microecological normal detection rate was 22.9%, 32.7% and 40.2%, respectively. There were significant differences among the three groups (χ2=10.634, 10.522, 9.010, 9.374, 10.054, 8.268, P<0.01). In the HR-HPV persistent and non-persistent infection groups, the rates of atypical squamous cell detection were 12.8% and 10.0%, and 8.3% and 4.2% for low-grade squamous cell lesions, and 4.6% and 1.7% for high-grade squamous cell carcinoma, 2.8% and 0 for squamous cell carcinoma, respectively. There was no significant difference in the composition of atypical squamous cells between the two groups (χ2=4.358, P>0.05), there were significant differences in the composition of low-grade, high-grade and squamous cell carcinoma (χ2=11.472, 12.685, 11.378, P<0.01). Spearman rank correlation analysis showed that the presence or extent of HPV infection was positively correlated with bacterial vaginosis, vulvovaginal candidiasis, trichomonal vaginitis and mixed infection (P<0.05), positively correlated with H2O2, sialdase, leucocyte esterase,pH positive and positive for all four items (P<0.05), negatively correlated with microecology (P<0.01), positively correlated with low grade, high grade and squamous cell carcinoma (P<0.01), and not significantly correlated with atypical squamous cell carcinoma (P>0.05). Conclusion Persistent cervical HPV infection is an important factor of dysregulation in vaginal microecology and aggravates the degree of dysregulation in vaginal microecology, which is related to the development of cervical lesions.