Vaccination Against Cervical Cancer: Hopes and Realities

Globally, carcinomas of the anogenital tract, in particular cervical cancer, remain some of the most common cancers in women, cervical cancer represents the second most frequent gynecological malignancy and the third leading cause of cancer-related death in women worldwide. The causal relationship between human papilomavirus (HPV) infection and anogenital cancer has prompted substantial interest in the development of both preventive and therapeutic vaccines against high-risk HPV types. In the past decade, several groups have shown encouraging results using experimental vaccination systems in animal models and these results have led to several current prophylactic and therapeutic vaccine clinical trials in humans. Prophylactic vaccination focuses on the induction of high titer neutralizing antibodies that are potentially protective against incident and persistent HPV infection. Two major phase II clinical trials conducted by pharmaceutical companies have demonstrated that their vaccines have 100% efficacy in preventing persistent viral DNA and its associated cellular abnormalities; however, whether they induce long-lasting protective immunity is yet to be determined. At least one US FDA approved prophylactic vaccine targeting the two most common high-risk HPVs is expected to be on the market within the next 2-3 years. Nevertheless, significant reductions in the frequency and onset of cytologic screening and incidences of HPV-related lesions are not expected to become apparent for decades due to the fact that there will be women who are already infected with HPV, the long latency period between infection and development of high-grade lesions, and lesions associated with other high-risk HPV types not being included in the vaccines. Therapeutic vaccines aim to control HPV-associated malignancies by stimulating cellular immune responses that target established HPV infections via viral proteins. Progress in the field of HPV immunotherapy has remained elusive, with clinical trials being limited to small numbers of patients. Potential treatment of precancerous lesions is unique to HPV-associated infection and cancer because of cytologic monitoring and HPV typing. Unlike more common surgical treatments for cervical lesions, active immunotherapy has the potential to address HPV persistence as the cause of lesion development in addition to leaving the patient with long-term immunity that can be reactivated if and when the patient becomes reinfected.