Moreover, not all children infected with HPV-6 or -11 develop RRP. Researchers at the University of Mississippi Medical Center examined tonsillectomy specimens from 50 children undergoing tonsillectomy for hypertrophy or recurrent tonsillitis. Although none of the children showed evidence of RRP, one child did have HPV-11 infection. In an earlier survey of healthy children, researchers at the University of Iowa found that 9% of healthy children under the age of seven had evidence of oral HPV infection.
Explore This IssueOctober 2006
Given these patterns of disease, scientists are looking for host factors that make individuals susceptible to RRP. Already, several studies have shown that specific alleles of the major histocompatibility complex (MHC) are disproportionately represented in the RRP patient population relative to the population as a whole. However, because most people with those MHC alleles and HPV exposure do not develop RRP, the MHC factors cannot be the whole story.
Farrel J. Buchinsky, MD, PhD, a pediatric otolaryngologist at Allegheny General Hospital in Pittsburgh, and colleagues have launched a large multicenter genetic study to scan the genome for gene variants associated with RRP. Thus far, the team has enrolled 177 patients in the study, along with one or both parents. The idea behind the study is that any allele that increases susceptibility to RRP should be transmitted more frequently to the affected offspring than would occur by random chance. The researchers have performed a preliminary low-resolution genome scan-using just 6000 single nucleotide polymorphisms to mark the variation across the genome-on the first 60 patients, but found no hits. We now want to do the same thing, but instead of looking at 6000 spots, looking at 300,000 across the genome in a larger sample of patients, said Dr. Buchinsky. The problem is that it is extremely expensive and we are going to need additional funding before we can do it.
In the meantime, they are using a candidate-gene approach, looking to see if genes that have been previously implicated in RRP or an HPV-related condition, are segregating disproportionately between parents and children. Preliminary analysis showed no correlation between the EVER1 gene, which is responsible for susceptibility to epidermodysplasia verruciformis 1, a skin disease caused by HPV. The team is now looking more closely at EVER1 and EVER2, another gene involved in the same disease, and at the TAP-1 gene. The TAP-1 protein is required for efficient antigen presentation on immune cells and is known to interact with HPV E7 protein. The E7-TAP-1 interaction appears to decrease the amount of TAP-1 in the cell. Thus, researchers have hypothesized that certain TAP-1 alleles may help HPV evade immune detection in some individuals.