Human Papillomavirus Load and Cervical Carcinoma

Sammanfattning: Human Papillomavirus (HPV) is a key factor in the development of cervical cancer. Out of the more than 100 known HPV types 13 are considered oncogenic. In addition to presence of the virus several other factors have been proposed to influence risk of cervical cancer. This thesis focuses on viral load and HLA class II alleles as risk factors for cervical cancer.To enable quantification of the most common oncogenic HPV types, a real-time PCR-based assay was developed and evaluated in terms of technical sensitivity and specificity.This assay was then employed on archival smears from 457 cases and 552 controls to assess associations between viral load and cervical carcinoma in situ (CIS). Whereas the data indicate a pronounced dose dependent effect of HPV 16 load on the risk of CIS, other HPV types only seem to increase CIS risk at higher viral loads. These effects were observed even when cytology indicated that cells were normal.We then investigated viral load as a risk factor for invasive cervical carcinoma (ICC) in a retrospective study comprising 139 cases and 550 controls. Viral load contributed similarly to the risk of ICC as to the risk of CIS.Finally, associations between HLA class II alleles, viral load and CIS were investigated. Carriers of the DRB1'1301 allele were less prone to infections and high viral loads of HPV 31 and -18/45. Moreover, DRB1'1301 had a protective effect against CIS among women infected by HPV 31 or -18/45. In contrast, carriers of DRB1'1501 and DQB1'0602 were more susceptible to infections and high viral loads of HPV 16.These results indicate that HPV load may have HPV-type specific effects on cervical cancer risk. Furthermore, HLA class II alleles may confer either susceptibility or protection against cervical cancer by acting on the HPV infections preceding tumor development.