Molecular pathogenesis, detection and clinical management of pre-invasive cervical lesions

The major public health burden of cervical cancer and its associated lesions warrants the development of effective preventive measures and successful therapies. Cervical cancer is the second most common female cancer worldwide, with approximately 493,000 diagnoses and 270,000 deaths annually. The disease can be detected early by cervical cytology in the pre-malignant phase, in the form of high-grade squamous intraepithelial lesions, and treated by a variety of methods including loop electrosurgical excision procedure. As human papillomavirus (HPV) has been identified as the major causative agent of cervical dysplasia and cervical cancer, HPV DNA testing and genotyping are also valuable in enhancing the sensitivity and specificity of cervical cancer screening. Advances in the understanding of HPV pathogenesis have led to the concept that persistent infection with high-risk HPV (hrHPV) genotypes is recognized as a necessary though not sufficient step in causing cervical cancer. This has led to the identification of tumor-promoting markers that may be required in cervical carcinogenesis. Further investigation of these markers may potentially be useful for risk stratification in screening. The knowledge of HPV virology and its role in cervical carcinogenesis leads to the potential prevention and treatment of cervical cancer. The current status of HPV vaccines is also discussed.