HHV-6B DNA associated with worse clinical outcomes in high grade serous epithelial ovarian cancer

Multiplex assay for 113 viruses in tumor tissue finds six viruses, including HHV-6B, linked to reduced overall survival.

Several viruses are clearly oncogenic, including human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein-Barr virus (EBV), and Merkel cell virus.  No virus has been clearly linked to ovarian cancer, particularly the most common type: serous epithelial ovarian cancer.

Investigators from the Moffitt Cancer Center and Research Institute in Tampa, Florida, used a multiplex assay to look for the presence of 133 human viruses in tumor specimens from 98 patients with high-grade serous epithelial ovarian cancer. In 46/98 (45.9%) of patients, specimens contained at least one virus.  Then the clinical outcome (overall survival curves) in people whose specimens contained each virus were compared to the outcomes of those whose specimens did not contain the virus.

Six of the 113 viruses were associated—all adversely—with clinical outcomes: Epstein-Barr virus 1, Merkel cell polyomavirus, HHV-6B, and human papillomaviruses 4, 16 and 23.  When one of these viruses was present, median overall survival was significantly decreased (22 months vs. 44 months in those without one of the viruses, P<0.0001).  This adverse association was found in women younger than 70 years old, but not in women 70 years or older.  Survival curves for women whose tumor specimens contained one of these six viruses, and those whose tumors did not, are compared in Figure 1.

Figure 1: Kaplan Meier curves portraying overall survival for cases with tumor specimen having a virus of interest (VOI) versus no VOI. The median overall survival for cases with VOI was 22 months (15–35 months) versus 44 months for cases without VOI (31–70 months). Log-rank P < 0.0001.

This study did not attempt to identify which cell types in the tumor tissue contained the viral DNA.  With a ubiquitous, lymphotropic virus like HHV-6B, it is possible that the DNA signal came from white blood cells in the tissue, not from the tumor cells or adjacent ovarian cells.

Also, the critical question in interpreting the results of this study is whether the viral DNA found in ovarian cancer tumor samples is an inactive player that homes to the tumor tissue, or whether the virus found in the tumor tissue alters the host-tumor microenvironment so as to adversely affect the clinical outcome.  Some prior evidence indicates that viruses in tumor tissue—while they may have had no role in generating the malignant cells—can sometimes adversely diminish the immune response to those malignant cells.

HHV-6B was the only virus among the six that has not been designated as directly oncogenic. However, some evidence indicates that HHV-6 may play a supportive role—along with other viruses including EBV and HPV—in the development of several cancers including the nodular sclerosis form of Hodgkin lymphoma, glial tumors, oral cancers and gastrointestinal cancer (Eliassen 2018).

In summary, this report raises the possibility that some viruses may be present in some high-grade serous epithelial ovarian cancers, and that their presence may somehow adversely affect survival. One of these viruses may be HHV-6B. These results are sufficiently provocative that further studies overcoming the limitations of this study are in order.

Read the full article: Robertson 2023