The D2 and D3 sublineages of human papilloma virus 16-positive cervical cancer in Guatemala differ in integration rate and age of diagnosis

Hong Lou, Joseph F. Boland, Edmundo Torres-Gonzalez, Anaseidy Albanez, Weiyin Zhou, Mia K. Steinberg, Lena Diaw, Jason Mitchell, David Roberson, Michael Cullen, Lisa Garland, Sara Bass, Robert D. Burk, Meredith Yeager, Nicolas Wentzensen, Mark Schiffman, Enrique Alvirez Freites, Eduardo Gharzouzi, Lisa Mirabello, Michael Dean

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Human papillomavirus (HPV) 16 displays substantial sequence variation; four HPV16 lineages (A, B, C, and D) have been described as well as multiple sublineages. To identify molecular events associated with HPV16 carcinogenesis, we evaluated viral variation, the integration of HPV16, and somatic mutation in 96 cervical cancer samples from Guatemala. A total of 65% (62/96) of the samples had integrated HPV16 sequences and integration was associated with an earlier age of diagnosis and premenopausal disease. HPV16 integration sites were broadly distributed in the genome, but in one tumor, HPV16 integrated into the promoter of the IFN regulatory factor 4 (IRF4) gene, which plays an important role in the regulation of the IFN response to viral infection. The HPV16 D2 and D3 sublineages were found in 23% and 30% of the tumors, respectively, and were significantly associated with adenocarcinoma. D2-positive tumors had a higher rate of integration, earlier age of diagnosis, and a lower rate of somatic mutation, whereas D3-positive tumors were less likely to integrate, had later age of diagnosis, and exhibited a higher rate of somatic mutation. In conclusion, Guatemalan cervical tumors have a high frequency of very high-risk HPV16 D2 and D3 sublineages harboring distinct histology, which may help guide future therapeutic strategies to target the tumor and reduce recurrence.

Original languageEnglish (US)
Pages (from-to)3803-3809
Number of pages7
JournalCancer research
Volume80
Issue number18
DOIs
StatePublished - Sep 15 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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