Genetics Unit, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Address for correspondence: Apiwat Mutirangura, Genetics Unit, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. Voice: 66-2-256-4532; fax: 66-2-256-4534.
mapiwat{at}chula.ac.th
Following reports describing circulating tumor DNA, serum/plasma
viral nucleic acid has shown its potential as a new diagnostic
target in cancer. In the majority of examples of viral carcinogenesis,
the viral genome is consistently present in certain tumors and
serves as an effective marker. This article reviews recent findings,
proposes possible mechanisms, and examines the potential clinical
application of serum/plasma Epstein-Barr virus (EBV) DNA in
nasopharyngeal cancer (NPC) and human papillomavirus (HPV) DNA
in cervical carcinoma (CC). These tumors share a DNA viral etiology
and present similar histopathological findings. However, plasma
EBV and HPV DNA are distinct in several aspects, including incidence,
mechanism of release from tumor, and clinical application. Both
circulating cell-free EBV and HPV DNA reveal the same viral
type as their matched tumors, indicating both are derived from
the neoplastic tissue. Plasma viral DNA incidence and copy number
are high in NPC, but low in HPV-associated cancers. Whereas
much EBV DNA in NPC is episomal, the resistance to DNase treatment
of serum EBV DNA and evidence confirming lytic EBV replication
in NPC suggest that a reasonable proportion of plasma EBV DNA
is virions. On the contrary, plasma HPV genomes, as in CC, integrate
into host chromosome. Plasma EBV DNA copy number, by quantitative
PCR, is related to tumor mass, predicts prognosis, measures
immediate response to treatment, and is useful in early detection
of recurrence. Plasma HPV DNA, on the other hand, is associated
with and can be considered as an early tumor marker for distant
metastasis.
