Human papillomavirus in anogenital cancer, with special reference to the viral capsid

Infection with the oncogenic types of Human Papillomavirus (HPV), particularly HPV type 16, is the major cause of anogenital dysplasias, which are precursor lesions of anogenital cancers. Studies of the HPV capsid are of interest, since HPV capsids are attractive candidates for cancer-preventive vaccines, since detection of viral capsids in clinical specimens can be used to monitor viral infectivity and spread and since HPV capsid seropositivity is a useful epidemiological marker of HPV exposure.

In the present study, the antigenic structure of the HPV16 capsid was determined and the role of HPV16 infection in anal cancer investigated. A method for sensitive and specific detection of HPV DNA in histological sections by in situ hybridization using probes labeled with digoxigenin was developed. HPVDNA was detected in anal cancers by in situ hybridization. The antigenic and immunogenic epitopes of the HPV capsid proteins were defined and their exposure on HPV particles and their cross-reactivity between HPV types was determined. Monospecific antibody reagents against the defined epitopes, useful for detection, quantitation and characterization of HPV particles in clinical specimens were developed. The HPV antibody response among anal cancer patients was characterized. HPV16 capsid seropositivity was found among more than half of anal cancer patients, but only among 4% of healthy controls. Since HPV16 capsids eropositivity is a marker of viral exposure, the results indicate that HPV infection is a risk factor for anal cancer. HPV16 infection was estimated to confer a 30-fold excess risk for anal cancer. HPV capsids containing both the major and minor HPV capsid proteins were produced using a recombinant Semliki Forest virus (SFV), which allowed the production of HPV capsids in mammalian cells. Such capsids may closely mimic the biological properties of native viruses.

In summary, HPV capsids have been produced and the antigenic structure of the capsid determined. The present study also found a strong link between HPV and anal cancer, lending further support to the concept that prophylactic HPV vaccination using HPV capsids may prevent anogenital cancers.