Since its discovery, HHV-6 has been studied in the context of lymphoproliferative disorders and various types of cancer. Several obstacles, particularly the ubiquitous nature of the virus, have made it difficult to determine exactly how HHV-6 might, or might not, be involved in tumor development.
Investigators from Japan looked at HHV-6 and HHV-7 DNA levels in saliva to see if they might be biomarkers for cancer-related fatigue (CRF) in multiple myeloma patients.
Investigators at the National Cancer Institute found that HHV-6+ lymph nodes can be identified in biopsies from both lymphadenopathy and malignancies. They warn that failing to identify HHV-6 in these biopsies can lead to misdiagnosis in lymphoma cases.
Using a novel serological assay that can differentiate HHV-6A from HHV-6B, investigators found HHV-6A immediate early antibodies to be associated with an increased risk of non-Hodgkin lymphoma.
German investigators conducted a broad scale analysis of CD8 T cell responses to HHV-6B, identifying novel epitopes with potential for immunotherapy or vaccines. The strongest responses were directed against an epitope from IE-2.
The authors discuss how HHV-6 may contribute to the progression of reactive lymphoproliferative disorders by spurring a dysfunctional immune response.
A broadscale investigation of the ovarian cancer oncobiome using a microarray system PathoChip found HHV-6A sequences at or near genes associated with tumorigenesis in ovarian cancer tissue samples.
A team at University of Pittsburgh analyzed a large database of deep sequencing data from tumor and control tissues to look for viral sequences in 22 different cancers. They were surprised to find several herpesviruses in gastrointestinal cancers but not in control tissues.
A higher prevalence of inherited virus was found in patients
Investigators at Fred Hutchinson Cancer Center determined that transplant patients with inherited ciHHV-6 were twice as likely to develop acute graft vs host disease and three times more likely to develop high level CMV viremia. Transplant patients were also significantly more likely to have inherited ciHHV-6 than donors.
Italian investigators found that HHV-6 latency-associated gene U94, inserted in a HSV1 vector, inhibited the development of breast cancer, cervical cancer, and lung metastasis. It also impaired tumor driven angiogenesis.
Human papillomavirus 4 is a benign strain not associated with cancer. However, in a woman with inherited chromosomally integrated HHV-6A, a high grade vaginal squamous lesion developed rapidly. The authors warn that there may be a synergistic effect between HPV4 and iciHHV6A.
Investigators from the University of Ferrara, Italy have found evidence suggesting that high levels of U94 in ciHHV6 may predispose to the formation of marker chromosomes. A patient with diffuse large B-cell lymphoma positive for inherited chromosomally integrated HHV-6A and HHV-6A was also found in a marker chromosome, an abnormal piece of chromosome that is seen in some leukemia and lymphomas.
Investigators at Yale University warn that hypersensitivity-associated HHV-6 lymphadenopathy can have the same presentation as lymphoma.
Biopsies from patients with 5 types of lymphoproliferative disorders of the ocular adnexa, were found to contain HHV-6 DNA in 9 of 70 (12.9%) samples. While an overall detection rate of 12.9% is significant, HHV-6 was even more prevalent among those with benign lymphoproliferative disorders; HHV-6 was found in 22.7% of those with IgG4-related ophthalmic disease and 28.6% of those with orbital reactive lymphoid hyperplasia.
A group from the National Institute of Neurological Disorders and Stroke, NIH, has reported finding Epstein-Barr Virus (EBV) and HHV-6 but no cytomegalovirus (CMV) in astrocytomas, a brain tumor comprising approximately one quarter of all gliomas diagnosed. The group used digital droplet PCR (ddPCR), a technique that is highly precise but less sensitive than nested PCR and immunohistochemistry, techniques that have been used in previous studies.
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