The Fight Against Cervical Cancer

Globally, cervical cancer is one of the most deadly forms of cancer affectingwomen—killingmore than 270,000 people every year. Themajority of these deaths (85%, according to theWHO) occur in developing countries. A global health priority, therefore, is to provide low-cost, highly effective cervical cancer prevention, detection, and control options to all women who need them. The human papillomavirus (HPV) family is a group of about 150 related viruses, a subset of which is thought to be responsible for the majority of cervical cancer cases. One of themost successful translational achievements in cervical cancer research in recent years is the development of highly effective preventative vaccines which directly target these oncogenic HPV strains. The bivalent vaccine Cervarix(r) (specific for HPV-16 and -18 strains) and the quadrivalent vaccine Gardasil(r) (which is additionally specific for HPV-6 and -11) contain viral L1 proteins from these strains, which are able to self-assemble into virus-like particles (VLPs). Recently, Gardasil(r) 9 has been approved by the United States FDA which will contain an additional 5 strains of HPV not currently covered by available vaccines. These vaccines induce antibody responses against HPV, but do not contain any of the viral genomic DNA present in natural viruses and, therefore, are not able to establish an infection. Available data indicate that these vaccines are highly effective at preventing precancerous cell induction in women, and since their introduction, global HPV infection rates appear to be declining. Although these prophylactic vaccines are highly effective at preventing new infections, neither vaccine is capable of inducing immune responses against established HPV infections. A major healthcare goal, currently, is to develop therapeutic approaches to resolving potentially cancerous HPV lesions (otherwise known as cervical intraepithelial neoplasia (CIN), or cervical dysplasia). Several approaches are underway, including a therapeutic vaccine which is likely to work by inducing an adaptive T cell-mediated response against the viral E6 and E7 proteins, which are expressed in these lesions. Several drugs are also being explored, including an antibody (bevacizumab) against vascular endothelial growth factor (VEGF), whichmay help patients by limiting the growth of new blood vessels to the cancer. Clinical trials are underway to test whether chemotherapy drugs or immune checkpoint inhibitors such as ipilimumab may work well in combination with radiation therapy. Autologous T cell transfers, where the patients own immune cells are