Chapter 5: Viral and host factors in human papillomavirus persistence and progression.

Understanding the interdependent roles that host and viral factors play in cervical cancer pathogenesis is important for distinguishing women at the highest risk of human papillomavirus (HPV) persistence and progression to cervical cancer. Ongoing research on viral factors such as viral variants is providing important clues regarding HPV oncogenesis; the comprehensive characterization of the HPV genome and the function of viral genes by HPV type and variant will further this understanding. Although the biologic importance of viral integration and viral load measurements in cervical neoplasia is still being debated, available data are difficult to interpret because of methodologic limitations; to sufficiently address the importance of these events will require further methods validation and subsequent application in epidemiologic studies. Continued and expanded investigation of host immune responses-humoral, cellular, and innate immunity-should specifically address the outcomes of HPV persistence and progression to cervical cancer. Molecularly based assays paired with functional assays will be integral toward the identification and validation of key immune pathways and genes specifically relevant to cervical cancer pathogenesis. Novel technologies such as gene expression microarrays will further allow comprehensive identification of relevant genes that are important at various stages of cervical pathogenesis. The study of viral and host factors will undoubtedly lead to markers that may hold diagnostic and/or prognostic value; the clinical validity and utility of these molecular events will, therefore, need to be carefully assessed before implementation in a population setting.