Additionally, in certain populations of women, a combined negative pap smear and HPV test allows women to avoid rescreening for another 3 years. This is because there is a greatly improved sensitivity with negative concurrent testing, and these women can be reassured that their risk of unidentified severe dysplasia or cancer is extremely low.
To date, more than 100 HPV types have been characterized. These have been divided into risk categories based upon their association with high grade dysplasia and carcinoma. HPV type 16 confers the greatest risk and is detected in almost 50% of squamous cell carcinomas of the cervix. During acute infection, the expression of viral genes is restricted to differentiated epithelial cells which have lost the ability to replicate. The virus exists in a circular episomal form that replicates outside of the host DNA. Under certain circumstances, and required for the development of high grade dysplasia and carcinoma, the virus integrates into the host DNA. High grade cervical dysplasia is initiated by deregulated expression of viral oncogenes in replicating epithelial basal cells. Viral proteins (E6 and E7) induce unchecked cellular signaling, have antiapoptotic effects, and ultimately allow accumulation of chromosomal damage by bypassing the G1 growth arrest checkpoint during which time cells normally undergo DNA repair. Understanding the pathogenesis of HPV has allowed researchers to target specific genes required for DNA replication which are induced and over-expressed in this pathway. Protocols will soon be underway for an exciting new marker, ProExC, which is associated with aberrant S-phase induction and is readily identified by immunohistochemistry in cells with high grade dysplasia.
A crowning achievement of the scientific research into HPV and its oncogenesis has been the recent development of a vaccine. A break-through advance 15 years ago was the creation of HPV-like particles in the lab. These were non-infectious, but did cause an impressive immune response. Subsequently, in 2002, researchers ran a double-blinded study of a HPV-16 vaccine involving over 2000 women, and followed them for 17 months. Their data, reported in the New England Journal of Medicine, found that the vaccine was an enormous success: it was 91% efficacious in preventing transient infections, 100% efficacious in preventing persistent infection, and, most importantly, 100% efficacious in preventing cervical dysplasia.