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REVIEWS
PREVENTION OF CERVICAL CANCER THROUGH PAPILLOMAVIRUS VACCINATION
Ian H. Frazer
A subset of human papillomaviruses (HPVs) promote anogenital malignancy, including cervical cancer, and prevention and treatment strategies that reflect the causal role of HPV are being developed. Vaccines based on HPV virus-like particles induce genotype-specific virus-neutralizing antibody and prevent infection with HPV1. Persistent papillomavirus infection is required for the development of papillomavirus-associated cancer and, therefore, therapeutic vaccines are being developed to eliminate established papillomavirus infection. Such vaccines test principles for the growing field of tumour-antigen-specific immunotherapy. This article reviews progress in the field and draws conclusions for the development of future prophylactic and therapeutic viral vaccines.
HPV GENOTYPES
Human papillomaviruses (HPVs) are categorized into genotypes according to the extent of sequence divergence in genes that are conserved between different isolates (in particular the L1 capsid gene), and genotypes are organized into broad clades of related sequence and, in general, related biology.
Globally, cervical cancer is one of most common cancers in women, killing about 0.25 million women per year. Cervical cancer (BOX 1) is attributed to persistent infection with a high-risk subset of human papillomaviruses (HPVs) (TABLE 1), and is the first cancer recognized by the World Health Organization (WHO) to be 100% attributable to an infection2.At present, optimal treatment of cervical cancer combines surgery or radiotherapy with adjuvant chemotherapy, and delivers cure rates of almost 100% for locally invasive Federation of International Gynaecologists and Obstetricians (FIGO) stage 1 disease. Disease that has spread beyond the pelvis FIGO stage 4 is not generally regarded as curable, and many patients present with stage 4 disease in the developing world. Prevention and early detection of cervical cancer relies on cytology screening programmes, which have markedly reduced cervical cancer death rates where they are available. However, more than 80% of cervical cancer occurs in the developing world, where neither population-based screening nor optimal treatment is available. Further, present treatments and to a large extent present screening strategies do not acknowledge the viral aetiology of this common cancer.
The link between cervical cancer and HPV
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