RESUMO
Cervical cancer (CC) is one of the best known malignancies. Currently, it is accepted that the etiological factor is persistent infection with high-risk human papillomavirus (HPV). Even before the identification of its etiological factors, methods such as Pap cytology and colposcopy were developed as tools for early diagnosis on CC and its precursor lesions. At the time when such tests were being developed, they were not fully accepted by the scientific community of the time; however, as time went by, the dissemination of knowledge, and more extensive application, these tests were finally included within the international guidelines. The implementation of programs with adequate coverage and quality allowed a significant reduction in the incidence and mortality of CC. However this did not occur widely, and CC is still a public health problem in developing countries. From the epidemiological and molecular viewpoint, knowledge on HPVs laid the foundations for the development of new prevention strategies based on vaccination and molecular detection of the causal agent, currently accepted as strategies for primary and secondary prevention. It is expected that the implementation of these strategies will have a greater impact on the control on CC and other malignancies associated with HPV infection.
El cáncer cervicouterino (CaCU) es una de las neoplasias mejor conocidas; actualmente es aceptado que el factor etiológico es la infección persistente por virus de papiloma humano (VPH) de alto riesgo. Sin embargo, aun antes de que se hubiera identificado el agente etiológico, se desarrollaron métodos, como la prueba citológica de Papanicolaou y la colposcopia, como herramientas para el diagnóstico temprano del CaCU y sus lesiones precursoras. En los inicios del desarrollo de ambas pruebas, estas no fueron del todo aceptadas por la comunidad científica de la época. Con el paso del tiempo, la divulgación del conocimiento y la aplicación más extensiva, se logró la aceptación y la inclusión de dichas pruebas en un gran número de guías a nivel internacional. La implementación de programas con cobertura adecuada y de calidad dio como resultado una reducción significativa en la incidencia y mortalidad por CaCU. Sin embargo, esto no se dio de manera generalizada y en países en vías de desarrollo es aún un problema de salud pública. El conocimiento sobre los VPH, desde el punto de vista epidemiológico y molecular, sentó las bases para el desarrollo de nuevas estrategias de prevención, basadas en la vacunación y en la detección molecular del agente causal, actualmente aceptadas como estrategias para prevención primaria y secundaria. Se espera que la aplicación de dichas estrategias tenga un impacto mayor en el control del CaCU y de otras neoplasias asociadas a la infección por VPH.
Assuntos
Detecção Precoce de Câncer/história , Infecções por Papillomavirus/história , Neoplasias do Colo do Útero/história , Colposcopia/história , Feminino , Saúde Global , História do Século XX , Humanos , Incidência , Teste de Papanicolaou/história , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/história , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/históriaRESUMO
Sylvilagus floridanus Papillomavirus (SfPV) causes growth of large horn-like tumors on rabbits. SfPV was described in cottontail rabbits (probably Sylvilagus floridanus) from Kansas and Iowa by Richard Shope in 1933, and detected in S. audubonii in 2011. It is known almost exclusively from the US Midwest. We explored the University of Kansas Natural History Museum for historical museum specimens infected with SfPV, using molecular techniques, to assess if additional wild species host SfPV, and whether SfPV occurs throughout the host range, or just in the Midwest. Secondary aims were to detect distinct strains, and evidence for strain spatio-temporal specificity. We found 20 of 1395 rabbits in the KU collection SfPV symptomatic. Three of 17 lagomorph species (S. nuttallii, and the two known hosts) were symptomatic, while Brachylagus, Lepus and eight additional Sylvilagus species were not. 13 symptomatic individuals were positive by molecular testing, including the first S. nuttallii detection. Prevalence of symptomatic individuals was significantly higher in Sylvilagus (1.8%) than Lepus. Half of these specimens came from Kansas, though new molecular detections were obtained from Jalisco-Mexico's first-and Nebraska, Nevada, New Mexico, and Texas, USA. We document the oldest lab-confirmed case (Kansas, 1915), pre-dating Shope's first case. SfPV amplification was possible from 63.2% of symptomatic museum specimens. Using multiple methodologies, rolling circle amplification and, multiple isothermal displacement amplification in addition to PCR, greatly improved detection rates. Short sequences were obtained from six individuals for two genes. L1 gene sequences were identical to all previously detected sequences; E7 gene sequences, were more variable, yielding five distinct SfPV1 strains that differing by less than 2% from strains circulating in the Midwest and Mexico, between 1915 and 2005. Our results do not clarify whether strains are host species specific, though they are consistent with SfPV specificity to genus Sylvilagus.
Assuntos
Papillomavirus de Coelho Cottontail/isolamento & purificação , Infecções por Papillomavirus/veterinária , Coelhos/virologia , Neoplasias Cutâneas/veterinária , Animais , Antígenos Virais/genética , Sequência de Bases , Colorado/epidemiologia , Papillomavirus de Coelho Cottontail/genética , Papillomavirus de Coelho Cottontail/patogenicidade , DNA Viral/genética , DNA Viral/isolamento & purificação , Genes Virais , História do Século XX , História do Século XXI , Especificidade de Hospedeiro , Kansas/epidemiologia , México/epidemiologia , Meio-Oeste dos Estados Unidos/epidemiologia , Dados de Sequência Molecular , Museus , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/história , Infecções por Papillomavirus/virologia , Filogenia , Coelhos/classificação , Homologia de Sequência do Ácido Nucleico , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/história , Neoplasias Cutâneas/virologia , Especificidade da Espécie , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/história , Infecções Tumorais por Vírus/veterinária , Infecções Tumorais por Vírus/virologia , Proteínas Estruturais Virais/genéticaRESUMO
The history on the relationship of VPH infection and cervical cancer was examined. Findings were initially reported in Maracaibo(1971), later in Mexico(1973) and thereafter several studies on the ultrastructure and immunohistochemistry of VPH infection and its role on cervical cancer were described. The ultrastructural findings of viral particles of HPV and their proteins, as well as their role in the incorporation of the viral genome to the human cervical cells were also described. Glycoproteins on the surface of cervical cells were reviewed and their importance on HPV infection was related to p16, blood group antigens and early genetic changes in the cell cycle with loss of heterozigocity, all of which, stimulated by the high risk HPV infection lead to cervical cancer.