Acerca del cáncer cervicouterino como un importante problema de salud pública / About uterocervical cancer as an important public health problem

El cáncer se presenta como un importante problema de salud, dada la alta morbilidad y mortalidad que produce. Es uno de los procesos más complejos de la naturaleza y resulta el más complicado en la esfera de la medicina por su origen multicausal, la complejidad de sus mecanismos patogénicos y la variedad de formas y tipos que pueden originarse en el ser vivo. El objetivo de este trabajo es ofrecer información útil y actualizada acerca del cáncer cervicouterino. Esta enfermedad es prevenible y curable y se relaciona con la aparición del cáncer en vagina, cuello uterino, vulva y ano; en las mujeres se ha demostrado que la infección por el virus del papiloma humano es un factor de riesgo para su desarrollo. En la actualidad existen y se comercializan en el mundo dos tipos de vacuna, lo que se considera uno de los mayores avances en la medicina preventiva moderna. La aplicación de estas vacunas profilácticas contra el virus del papiloma humano podría reducir la incidencia y mortalidad por cáncer cervicouterino. Esta enfermedad constituye una de las entidades con más impacto y repercusión sobre la salud femenina, particularmente en las mujeres jóvenes. Está considerada una enfermedad emergente desde hace escasos años y sus consecuencias sociales, humanas y económicas lo convierten en un problema importante de salud pública y de la humanidad

Cancer represents an important health problem due to its high morbidity and mortality. It is one of the most complex processes of nature and the most complicated in medicine because of its multiple cause origin, the complexity of its pathogenic mechanisms and the variety of forms and types that may adopt in the subject alive. The objective of this paper was to provide useful and updated information on the uterocervical cancer. This disease is preventable and curable; it is related to the occurrence of cancer in the vagina, the uterine neck, the vulva and the anus. It has been proved that human papiloma virus infection is one of the risk factor for cancer in females. Two kinds of vaccine are marketed worldwide, and this is considered as one of the major advances in the modern preventive medicine. The administration of these prophylactic vaccines against the human papiloma could reduce the incidence and the mortality cause by uterocervical cancer, one of the diseases with high impact and repercussion on the female health, particularly in young females. It is considered an emerging disease and its human, social and economic consequences turn it into an important public health problem for mankind

Desarrollo de una vacuna profiláctica de segunda generación contra el papilomavirus humano / Development of a second generation prophylactic vaccine against human papillomavirus

Los papilomavirus humanos (HPV) son el agente etiológico del cáncer cervical (CC), la segunda causa de muerte por cáncer en mujeres. Se estima que medio millón de nuevos cánceres se diagnostica cada año, ocurriendo la mayoría de ellos en países en vías de desarrollo debido a la ausencia o ineficiencia de los programas masivos de detección temprana. Recientemente se han introducido en el mercado dos vacunas profilácticas contra las principales cepas oncogénicas de HPV, la cepa 16 y 18, responsables por el 80% de todos los CC. Estas vacunas se obtienen en forma recombinante y han demostrado ser extremadamente seguras y eficaces. Sin embargo, su impacto inmediato en la incidencia de la infección por HPV en países en vías de desarrollo será mínimo, debido principalmente al alto costo de las mismas. Existe la necesidad de contar con vacunas de segunda generación, de bajo costo y de aplicación masiva que permitan disminuir sensiblemente el número de CC en la población. Con este objetivo hemos desarrollado una plataforma de expresión recombinante que permite obtener partículas tipo virus (VLPs) con las cuales es posible formular vacunas efectivas y accesibles contra la infección por HPV.

Human papillomaviruses (HPV) are the etiologic agent for cervical cancer (CC), the second cause of cancer death in women worldwide. It is estimated that half a million new cases are diagnosed each year, mostly in developing countries due to the lack of massive programs for early detection of the virus. Recently, two prophylactic vaccines against the main oncogenic HPV types 16 and 18 (responsible for 80% of CC) have been introduced into market. Both of these vaccines, obtained as recombinants, have been shown to be safe and effective; however, their high cost works against its immediate impact in the incidence of HPV infection in developing and low-income countries. There is a need to have in hand second generation, low cost vaccines of massive use that will decrease CC cases in a large extent. With this in mind, we have developed a recombinant expression platform that allows us to obtain virus-like particles (VLPs) to formulate both effective and accessible vaccines against HPV infection.

Vaccination with a Human Papillomavirus (HPV)-16/18 AS04-Adjuvanted Cervical Cancer Vaccine in Korean Girls Aged 10-14 Years

The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has been demonstrated to be highly efficacious and immunogenic with a favorable safety profile. This study assessed the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10-14 yr. This multi-center, observer-blind trial randomly assigned 321 healthy girls to receive three doses (0, 1, 6-month schedule) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis A vaccine. Immunogenicity against vaccine antigens was assessed one month post-Dose 3. Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. In the according-to-protocol analysis, all initially seronegative subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted at Month 7, with a peak geometric mean titer (GMT) that was 600-fold higher than the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400-fold higher than the natural infection titer of 22.6 EU/mL for HPV-18. The vaccine was well tolerated with no increase in reactogenicity with subsequent doses and no reports of vaccine-related SAEs. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated in Korean girls aged 10-14 yr.

Cervical cancer prevention & the role of human papillomavirus vaccines in India.

Human papillomavirus (HPV) is a necessary cause of cervical cancer, the leading cause of cancer deaths among Indian women. Current screening and prevention programs based on cytology have not been effective in reducing the disease burden. Two vaccines are now available for primary prevention. They generate neutralizing antibodies to HPV capsid protein. The vaccines have been shown to confer nearly 100 per cent protection against cervical pre-cancers and genital warts caused by HPV types 16/18 in HPV naïve population with few or no side effects. Though there is some cross-protection, around 30 per cent of cervical cancers will not be prevented by the vaccine. Vaccination and screening, which are complementary and synergistic, now constitute the new paradigm for prevention of this disease.

Immune responses to human papilloma viruses.

HPV infection in the genital tract is common in young sexually active individuals, the majority of whom clear the infection without overt clinical disease. However most of those who develop benign lesions eventually mount an effective cell mediated immune response and the lesions regress. Regression of ano-genital warts is accompanied histologically by a CD4+ T cell dominated Th1 response; animal models support this and provide evidence that the response is modulated by CD4+ T cell dependent mechanisms. Failure to develop effective CMI to clear or control infection results in persistent infection and, in the case of the oncogenic HPVs, an increased probability of progression to CIN3 and invasive carcinoma. The central importance of the CD4+ T cell population in the control of HPV infection is shown by the increased prevalence of HPV infections and HGSIL in individuals immunosuppressed as a consequence of HIV infection. The prolonged duration of infection associated with HPV seems to be associated with effective evasion of innate immunity as reflected in the absence of inflammation during virus replication, assembly and release, and down regulation of interferon secretion and response thus delaying the activation of adaptive immunity. Serum neutralising antibody to the major capsid protein L1 usually develops after the induction of successful cell mediated immunity and these antibody and cell mediated responses are protective against subsequent viral challenge in natural infections in animals. Prophylactic vaccines consisting of HPV L1 VLPs generate high anti L1 serum neutralizing antibody concentrations and in clinical trials have shown greater than 95 per cent efficacy against both benign and neoplastic genital HPV associated disease. These vaccines are delivered intramuscularly and therefore circumvent the immune evasion strategies of the virus.

HPV vaccination: the beginning of the end of cervical cancer? - A Review

Human papillomavirus (HPV) is responsible for all cases of cervical cancer, as well as a great percentage of other anogenital tumors and oropharyngeal tumors. Since the main etiologic factor for these diseases is a virus, prophylactic measures are the best way to reduce the burden caused by the infection and associated disease. This review brings up to date information on the two commercially available prophylactic HPV vaccines against HPV, as well as presenting the ongoing research on HPV peptide, protein and dendritic cell based therapeutic vaccines.

Recent Concepts of Human Papillomavirus Vaccine

Two prophylactic human papillomavirus (HPV) vaccines against types 6, 11, 16 and 18 have shown great promise in clinical trials with recent results demonstrating 100% efficacy against persistent HPV infection and development of cervical intraepithelial neoplasia up to five years of follow-up. Published data from the phase-IIb and III trials thus far indicate that the prophylactic HPV L1 virus-like particle vaccine is safe and well-tolerated. It offers HPV-naive women a very high level of protection against HPV persistent infection and cervical intraepithelial lesions associated with the types included in the vaccine. HPV vaccination should be also offered to girls before onset of sexual activity. But there are still questions about several issues of HPV prophylactic vaccination. Prolonged clinical trials should be performed for demonstration of these remaining questions. Finally, prophylactic vaccines against HPV will certainly reduce the incidence of the risk of developing cervical cancer.