Multi-scale Transcriptional Characterization of HPV16 and HPV18 in Cervical Cancer: Host Pathway Alterations and Links With Viral Gene Expression Programs
- 1Universidade de Sao Paulo
Abstract
High-risk HPV is central to cervical carcinogenesis, but whether individual genotypes drive distinct tumor biology or converge on a shared oncogenic state remains unclear. Profiling viral and host gene expression across two independent cohorts (n = 93; 76 HPV16, 17 HPV18), we show that HPV16- and HPV18-associated cervical cancers differ in host transcriptional programs. A 55-gene signature discriminated the two genotypes, and 293 genes were concordantly differentially expressed across cohorts. Pathway and transcription-factor activity inference organized these differences along genotype-specific axes: HPV16 tumors were enriched for epithelial polarity and RTK-RAS-MAPK signatures, with elevated inferred CDX2 regulon activity, a transcription factor not normally active in cervical epithelium, suggesting an aberrant lineage-identity program not previously linked to this genotype. HPV18 tumors instead showed metabolic reprogramming and inflammatory signaling (STAT3, HIF1A), alongside reduced CASP8 and increased FDX1 expression, a pattern consistent with sensitization to immunogenic cell death. Both genotypes also organized along a continuum of early-to-late viral gene expression correlating with distinct host pathways: extracellular-matrix and translation-related in HPV16, interferon/antiviral and cell-cycle/mitochondrial in HPV18, indicating that viral transcriptional state associates with host biology beyond genotype alone. These results point to candidate genotype-specific vulnerabilities that merit functional validation.
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BibTeX
@misc{ishihara2026multiscale,
title = {{Multi-scale Transcriptional Characterization of HPV16 and HPV18 in Cervical Cancer: Host Pathway Alterations and Links With Viral Gene Expression Programs}},
author = {M. A. Ishihara and M. M. Moro Valeriano and N. Oliveira and I. Mamede and L. Cavalcanti de Morais Gama and A. Ferreira Cunha and I. Maia Santos de Castro and F. Vasquez and M. Y. Nishiyama-Jr and J. C. Setubal and E. de Arruda Neto and R. Chammas and H. I. Nakaya},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.755713},
url = {https://www.biorxiv.org/content/10.64898/2026.09.30.755713v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Multi-scale Transcriptional Characterization of HPV16 and HPV18 in Cervical Cancer: Host Pathway Alterations and Links With Viral Gene Expression Programs
AU - M. A. Ishihara
AU - M. M. Moro Valeriano
AU - N. Oliveira
AU - I. Mamede
AU - L. Cavalcanti de Morais Gama
AU - A. Ferreira Cunha
AU - I. Maia Santos de Castro
AU - F. Vasquez
AU - M. Y. Nishiyama-Jr
AU - J. C. Setubal
AU - E. de Arruda Neto
AU - R. Chammas
AU - H. I. Nakaya
PY - 2026
DA - 2026/09/30
PB - bioRxiv
DO - 10.64898/2026.09.30.755713
UR - https://www.biorxiv.org/content/10.64898/2026.09.30.755713v1
AB - High-risk HPV is central to cervical carcinogenesis, but whether individual genotypes drive distinct tumor biology or converge on a shared oncogenic state remains unclear. Profiling viral and host gene expression across two independent cohorts (n = 93; 76 HPV16, 17 HPV18), we show that HPV16- and HPV18-associated cervical cancers differ in host transcriptional programs. A 55-gene signature discriminated the two genotypes, and 293 genes were concordantly differentially expressed across cohorts. Pathway and transcription-factor activity inference organized these differences along genotype-specific axes: HPV16 tumors were enriched for epithelial polarity and RTK-RAS-MAPK signatures, with elevated inferred CDX2 regulon activity, a transcription factor not normally active in cervical epithelium, suggesting an aberrant lineage-identity program not previously linked to this genotype. HPV18 tumors instead showed metabolic reprogramming and inflammatory signaling (STAT3, HIF1A), alongside reduced CASP8 and increased FDX1 expression, a pattern consistent with sensitization to immunogenic cell death. Both genotypes also organized along a continuum of early-to-late viral gene expression correlating with distinct host pathways: extracellular-matrix and translation-related in HPV16, interferon/antiviral and cell-cycle/mitochondrial in HPV18, indicating that viral transcriptional state associates with host biology beyond genotype alone. These results point to candidate genotype-specific vulnerabilities that merit functional validation.
ER -