ABSTRACT
Human papillomavirus (HPV) infection is the most common sexually transmitted disease, with more than 80% of the population infected at some time in their life. In rare cases, this infection may lead to cervical cancer. Virtually all squamous cell carcinomas and the overwhelming majority of adenocarcinomas of the cervix are HPV positive. HPV integration in the genome will lead to inactivation of the p53 pathway and the Rb pathway. Integration is essential for the onset of cervical carcinogenesis, but is probably not sufficient for progression to invasive cervical cancers. It is likely that several cofactors, such as environmental, viral and host-related factors, are necessary for the development of cervical cancer. There are several similarities and differences between the two major histological types. This article will address the role of HPV in cervical carcinogenesis as well as the molecular biology involved in the process.
Subject(s)
Adenocarcinoma/virology , Carcinoma, Squamous Cell/virology , Papillomavirus Infections/complications , Sexually Transmitted Diseases, Viral/complications , Uterine Cervical Neoplasms/virology , Adenocarcinoma/blood supply , Apoptosis/physiology , Carcinoma, Squamous Cell/blood supply , Diet/adverse effects , Environmental Exposure/adverse effects , Female , Humans , Life Style , Neovascularization, Pathologic/complications , Papillomaviridae/pathogenicity , Retinoblastoma Protein/metabolism , Risk Factors , Sexual Behavior , Tumor Suppressor Protein p53/metabolism , Uterine Cervical Neoplasms/blood supplyABSTRACT
Persistent infection with one of the oncogenic human papillomavirus (HPV) types is a necessity for the development of cervical cancer. By HPV vaccination, cervical cancer could become a very rare disease. Two types of HPV vaccines can be distinguished: (i) therapeutic vaccines which induce cellular immunity targeted against epithelial cells infected with HPV and (ii) prophylactic vaccines inducing virus-neutralizing antibodies protecting against new but not against established infections. At present, several vaccines have been developed and tested in clinical trials. The vaccines are generally well tolerated and highly immunogenic. The current clinical data indicate that prophylactic vaccines are very effective against new persistent infections and the development of cervical intraepithelial lesions. The protection is type specific. However, the follow-up of the vaccination trials is still short. The effect of HPV vaccines on future cancer incidence will only be known after decades of follow-up. This article will address the status of recently terminated phase II and currently running phase III trials with prophylactic HPV vaccines.
