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  • Torque Teno Virus Coinfection with High-Risk Human Papillomavirus in Cervical Cancer-Related Samples:

  • Mohammad Shayestehpour,1,*


  • Introduction: Cervical cancer remains one of the major malignancies associated with persistent viral infection, with high-risk human papillomavirus (HPV) representing the principal viral factor implicated in cervical carcinogenesis. Although the contribution of HPV to malignant transformation has been extensively investigated, less is known about the potential significance of additional viral infections within the cervical microenvironment. Torque Teno virus (TTV), a highly prevalent single-stranded DNA virus of the Anelloviridae family, has been detected in cervical specimens and reported in association with HPV infection, cervical lesions, and some HPV-related malignancies. The markedly different prevalence of TTV according to HPV status may provide insight into the viral environment accompanying high-risk HPV infection. Therefore, this study investigated TTV prevalence in cervical specimens according to HPV infection status, particularly in women carrying high-risk HPV, to explore its potential relevance to the viral context of cervical carcinogenesis.
  • Methods: This case-control study evaluated 300 fresh cervical cytobrush specimens collected from women. The participants were divided into three groups: HPV-negative (n=100), low-risk HPV-positive (n=100), and high-risk HPV-positive (n=100). Following DNA extraction, HPV infection and genotypes were determined using a PCR-based assay. TTV DNA was detected using nested polymerase chain reaction with specific primers. The prevalence of TTV was subsequently compared among the three HPV groups using the chi-square test. Statistical analyses were conducted using SPSS, with P<0.05 considered statistically significant.
  • Results: TTV DNA was detected in 174 of 300 cervical specimens. Importantly, the distribution of TTV was strongly associated with HPV status. TTV DNA was identified in 28/100 (28%) HPV-negative samples, compared with 46/100 (46%) samples containing low-risk HPV. The highest prevalence was observed among high-risk HPV-positive samples, in which TTV DNA was detected in 96/100 specimens (96%). TTV prevalence was therefore significantly higher in HPV-infected women, including both low-risk and high-risk HPV groups, compared with HPV-negative women (P<0.0001). Moreover, TTV detection was significantly more frequent among high-risk HPV-positive specimens than among low-risk HPV-positive specimens (P=0.048). No significant relationship was identified between age and TTV infection. The particularly high frequency of TTV in specimens harboring high-risk HPV is of potential relevance to cervical cancer research because persistent high-risk HPV infection represents a fundamental component of cervical carcinogenesis. Previous evidence cited in the study has also documented TTV or related anellovirus detection in cervical intraepithelial neoplasia and cervical cancer specimens, including a higher TTV prevalence reported among HPV-positive women with cervical cancer. However, these observations do not establish TTV as a carcinogenic virus.
  • Conclusion: The findings demonstrate a pronounced association between TTV and HPV infection in cervical specimens, with an exceptionally high TTV prevalence among samples containing high-risk HPV. From a cancer perspective, this pattern suggests that TTV may be an important component of the viral milieu associated with high-risk HPV infection and HPV-related cervical disease. Nevertheless, the present study establishes an epidemiological association rather than a causal relationship between TTV and cervical cancer. Whether TTV contributes to HPV persistence, modifies host immune responses, influences progression from HPV infection to cervical precancerous lesions, or affects malignant transformation remains unclear. Future longitudinal and molecular studies should investigate TTV–HPV interactions in women with cervical intraepithelial neoplasia and cervical cancer and determine whether TTV has potential value as a biomarker of HPV-associated cervical malignancy or disease progression.
  • Keywords: Cervical Cancer; Human Papillomavirus; High-Risk HPV; Torque Teno Virus

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