Humoral Immune Response Against Human Papillomavirus as Source of Biomarkers for the Prediction and Detection of Cervical Cancer.

Cervical cancer (CC) is one of the main causes of death among women of reproductive age. Although there are different tests, the disease tends to be diagnosed at late stages. In recent years, the use of complementary tests or sequential diagnostic tests has been implemented. Nevertheless, the results are variable and not conclusive; therefore, more studies for improving the usefulness of these tests in diagnostics are necessary. The human papillomavirus (HPV) infection has been associated with both benign and malignant proliferation of skin and mucosal tissues. Furthermore, some HPV types have been classified as high risk due to their potential to cause cancer, and HPV16 is most frequently associated with this disease. Although between 70% and 80% of precancerous lesions are eliminated by the host's immune system, there is no available test to distinguish between regressive lesions from those that could progress to CC. An HPV infection generates a humoral immune response against L1 and L2 capsid proteins, which can be protective and a response against early proteins. The latter is not a protective response, but these antibodies can be used as markers to determine the stage of the infection and/or the stage of the cervical lesion. Up to now, the humoral immune response resulting from the HPV infection has been used to study the biology of the virus and the efficacy of the HPV vaccines. Although there are no conclusive results regarding the use of these antibodies for diagnosis, we hereby review the actual panorama of the antibody response against the HPV proteins during the development of the disease as well as their possible use as biomarkers for the progression of cervical lesions and of CC.

Asociación entre la presencia de anticuerpos anti-Ras y anti-VPH16 E4/E7 y lesiones intraepiteliales del cérvix / Association between anti-Ras and anti-HPV16 E4/E7 antibodies with cervical intraepithelial lesions

OBJETIVO: Determinar si anticuerpos séricos contra E4, E7 y Ras pueden ser utilizados como marcadores de lesiones tempranas del cérvix uterino asociadas al virus del papiloma humano. MATERIAL Y MÉTODOS: Entre marzo de 1999 y abril de 2000 se realizó un estudio sero-epidemiológico de casos y controles en la clínica de displasias del Hospital General Doctor Gea González, en la Ciudad de México, en 116 muestras de suero para evaluar la presencia de anticuerpos anti-E4, E7 y Ras utilizando un ELISA de captura. Se estimaron razones de momios e intervalos de confianza de 95 por ciento RESULTADOS: Anticuerpos anti-E7 se asociaron a mujeres con lesiones NIC III, mientras que anticuerpos anti-E4 y anti-Ras fueron más frecuentes en lesiones NIC I-II. Al evaluar el perfil de anticuerpos que presentaron las mujeres, encontramos que a) anticuerpos contra dos proteínas predicen la existencia de una lesión NIC I-II, y b) la presencia de tres anticuerpos predicen una lesión NIC III. CONCLUSIONES: La detección de anticuerpos séricos contra E4, E7 y Ras en combinación con otras técnicas de diagnóstico, podrían ser de utilidad para detectar oportunamente a mujeres con lesiones tempranas asociadas al Virus del Papiloma Humano y en riesgo de desarrollar cáncer