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Published on: August 16, 2024
No evidence for human papillomavirus infection in focal cortical dysplasia IIb
Roland Coras1, Klaus Korn, Christian G Bien
1Department of Neuropathology, University Hospital Erlangen, Erlangen.
Objective:
The etiology of focal cortical dysplasia type IIb (FCDIIb) remains enigmatic in patients suffering from drug-resistant epilepsy, and an aberrant activation of the mammalian target of rapamycin complex 1 signaling pathway (mTORC1) was detected in this developmental brain malformation. Recently, the human papillomavirus (HPV) oncoprotein E6 has been identified as a potent activator of mTORC1, and HPV16 E6 has been described to persist in balloon cells obtained from surgical FCDIIb specimens. Although this observation was replicated by an independent second report, it contradicts current knowledge of HPV biology. HPV infects the squamous or mucocutaneous epithelium; hematogenic spread into other tissues has not been observed. In addition, brain carcinogenesis has never been reported in FCDIIb patients. Herein, we have tried to confirm 2 previous reports of HPV16 E6 infection using an independent series of 14 surgical specimens with histopathologically confirmed FCDIIb.
Methods:
Snap-frozen FCDIIb specimens were tested for HPV DNA using the primer set for amplification of the complete E6 reading frame of HPV16 and 3 other sets of primers (2 consensus primer sets detecting multiple HPV genotypes, and another primer set specifically used for HPV16). Furthermore, formalin-fixed and paraffin-embedded histopathological preparations were immunohistochemically analyzed using previously described antibodies directed against the HPV E6 oncoprotein.
Results:
All 14 FCDIIb specimens were negative for HPV DNA with all 4 primer sets. Antibodies directed against the HPV E6 epitope showed weak labeling of cytoplasm in balloon cells, as previously described in FCDIIb, but also in other cell populations.
Interpretation:
Our data did not confirm previously reported evidence for HPV16 detection in FCDIIb.
Insights
This study investigated human papillomavirus (HPV) in focal cortical dysplasia type IIb (FCDIIb), a cause of epilepsy. Researchers did not find evidence of HPV16 E6 in FCDIIb brain tissue, contradicting prior reports.
Area of Science:
- Neuroscience
- Oncology
- Virology
Background:
- Focal cortical dysplasia type IIb (FCDIIb) is a developmental brain malformation linked to drug-resistant epilepsy.
- Aberrant mammalian target of rapamycin complex 1 (mTORC1) signaling is implicated in FCDIIb.
- Previous studies suggested human papillomavirus (HPV) oncoprotein E6 activates mTORC1 and is present in FCDIIb balloon cells.
Purpose of the Study:
- To investigate the presence of HPV16 E6 in FCDIIb specimens.
- To confirm or refute previous findings suggesting HPV16 E6 infection in FCDIIb.
Main Methods:
- Analyzed 14 FCDIIb surgical specimens.
- Tested for HPV DNA using multiple primer sets, including specific primers for HPV16.
- Performed immunohistochemical analysis for HPV E6 oncoprotein using specific antibodies.
Main Results:
- No HPV DNA was detected in any of the 14 FCDIIb specimens using any primer set.
- Weak cytoplasmic labeling for HPV E6 was observed in balloon cells and other cell types, consistent with non-specific binding or cross-reactivity.
Conclusions:
- The study did not confirm previous reports of HPV16 detection in FCDIIb.
- The findings suggest HPV16 E6 is unlikely to be a causative factor in FCDIIb development.
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