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1.
Cancer Epidemiol Biomarkers Prev ; 30(2): 245-247, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33547144

RESUMO

Self-sampling is poised to be a disruptor for cervical screening. So far, cancer screening has been a causality of COVID-19; however, the opposite may transpire for self-sampling. Self-sampling enables socially distanced cervical screening with an outreach that extends to underserved populations. As evidence mounts that self-sampling is noninferior to clinician-taken samples, the focus for self-sampling is now as a primary screening option for all women. Now, we have evidence from a modeling study (using Australia as an exemplar) to suggest that program effectiveness with primary self-sampling would be better than the current program, even if sensitivity is lower. Regulatory issues, suitable triage strategies, and clear communication about self-sampling are hurdles yet to be overcome. Nevertheless, existing evidence coupled with COVID-19 could be the tipping point for wider introduction of self-sampling.See related article by Smith et al., p. 268.


Assuntos
Papillomaviridae , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Austrália , Detecção Precoce de Câncer , Feminino , Humanos , Programas de Rastreamento , Infecções por Papillomavirus/diagnóstico , Manejo de Espécimes , Neoplasias do Colo do Útero/diagnóstico
2.
Ther Umsch ; 78(2): 93-98, 2021.
Artigo em Alemão | MEDLINE | ID: mdl-33615865

RESUMO

Importance of the Pap smear in the age of HPV testing Abstract. Screening for cervical cancer prevention is considered a success story. Since the introduction of the Pap test in the 1950s, the incidence and mortality of cervical carcinomas has decreased dramatically in the industrialized world. In developing countries, and especially in certain countries in Africa, cervical cancer is still one of the most common fatal cancers due to the lack of screening and therapeutic options. For decades, Pap tests and colposcopy were the basis of cervical cancer screening. In the early 1980s, it became known that almost without exception cervical carcinomas require infection with certain human papilloma viruses (HPV). Among other things, this finding also revolutionized cervical cancer screening. The quality of the Pap test is influenced by the conditions of collection and by the so-called interobserver variability. Overall, cytology shows a good specificity of 95 % with a lower sensitivity of 70 %. Additional immunohistochemical tests to determine the biomarkers p16 and Ki-67 can increase the sensitivity of the Pap test up to 94 % (analogous to the HPV test), which is why cytological tests are still considered very effective in countries with sufficient resources and expertise. In contrast, the HPV test is not subjective and has a high sensitivity of 94 %. However, the specificity is worse than for the Pap test, which is why HPV-based screening carries an increased risk of unnecessary clarification and therapy. The superiority of HPV versus cytological screening seems to be proven under defined study conditions, but only after the second or third screening round. If screening is performed opportunistically, as in Switzerland, there is a risk of so-called lost follow-up. It is precisely the failure to take advantage of screening examinations or their performance at irregular intervals that is considered the most significant risk factor for the development of cervical carcinoma. It should also be remembered that the HPV test only reflects the current viral shedding but does not provide any information about the time and duration of HPV infection. Further studies are necessary to determine long-term results and cost-effectiveness.


Assuntos
Papillomaviridae , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Detecção Precoce de Câncer , Feminino , Humanos , Programas de Rastreamento , Teste de Papanicolaou , Infecções por Papillomavirus/diagnóstico , Gravidez , Suíça , Neoplasias do Colo do Útero/diagnóstico
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(1): 98-103, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33474897

RESUMO

Objective: R6G-ddATP was used as a dideoxy fluorescence substrate to establish the single base end extension (SNaPShot)-gel fluorescence method for the rapid detection of the genotypes of three high-risk human papillomaviruses (HR-HPV) ( HPV18, HPV33 and HPV35) genotypes. Methods: HPV quality control products were used as as samples, and R6G-ddATP dideoxy fluorescence reagent was used as substrate. Firstly, HPV was amplified by using universal primers to obtain the first round of amplified products, which were purified and used as templates for subsequent SNaPShot reactions. Then, specific one-step extension primers were used to perform SNaPShot reaction to generate R6G-fluorescence-labeled DNA extension products. The product was subjected to agarose gel electrophoresis, the results of which were observed under a Gel Imager, and the HPV genotyping was done with different one-step extension primers. Each sample was tested three times and the results were compared with DNA sequencing results. Results: The preferred annealing temperature for SNaPShot reaction is 55 ℃. Three HPV genotypes were examined by R6G-ddATP/SNaPShot gel fluorescence assay under optimal conditions, and the results were consistent with DNA sequencing results. Conclusion: The R6G-ddATP/SNaPShot-gel fluorescence method for the micro-detection methods of three HR-HPV genotypes was successfully established and can be used for rapid detection of HPV genotypes.


Assuntos
Alphapapillomavirus , Papillomaviridae , Infecções por Papillomavirus , DNA Viral/genética , Nucleotídeos de Desoxiadenina , Didesoxinucleotídeos , Genótipo , Humanos , Papillomaviridae/genética , Reação em Cadeia da Polimerase
6.
Anticancer Res ; 41(1): 163-167, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419809

RESUMO

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) demonstrates aggressive biological behavior in subgroups of patients with specific molecular characteristics. Concerning metastatic potential, disruption of cell to cell adhesion is a critical event in epithelial malignancies including OSCC. Our aim was to investigate the role of E-Cadherin expression in OSCC patients as a valuable protein marker. MATERIALS AND METHODS: Fifty (n=50) tissue sections derived from primary OSCCs were analyzed by implementing an immunohistochemistry (IHC) assay based on a proper anti-E-cadherin antibody. Digital image analysis was also implemented for an objective evaluation of the corresponding protein expression levels. RESULTS: E-cadherin altered expression (low to negative) was observed in 34/50 (68%) cases, whereas the rest (16/50-32%) demonstrated normal (high to moderate) expression. E-Cadherin abnormal expressionwas associated with the stage of the examined malignancies (p=0.023), whereas no significant correlations with grade, gender, smoking status or human papilloma virus (HPV) history were observed. CONCLUSION: E-Cadherin down regulation is frequently observed in OSCC and is correlated to a progressively aggressive phenotype of the malignancy in the corresponding patients (advanced stage), but it seems that the impact of HPV persistent infection on these patients is not a critical parameter.


Assuntos
Alphapapillomavirus , Caderinas/genética , Carcinoma de Células Escamosas/etiologia , Expressão Gênica , Neoplasias Bucais/etiologia , Infecções por Papillomavirus/complicações , Biomarcadores Tumorais , Caderinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Suscetibilidade a Doenças , Feminino , Humanos , Imuno-Histoquímica , Masculino , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Gradação de Tumores , Estadiamento de Neoplasias , Infecções por Papillomavirus/virologia
7.
Anticancer Res ; 41(1): 269-277, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419821

RESUMO

AIM: To investigate the level of agreement between three non-invasive methods for hrHPV diagnosis in oral and oropharyngeal squamous cell carcinoma (OSCC, OPSCC) and in oral mucosal lesions. MATERIALS AND METHODS: For hrHPV DNA FTA Elute card™ and Anyplex II HPV28™ were used and for hrHPV mRNA PreTect SEE™ in tumour patients (n=60), non-tumour lesions (n=51), immunosuppression or previous hrHPV-infection (n=32). RESULTS: The level of agreement between the DNA-methods was 82.2% (k=0.54, p=0.001). Pair-wise comparison for the FTA Elute card were close to the reference (AUC=0.83, 95% CI=0.73-0.90). hrHPV mRNA was diagnosed in 50% of the tumours, with an agreement level of 58.3%, compared to Anyplex II (k=0.17, p=0.04). The hrHPV positivity in oral lesions was 3.9% for immunosuppression and for previous HPV infection 9.4%. CONCLUSION: The FTA card is reliable for hrHPV DNA diagnosis while mRNA gives an insight into viral activity and correlates with severity of the lesion.


Assuntos
Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Estomatite/diagnóstico , Estomatite/virologia , Adulto , Idoso , Biópsia , DNA Viral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Infecções por Papillomavirus/complicações , Reação em Cadeia da Polimerase , Prevalência , Curva ROC , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Estomatite/complicações , Suécia/epidemiologia
8.
BMJ ; 372: m4931, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514507

RESUMO

OBJECTIVE: To evaluate the association between human papillomavirus (HPV) vaccination and serious adverse events in adolescent girls in South Korea. DESIGN: Cohort study. SETTING: A large linked database created by linking the Korea Immunization Registry Information System and the National Health Information Database, between January 2017 and December 2019. PARTICIPANTS: 441 399 girls aged 11-14 years who had been vaccinated in 2017: 382 020 had been vaccinated against HPV and 59 379 had not been vaccinated against HPV. MAIN OUTCOME MEASURES: Outcomes were 33 serious adverse events, including endocrine, gastrointestinal, cardiovascular, musculoskeletal, haematological, dermatological, and neurological diseases. A cohort design was used for the primary analysis and a self-controlled risk interval design for the secondary analysis; both analyses used a risk period of one year after HPV vaccination for each outcome. Incidence rate and adjusted rate ratios were estimated using Poisson regression in the primary analysis, comparing the HPV vaccinated group with the HPV unvaccinated group, and adjusted relative risks were estimated using conditional logistic regression in the secondary analysis. RESULTS: Among the 33 predefined serious adverse events, no associations were found with HPV vaccination in the cohort analysis, including Hashimoto's thyroiditis (incidence rate per 100 000 person years: 52.7 v 36.3 for the vaccinated and unvaccinated groups; adjusted rate ratio 1.24, 95% confidence interval 0.78 to 1.94) and rheumatoid arthritis (incidence rate per 100 000 person years: 168.1 v 145.4 for the vaccinated and unvaccinated groups; 0.99, 0.79 to 1.25), with the exception of an increased risk observed for migraine (incidence rate per 100 000 person years: 1235.0 v 920.9 for the vaccinated and unvaccinated groups; 1.11, 1.02 to 1.22). Secondary analysis using self-controlled risk intervals confirmed no associations between HPV vaccination and serious adverse events, including migraine (adjusted relative risk 0.67, 95% confidence interval 0.58 to 0.78). Results were robust to varying follow-up periods and for vaccine subtypes. CONCLUSIONS: In this nationwide cohort study, with more than 500 000 doses of HPV vaccines, no evidence was found to support an association between HPV vaccination and serious adverse events using both cohort analysis and self-controlled risk interval analysis. Inconsistent findings for migraine should be interpreted with caution considering its pathophysiology and the population of interest.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Vacinas contra Papillomavirus/efeitos adversos , Adolescente , Criança , Estudos de Coortes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Feminino , Humanos , Infecções por Papillomavirus/prevenção & controle , Sistema de Registros , República da Coreia/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle
9.
BMC Infect Dis ; 21(1): 11, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407188

RESUMO

BACKGROUND: Combined with cancer screening programs, vaccination against human papillomavirus (HPV) can significantly reduce the high health and economic burden of HPV-related disease in Japan. The objective of this study was to assess the health impact and cost effectiveness of routine and catch-up vaccination of girls and women aged 11-26 years with a 4-valent (4vHPV) or 9-valent HPV (9vHPV) vaccine in Japan compared with no vaccination. METHODS: We used a mathematical model adapted to the population and healthcare settings in Japan. We compared no vaccination and routine vaccination of 12-16-year old girls with 1) 4vHPV vaccine, 2) 9vHPV vaccine, and 3) 9vHPV vaccine in addition to a temporary catch-up vaccination of 17-26 years old girls and women with 9vHPV. We estimated the expected number of disease cases and deaths, discounted (at 2% per year) future costs (in 2020 ¥) and discounted quality-adjusted life years (QALY), and incremental cost effectiveness ratios (ICER) of each strategy over a time horizon of 100 years. To test the robustness of the conclusions, we conducted scenario and sensitivity analyses. RESULTS: Over 100 years, compared with no vaccination, 9vHPV vaccination was projected to reduce the incidence of 9vHPV-related cervical cancer by 86% (from 15.24 new cases per 100,000 women in 2021 to 2.02 in 2121). A greater number of cervical cancer cases (484,248) and cancer-related deaths (50,102) were avoided through the described catch-up vaccination program. Routine HPV vaccination with 4vHPV or 9vHPV vaccine prevented 5,521,000 cases of anogenital warts among women and men. Around 23,520 and 21,400 diagnosed non-cervical cancers are prevented by catch-up vaccination among women and men, respectively. Compared with no vaccination, the ICER of 4vHPV vaccination was ¥975,364/QALY. Compared to 4vHPV, 9vHPV + Catch-up had an ICER of ¥1,534,493/QALY. CONCLUSIONS: A vaccination program with a 9-valent vaccine targeting 12 to 16 year-old girls together with a temporary catchup program will avert significant numbers of cases of HPV-related diseases among both men and women. Furthermore, such a program was the most cost effective among the vaccination strategies we considered, with an ICER well below a threshold of ¥5000,000/QALY.


Assuntos
Alphapapillomavirus/imunologia , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Programas de Imunização/economia , Infecções por Papillomavirus/prevenção & controle , Saúde Pública , Neoplasias do Colo do Útero/prevenção & controle , Vacinação/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise Custo-Benefício , Feminino , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Humanos , Incidência , Lactente , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/transmissão , Infecções por Papillomavirus/virologia , Anos de Vida Ajustados por Qualidade de Vida , Neoplasias do Colo do Útero/virologia , Vacinação/métodos , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-33503149

RESUMO

Sexually transmitted infections (STIs) represent a global health problem with variable prevalence depending on the geographical region and the type of population. Human papillomavirus (HPV) encompasses widespread virus types related to cervical carcinogenesis. The present study investigated the molecular prevalence of HPV and seven other important STIs in asymptomatic women working or studying at a Brazilian university. A secondary aim was to assess cytological abnormalities associated with HPV and other STIs coinfections. We recruited 210 women from a Brazilian university. HPV was detected using a single-round polymerase chain reaction (sPCR) followed by a viral genotyping by restriction fragment length polymorphism (RFLP-PCR). The presence of seven STIs: Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Trichomonas vaginalis, Mycoplasma genitalium, herpes simplex virus (HSV)-1 and HSV-2 was detected by multiplex PCR (M-PCR). Furthermore, cytological findings and epidemiological characteristics were evaluated.The mean age of the participants was 27.1 years old. HPV prevalence was 33.8%, and HPV16 was the most frequently detected papillomavirus genotype. Moreover, multiple HPV infections were common (42.2%). We detected at least one STI agent in 11.4% of the tested women, most frequently C. trachomatis (6.7%). Among HPV-positive women, 14.1% were coinfected with other STI agents. Cytological abnormalities were observed in 9.5% of smears, and HPV-DNA, high-risk HPV (HR-HPV), HPV16 and HPV multiple infections were associated with abnormal cytological findings. There was a high prevalence of HPV, and C. trachomatis was the most prevalent STI agent, with low rates of cytological abnormalities. These findings highlight the need of timely STI diagnosis in young asymptomatic women and of a public policy design for STI prevention.


Assuntos
Portador Sadio/epidemiologia , Papillomaviridae , Infecções por Papillomavirus/epidemiologia , Doenças Sexualmente Transmissíveis/epidemiologia , Adulto , Alphapapillomavirus , Brasil/epidemiologia , Feminino , Genes Virais , Genótipo , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prevalência , Universidades
11.
Arch Virol ; 166(3): 853-862, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33486629

RESUMO

The aim of this study was to describe the distribution of human papillomavirus (HPV) genotypes among cervical cancers and pre-cancers in Shaanxi province of western China. A total of 17,341 women who were screened for cervical cancer from January 2014 to December 2016, using HPV genotyping and ThinPrep cytologic test were included. The prevalence and attribution of HPV genotypes were stratified by cervical lesion and age group. Of the subjects, 26.3% were infected with HPV, 28.0% of whom had multiple infections. The crude HPV prevalence increased from atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions (ASCUS/LSIL, 64.3%) to high-grade squamous intraepithelial lesions (HSIL, 79.8%) and to invasive cervical cancer (ICC, 89.7%, P < 0.001). The three most prevalent genotypes were HPV 16 (8.0%), 58 (4.2%), and 52 (4.0%), and HPV 16, 31 and 33 were positively correlated with increased severity of cervical lesions. Additionally, the divalent vaccine genotypes HPV 16 and 18 accounted for 68.2% of ICC cases. Although 78.5% of ICC and 60.3% of HSIL cases were attributed to 9-valent vaccine genotypes, the other genotypes not covered by any vaccine still resulted in increases in coverage, with 1.5% for ICC, 5.3% for HSIL, and 13.5% for ASCUS/LSIL. HPV prevalence in western China was consistent with other regions of China. Early vaccination with 9-valent HPV vaccine is recommended in this locality for females younger than 26 years with no prior infection, while divalent the vaccine is more appropriate for women between 26 and 45 years, considering the efficacy, safety and cost-effectiveness of vaccines.


Assuntos
Neoplasia Intraepitelial Cervical/epidemiologia , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Papillomavirus Humano 31/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Neoplasia Intraepitelial Cervical/virologia , China/epidemiologia , Feminino , Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Papillomavirus Humano 31/genética , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/uso terapêutico , Prevalência , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação
12.
Hautarzt ; 72(2): 106-113, 2021 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-33337514

RESUMO

Human papillomavirus (HPV) infections belong to the most frequent viral infections. Besides benign common warts and benign and malignant lesions of the head and neck area, HPV can induce anogenital dysplasias and cancers. Since the year 2007, effective and safe prophylactic HPV vaccines are licensed in Europe. To date, a bivalent (HPV16 and 18) and a nonavalent HPV vaccine (HPV6, 11, 16, 18, 31, 33, 45, 52, and 58) are commercially available in Germany. The German standing committee on vaccination (STIKO) currently recommends gender-neutral prophylactic HPV-vaccination between 9 and 14 years of age, with the possibility of catch-up vaccination until the age of 17 years. Besides a large proportion of HPV-induced anogenital dysplasias and carcinomas, the nonavalent HPV vaccine also prevents anogenital warts. Iatrogenically immunocompromised patients older than 17 years of age should also receive prophylactic HPV vaccination, preferrably by the age of 26 years. In case of already acquired HPV infection or existing HPV-induced lesions prophylactic vaccination does not lead to accelerated HPV elimination or clearance of lesions.


Assuntos
Condiloma Acuminado , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Adulto , Europa (Continente) , Alemanha , Humanos , Infecções por Papillomavirus/prevenção & controle , Vacinação
13.
An Bras Dermatol ; 96(1): 1-16, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33341319

RESUMO

Infection with human papilloma virus (HPV) is related to a great number of cutaneous and mucosal manifestations. The spectrum of HPV ranges from inapparent infections, through various clinical benign presentations including cutaneous and mucosal disease, to malignant and premalignant conditions. New HPV types are currently described in the literature; many of them are characterized as high-risk types due to their oncogenic potential. Knowledge regarding their epidemiology and pathogenesis is important to understand not only infection and disease processes, but also to formulate the clinical and laboratory basis for diagnosis, therapeutics, and prophylactic measures. This non-systematic review aims to discuss and to update those aspects, with an emphasis on relevant topics for dermatologists. HPV infection and related diseases in the Brazilian scenario are highlighted, including common dermatologic conditions seen at clinics as well as the condition of a public health problem as a sexually transmitted infection. The oncogenicity of the virus and the variety of clinical outcomes - especially in the immunocompromised individuals - are addressed.


Assuntos
Alphapapillomavirus , Papillomaviridae , Infecções por Papillomavirus , Lesões Pré-Cancerosas , Brasil/epidemiologia , Humanos , Infecções por Papillomavirus/epidemiologia
15.
Recent Results Cancer Res ; 217: 141-155, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33200365

RESUMO

Human papillomaviruses (HPVs) are small DNA viruses that infect basal epithelial cells and are the causative agents of cervical, anogenital, as well as oral cancers. High-risk HPVs are responsible for nearly half of all virally induced cancers. Viral replication and amplification are intimately linked to the stratified epithelium differentiation program. The E6 and E7 proteins contribute to the development of cancers in HPV positive individuals by hijacking cellular processes and causing genetic instability. This genetic instability induces a robust DNA damage response and activating both ATM and ATR repair pathways. These pathways are critical for the productive replication of high-risk HPVs, and understanding how they contribute to the viral life cycle can provide important insights into HPV's role in oncogenesis. This review will discuss the role that differentiation and the DNA damage responses play in productive replication of high-risk HPVs as well as in the development of cancer.


Assuntos
Alphapapillomavirus , Reparo do DNA , Proteínas Oncogênicas Virais , Papillomaviridae , Infecções por Papillomavirus , Humanos , Proteínas Oncogênicas Virais/genética , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Replicação Viral
16.
Recent Results Cancer Res ; 217: 157-195, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33200366

RESUMO

Human papillomavirus (HPV) is the most common sexually transmitted infection, currently affecting close to 80 million Americans. Importantly, HPV infection is recognized as the etiologic factor for numerous cancers, including cervical, vulval, vaginal, penile, anal, and a subset of oropharyngeal cancers. The prevalence of HPV infection and its associated diseases are a significant problem, affecting millions of individuals worldwide. Likewise, the incidence of HPV infection poses a significant burden on individuals and the broader healthcare system. Between 2011 and 2015, there were an estimated 42,700 new cases of HPV-associated cancers each year in the United States alone. Similarly, the global burden of HPV is high, with around 630,000 new cases of HPV-associated cancer occurring each year. In the last decade, a total of three preventive major capsid protein (L1) virus-like particle-based HPV vaccines have been licensed and brought to market as a means to prevent the spread of HPV infection. These prophylactic vaccines have been demonstrated to be safe and efficacious in preventing HPV infection. The most recent iteration of the preventive HPV vaccine, a nanovalent, L1-VLP vaccine, protects against a total of nine HPV types (seven high-risk and two low-risk HPV types), including the high-risk types HPV16 and HPV18, which are responsible for causing the majority of HPV-associated cancers. Although current prophylactic HPV vaccines have demonstrated huge success in preventing infection, existing barriers to vaccine acquisition have limited their widespread use, especially in low- and middle-income countries, where the burden of HPV-associated diseases is highest. Prophylactic vaccines are unable to provide protection to individuals with existing HPV infections or HPV-associated diseases. Instead, therapeutic HPV vaccines capable of generating T cell-mediated immunity against HPV infection and associated diseases are needed to ameliorate the burden of disease in individuals with existing HPV infection. To generate a cell-mediated immune response against HPV, most therapeutic vaccines target HPV oncoproteins E6 and E7. Several types of therapeutic HPV vaccine candidates have been developed including live-vector, protein, peptide, dendritic cell, and DNA-based vaccines. This chapter will review the commercially available prophylactic HPV vaccines and discuss the recent progress in the development of therapeutic HPV vaccines.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Infecções por Papillomavirus/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação
17.
Int J Cancer ; 148(2): 277-284, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-32638362

RESUMO

The age-standardised incidence of cervical cancer in Europe varies widely by country (between 3 and 25/100000 women-years) in 2018. Human papillomavirus (HPV) vaccine coverage is low in countries with the highest incidence and screening performance is heterogeneous among European countries. A broad group of delegates of scientific professional societies and cancer organisations endorse the principles of the WHO call to eliminate cervical cancer as a public health problem, also in Europe. All European nations should, by 2030, reach at least 90% HPV vaccine coverage among girls by the age of 15 years and also boys, if cost-effective; they should introduce organised population-based HPV-based screening and achieve 70% of screening coverage in the target age group, providing also HPV testing on self-samples for nonscreened or underscreened women; and to manage 90% of screen-positive women. To guide member states, a group of scientific professional societies and cancer organisations engage to assist in the rollout of a series of concerted evidence-based actions. European health authorities are requested to mandate a group of experts to develop the third edition of European Guidelines for Quality Assurance of Cervical Cancer prevention based on integrated HPV vaccination and screening and to monitor the progress towards the elimination goal. The occurrence of the COVID-19 pandemic, having interrupted prevention activities temporarily, should not deviate stakeholders from this ambition. In the immediate postepidemic phase, health professionals should focus on high-risk women and adhere to cost-effective policies including self-sampling.


Assuntos
Alphapapillomavirus/imunologia , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Saúde Pública/métodos , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Alphapapillomavirus/fisiologia , /prevenção & controle , Detecção Precoce de Câncer , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Saúde Pública/normas , Saúde Pública/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/imunologia , Vacinação/métodos , Organização Mundial da Saúde , Adulto Jovem
18.
Adv Exp Med Biol ; 1287: 105-122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33034029

RESUMO

The NOTCH pathway is critical for the development of many cell types including the squamous epithelium lining of cutaneous and mucosal surfaces. In genetically engineered mouse models, Notch1 acts as one of the first steps to commit basal keratinocytes to terminally differentiate. Similarly, in human head and neck squamous cell cancers (HNSCCs), NOTCH1 is often lost consistent with its essential tumor-suppressive role for initiating keratinocyte differentiation. However, constitutive NOTCH1 activity in the epithelium results in expansion of the spinous keratinocyte layers and impaired terminal differentiation is consistent with the role of NOTCH1 as an oncogene in other cancers, especially in T-cell acute lymphoblastic leukemia. We have previously observed that NOTCH1 plays a dual role as both a tumor suppressor and oncogene, depending on the mutational context of the tumor. Namely, gain or loss or NOTCH1 activity promotes the development of human papillomavirus (HPV)-associated cancers. The additional HPV oncogenes likely disrupt the tumor-suppressive activities of NOTCH and enable the oncogenic pathways activated by NOTCH to promote tumor growth. In this review, we detail the role of NOTCH pathway in head and neck cancers with a focus on HPV-associated cancers.


Assuntos
Carcinogênese , Neoplasias Bucais/metabolismo , Neoplasias Bucais/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virologia , Humanos , Infecções por Papillomavirus/virologia
19.
Sports Health ; 13(1): 91-94, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32662740

RESUMO

BACKGROUND: The preparticipation physical evaluation (PPE) is a requirement for high school sport participation in most states, but its location and role in preventive health care for adolescents is often questioned. HYPOTHESIS: Athletes who had their PPE performed in an office setting, in particular) by their primary care physician (PCP), will have higher human papillomavirus (HPV) immunization rates than those who had their PPE done in a group setting at a mass-participation PPE. STUDY DESIGN: Retrospective cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: The PPE forms and immunization records for athletes at a single high school were reviewed to determine the location of PPE, the signing practitioner, and HPV immunization status. RESULTS: A total of 488 athletes (286 males, 202 females) were included; 51% had received at least 1 dose of the HPV vaccine while 39% had completed the series. There was no significant difference in vaccination rates between examination in an office setting versus a group setting. Athletes receiving their PPE at an urgent care facility had significantly lower rates of HPV series completion than all other settings (29% vs 43%; P = 0.004). PPE completion by the athlete's PCP was associated with higher rates of vaccine series completion (46% vs 34%; P = 0.014). CONCLUSION: Athletes who completed their PPE in mass event and office-based settings had similar rates of HPV vaccine series initiation and completion. PPEs done at urgent care facilities were associated with low rates of vaccine series completion, while those done by a PCP were associated with higher rates. CLINICAL RELEVANCE: HPV immunization rates in athletes are low, and the PPE represents a potential opportunity to improve immunization rates.


Assuntos
Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Exame Físico , Atenção Primária à Saúde/estatística & dados numéricos , Esportes , Vacinação/estatística & dados numéricos , Adolescente , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Utilização de Instalações e Serviços , Feminino , Humanos , Masculino , Michigan , Estudos Retrospectivos , Instituições Acadêmicas
20.
Am J Surg Pathol ; 45(1): 108-118, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32868526

RESUMO

Sinonasal squamous cell carcinoma (SNSCC) is sometimes associated with high-risk human papillomavirus (HR-HPV) infection and inverted sinonasal papilloma or oncocytic sinonasal papilloma. Frequent mutations of EGFR and KRAS are reported in inverted sinonasal papilloma-related sinonasal squamous cell carcinoma (ISP-SCC) and oncocytic sinonasal papilloma-related SNSCC, respectively. Here, we attempted to determine the prevalence and the prognostic significances of these alterations in SNSCC. We retrospectively collected 146 SNSCCs, including 14 ISP-SCCs, and comprehensively analyzed the HR-HPV infection by human papillomavirus (HPV)-RNA in situ hybridization, EGFR gene copy number gain (CNG) by chromogenic in situ hybridization, and gene mutations in EGFR and KRAS by Sanger sequencing. HR-HPV was detected in 11 cases (7.5%), whereas all 14 ISP-SCCs were negative. EGFR mutations were present in 21 (14.7%) of 143 SNSCCs, including 13/14 (92.9%) ISP-SCCs and 8/129 (6.2%) non-ISP-SCCs (P<0.0001). The majority of EGFR mutations were exon 20 insertions, with the remainder composed of deletions and single-nucleotide substitutions in exons 19 and 20. All of 142 SNSCCs harbored no KRAS mutation. EGFR CNG was detected in 41 (28.1%) of 146 SNSCCs; all of them were HPV negative and 3 had EGFR mutations. Collectively, EGFR mutation, EGFR CNG, and HR-HPV were essentially mutually exclusive, and each subgroup had distinct clinicopathologic features. The HPV-negative/EGFR-mutant group, the HPV-negative/EGFR CNG-positive group, and the triple-negative group had significantly worse prognoses than the HPV-positive group (P=0.0265, 0.0264, and 0.0394, respectively). In conclusion, EGFR mutation may play a pathogenetically important role in some populations of SNSCCs, especially ISP-SCCs. The molecular subclassification of SNSCCs may contribute to prognostic prediction and molecular-targeted precision medicine.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/virologia , Infecções por Papillomavirus/complicações , Neoplasias dos Seios Paranasais/genética , Neoplasias dos Seios Paranasais/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Variações do Número de Cópias de DNA , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos
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