Margaret F. Duggan-Keen, Michael D. Brown, Simon N. Stacey and Peter L. Stern

Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX , United Kingdom

Received 7/21/98 Accepted 9/22/98

2.INTRODUCTION: WHY HPV VACCINES?

Papillomaviruses (genus Papillomavirus of the Papovaviridae family) are associated with cutaneous or mucosal benign and malignant lesions in many species including humans. Over 95 types of human papillomaviruses (HPV) have been classified on the basis of DNA sequence homology, with the latter correlating with biological behavior and tissue tropism (1). For example, HPV 6 or 11 are found in benign anogenital warts which although not life threatening may be refractory to conventional treatment and frequently reoccur. These HPV types also cause recurrent laryngeal papillomas in young children, with frequent laser surgical ablation necessary to maintain an open airway (2). This type of HPV infection can be associated with considerable morbidity but rarely with malignancy. Immunological approaches to treatment of HPV associated benign lesions would clearly be very useful.

The evidence for the association of certain HPV types with the etiology of cervical neoplasia is firmly established, with HPV detected in up to 98% of all cervical cancers (3-5). Of the fifteen HPV types isolated from cervical carcinomas, HPV16 and HPV18 are most frequently detected. Cervical cancer is the second most common cause of cancer related death in women, and in some developing countries, it accounts for the highest cancer mortality (6). This malignancy is preceded by dysplastic precursor lesions which can be histologically classified (cervical intraepithelial neoplasia, CINI-III) on the basis of progressive cellular atypia and disturbed epithelial architecture. HPV prevalence rates of up to 70% in women with CINI and 75-100%for CINII/III have been reported (7-9). Cervical screening programs exist to reduce incidence, morbidity and mortality from cervical cancer, and they have had a measurable effect in some Western countries (10-13). However such programs will not eliminate HPV, due to the occurrence of asymptomatic infection, and they are also costly and difficult to implement in developing countries. A strategy for management of cervical neoplasia world-wide could be the development of prophylactic and/or therapeutic HPV vaccines.

This review will discuss the natural history of HPV infection, viral immunity and the clinical course of resultant disease as the background to the effective design and use of HPV vaccines for protection or therapy.