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Publication
Patogénese da infeção por vírus do papiloma humano (HPV)
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Abstract(s)
O vírus do papiloma humano (HPV) é responsável por cerca de 99% dos casos de cancro do colo do útero e em Portugal é o 3º mais frequente em mulheres mais jovens. Neste contexto, o HPV tipo 16 e o HPV tipo 18 são os que mais fortemente estão associados ao cancro do colo do útero.
A infeção começa nas células indiferenciadas do epitélio na camada basal, e à medida que estas vão proliferando, o vírus assegura a amplificação genómica e manutenção da replicação bem como o estabelecimento da infeção nas células mais superficiais do epitélio. Como consequência da infeção, podem desenvolver-se manifestações clínicas benignas, como verrugas a nível da pele, verrugas anogenitais ou manifestações malignas, como o cancro do colo do útero, entre outros.
Na maior parte das vezes, o sistema imunitário consegue assegurar a regressão da infeção. Porém, em alguns casos, particularmente nas infeções por HPVs de alto risco, e com a intervenção direta das proteínas virais E5, E6 e E7, o vírus consegue garantir a fuga ao sistema imunitário, auxiliado ainda pelo facto de a infeção ser intraepitelial e desta forma não se desencadear virémia nem resposta inflamatória.
A evasão ao sistema imunitário, aliada à desregulação das proteínas E6 e E7 virais, (que é consequência do fenómeno de integração do material genético viral no genoma do hospedeiro), tem repercussões a nível do ciclo celular normal, o que gera uma instabilidade que pode estar na origem do desenvolvimento de cancro do colo do útero.
O diagnóstico passa pela realização da citologia, que revela uma grande especificidade, e também por testes de diagnóstico molecular de HPV que apresentam a vantagem de uma sensibilidade aumentada comparativamente ao método anterior. No que diz respeito à prevenção e tratamento, a vacina atualmente comercializada em Portugal é a Gardasil® 9 que apresenta valores muito promissores de eficácia na prevenção. Por sua vez, o tratamento é aplicado consoante as manifestações clínicas que o doente apresente, ou consoante o estadio de cancro do colo do útero em que este se encontre.
Human papillomavirus (HPV) is responsible for about 99% cases of cervical cancer and in Portugal it is the 3rd most common in younger women. In this context, HPV type 16 and HPV type 18 are those that are most strongly associated with cervical cancer. The infection begins in the undifferentiated cells of the epithelium in the basal layer, and as they proliferate, the virus ensures genomic amplification and maintenance of replication as well as the establishment of infection in the most superficial cells of the epithelium. Because of the infection, benign clinical manifestations may develop, such as warts on the skin, anogenital warts or malignant manifestations, such as cervical cancer, among others. Most of the time, the immune system can ensure regression of the infection. However, in some cases, particularly in infections by high-risk HPVs, and with the direct intervention of the viral proteins E5, E6 and E7, the virus is able to guarantee the escape to the immune system, helped by the fact that the infection is intraepithelial and thus no viremia nor inflammatory response is triggered. Evasion of the immune system, coupled with the deregulation of viral E6 and E7 proteins (which is a consequence of the phenomenon of integration of viral genetic material into the host genome), has repercussions at the level of the normal cell cycle, which generates instability that can cause the development of cervical cancer. The diagnosis involves performing cytology, which reveals great specificity, and HPV molecular diagnostics tests that have the advantage of increased sensitivity compared to the previous method. Regarding prevention and treatment, the vaccine currently marketed in Portugal is Gardasil® 9, which has very promising values for effectiveness in prevention. In turn, the treatment is applied depending on the clinical manifestations that the patient has or depending on the stage of cervical cancer in which he is.
Human papillomavirus (HPV) is responsible for about 99% cases of cervical cancer and in Portugal it is the 3rd most common in younger women. In this context, HPV type 16 and HPV type 18 are those that are most strongly associated with cervical cancer. The infection begins in the undifferentiated cells of the epithelium in the basal layer, and as they proliferate, the virus ensures genomic amplification and maintenance of replication as well as the establishment of infection in the most superficial cells of the epithelium. Because of the infection, benign clinical manifestations may develop, such as warts on the skin, anogenital warts or malignant manifestations, such as cervical cancer, among others. Most of the time, the immune system can ensure regression of the infection. However, in some cases, particularly in infections by high-risk HPVs, and with the direct intervention of the viral proteins E5, E6 and E7, the virus is able to guarantee the escape to the immune system, helped by the fact that the infection is intraepithelial and thus no viremia nor inflammatory response is triggered. Evasion of the immune system, coupled with the deregulation of viral E6 and E7 proteins (which is a consequence of the phenomenon of integration of viral genetic material into the host genome), has repercussions at the level of the normal cell cycle, which generates instability that can cause the development of cervical cancer. The diagnosis involves performing cytology, which reveals great specificity, and HPV molecular diagnostics tests that have the advantage of increased sensitivity compared to the previous method. Regarding prevention and treatment, the vaccine currently marketed in Portugal is Gardasil® 9, which has very promising values for effectiveness in prevention. In turn, the treatment is applied depending on the clinical manifestations that the patient has or depending on the stage of cervical cancer in which he is.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2020, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
Vírus do papiloma humano Cancro do colo do útero Oncoproteínas E6 e E7 Desenvolvimento da infeção Gardasil 9 Mestrado integrado - 2020