Reply

We thank Thom and colleagues for their letter addressing human papilloma virus (HPV) in focal cortical dysplasia (FCD) and other epilepsy-associated brain pathologies. They suggest that what was previously reported as the HPV E6 oncoprotein in FCDIIB is “a cross-reaction with an as-yet unidentified neuroglial protein.” We appreciate their findings, because validation or refutation of the previous findings of HPV in FCD and glioblastoma has important public health relevance. However, several issues limit the conclusions of Thom et al, including a very small sample size, a limited description of experimental methods, incomplete experimental approaches to validate their claims, and most importantly, a failure to identify the proposed neuroglial protein. Furthermore, their report does not adequately explain the detection of the HPV viral capsid protein L1 in FCD. If the E6 oncoprotein detection is artifactual or nonpathogenic, then L1 should not be detected, because L1 and E6 are entirely nonhomologous proteins encoded by distinct genes in the HPV genome. It is puzzling that both L1 and E6 would be expressed in FCD as experimental artifact. The theory that an in utero viral infection plays a pathogenic role in brain malformations is not new and there is evidence, for example, that cytomegalovirus can cause pachygyria and smaller focal malformations. As we stated previously, the detection of E6 suggests an association between HPV and FCD but does not prove HPV pathogenicity in FCD, and further comprehensive studies are warranted to critically assess existing data sets. Until adequately powered studies are published, we stand by our original report.