Detection and Phylogenetic Analysis of Torque Teno Virus in Salivary and Tumor Biopsy Samples from Head and Neck Carcinoma Patients

Abstract

Objectives: Because torque teno virus (TTV) has been implicated in tumorigenesis as a cocarcinogen, we studied TTV prevalence in saliva and biopsy samples from head and neck cancer (HNCC) patients, patients with premalignant lesions of oral cancer, and controls. We also wished to determine the TTV genotypes in HNCC patients. Methods: A seminested polymerase chain reaction (PCR) amplifying the N22 region of the TTV genome, as well as direct sequencing of PCR fragments, was used. Results: TTV prevalence was higher in HNCC patients (saliva: 27/71, 38%; tumor biopsy: 22/74, 30%) than in controls (saliva: 8/56, 14%; oral mucosa: 1/19, 5%). TTV prevalence was also high in patients with premalignant lesions of oral carcinoma (saliva: 9/18, 50%; biopsy: 5/21, 24%). By phylogenetic analysis, TTV belonging mostly to genotypes 1 and 2 was found in HNCC patients. In most of the cases, identical TTV strains were present in the biopsy and salivary sample of the same HNCC patient. In addition, the same TTV strain was detected in 2 laryngeal carcinoma biopsies obtained from 2 independent patients. Conclusions: Our data are compatible with the idea that TTV might act as a cocarcinogen in certain cases of HNCC. Alternatively, HNCC may facilitate either TTV replication or TTV entry into the saliva.

Detection of Interleukin 6 (IL-6) antigen in the head and neck carcinoma cells

“…In addition, the role of human papilloma virus (HPV) has been implicated as a possible cofactor, but the mechanism of action of this virus at HNSCC pathogenesis (in contrast to cervical carcinoma) still not exactly understood [43]. Also, the Epstein-Barr virus (EBV) seems to be somehow involved (at least for the development of SCC at nasopharynx), along with the Torque teno (TTV) and hepatitis C (HCV) viruses, which all may act as possible co-carcinogens increasing the risk of malignant transformation [44,45].…”

Development of an Immunoassay for Detection of Torque Teno Virus (TTV) Antibodies Using the N22 Expression Product from TTV Genotype 2

“…Firstly a high prevalence rate and secondly the highly heterogeneous nature of its DNA have raised a serious concern. Simultaneously, it is quite interesting to note an association of TTV with certain carcinomas/malignancies, indicating the chances of its DNA integrating with the human genome during the replication cycle [18]. However, no such conclusive report is available at this stage and therefore further studies on various aspects of this virus, including its role in disease causation, are required [20,38].…”

“…However, it is not clear whether these variants have some biological or pathogenic differences also [15]. Of course, few recent reports point to an association between genotypes/genogroups and the type of disease caused [17,18]. This needs further extensive investigation.…”

“…It has also been detected in various types of carcinoma including leukemia and colorectal cancer. However, the pathogenicity of TTV at present is unclear [7,18,20,26,27]. Due to the lack of available tissue-culture methods, TTV infection is often diagnosed on the basis of TTV-DNA detection by PCR.…”

Torque Teno Virus and Hepatitis: A review on correlation.

“…The low percentage of TTV infection in non-hepatic diseases have been postulated to have an association with less exposure to blood transfusion. The percentage of TTV infection among nonhepatic diseases were proven in few studies (Berkhouse & Gray, 2017;Hettmann et al, 2016;Kalkan et al, 2005) even though the majority of the percentage are not more than 50%. In contrast, the percentage of TTV infection detected among healthy individuals were surprisingly high (Hussain et al, 2012a;Koohi et al, 2012;Costa et al, 2015;Peng et al, 2015;Hsiao et al, 2016).…”