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Published on: February 5, 2018
Type-specific detection and quantification of circulating tumor HPV DNA by digital PCR in surgically resected
Asami Matsunaga1,2, Miho Ogawa3, Akiko Kunita3
1Department of Obstetrics and Gynecology, Nihon University School of Medicine, Tokyo, Japan.
Objective:
Circulating tumor human papillomavirus (HPV) DNA (ctHPV DNA) has shown clinical utility in advanced cervical cancer; however, its role in surgically resected disease remains unclear. We evaluated the detectability and clinicopathological associations of ctHPV DNA in preoperative plasma from patients with surgically resected cervical cancer using digital polymerase chain reaction (dPCR).
Methods:
We analyzed 49 surgically resected cervical cancer patients. HPV genotyping of formalin-fixed paraffin-embedded tumor tissues was performed using both PGMY09/11 consensus PCR and novel genotype-specific dPCR assays targeting 6 high-risk HPV types (16, 18, 31, 39, 45, and 52). Plasma cell-free DNA was analyzed using dPCR for HPV genotypes. Associations between ctHPV DNA copy number and clinicopathological features were evaluated.
Results:
HPV genotypes were identified in 42 of 49 tumor tissues (85.7%), with dPCR showing superior sensitivity (95.8%) compared to the PGMY method (77.6%). ctHPV DNA was detected in 12 of 42 evaluable plasma samples (28.6%), and plasma genotypes were concordant with those of the corresponding tumor tissues. ctHPV DNA copy numbers were significantly higher in cases with lymphovascular invasion (p=0.034) and lymph node metastasis (p=0.010), but were not correlated with tumor size, stage, or histologic type. ctHPV DNA was more consistently detectable than PIK3CA hotspot mutations in plasma, supporting its robustness as a biomarker in liquid biopsy settings.
Conclusion:
This study highlights ctHPV DNA as a promising noninvasive biomarker in surgically resected cervical cancer. Its association with lymphovascular invasion and lymph node metastasis supports its potential role in preoperative risk stratification and personalized surgical planning.
