Detection of early human papillomavirus-associated cancers by liquid biopsy Journal Article


Authors: Damerla, R. R.; Lee, N. Y.; You, D.; Soni, R.; Shah, R.; Reyngold, M.; Katabi, N.; Wu, V.; McBride, S. M.; Tsai, C. J.; Riaz, N.; Powell, S. N.; Babady, N. E.; Viale, A.; Higginson, D. S.
Article Title: Detection of early human papillomavirus-associated cancers by liquid biopsy
Abstract: PURPOSE A circulating tumor DNA (ctDNA) test to detect plasma Epstein-Barr viral DNA can be used to screen for early nasopharyngeal cancers; however, the reported sensitivity of viral ctDNA tests to detect human papillomavirus (HPV)-associated cancers is modest. We assessed the utility of droplet digital polymerase chain reaction (dd PCR) to detect early-stage H PV-associated cancers using sequential H PV16 and HPV33 assays that account for HPV subtype distribution and subtype sequence variants. PATIENTS AND METHODS We collected plasma specimens from 97 HPV-positive patients with oropharyngeal squamous cell carcinoma and eight patients with HPV-positive anal squamous cell carcinoma, each with locoregionally confined disease. Negative controls included samples from seven patients with HPV-negative head and neck cancers and 20 individuals without cancer. RESULTS Of 97 patients with nonmetastatic, locoregionally confined oropharyngeal squamous cell carcinoma, 90 patients had detectable HPV16 ctDNA and three patients had HPV33 ctDNA, indicating an overall sensitivity of 95.6%. Seven of eight patients with early anal cancer were HPV16 ctDNA positive. No HPV ctDNA was detected in 27 negative controls, indicating 100% specificity. HPV16 ctDNA was detected in 19 of 19 patients with low-volume disease, defined as patients with a single, asymptomatic positive lymph node (N1) or an isolated T1-2 asymptomatic primary tumor. HPV16 ctDNA levels directly corresponded to tumor responses to chemoradiation and surgery. CONCLUSION With an updated understanding of HPV subtypes and sequence variation, HPV ctD NA by ddPCR is highly sensitive and specific, identifying HPV16 and HPV33 subtypes in a similar distribution as reported in major genomic profiling studies. The detection of small tumors indicates that HPV16 and HPV33 ctDNA ddPCR could be readily used in early detection screening trials and in disease response monitoring, analogous to Epstein-Barr virus DNA. (C) 2019 by American Society of Clinical Oncology
Keywords: survival; infection; radiotherapy; prevalence; dna; plasma; chemoradiotherapy; squamous-cell carcinoma; oropharyngeal carcinoma; locally advanced head
Journal Title: JCO Precision Oncology
Volume: 3
ISSN: 2473-4284
Publisher: American Society of Clinical Oncology  
Date Published: 2019-04-03
Language: English
ACCESSION: WOS:000493744000001
DOI: 10.1200/po.18.00276
PROVIDER: wos
PMCID: PMC6726127
PUBMED: 31485558
Notes: Article -- Source: Wos
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MSK Authors
  1. Simon Nicholas Powell
    189 Powell
  2. Ngolela Esther Babady
    73 Babady
  3. Nadeem Riaz
    251 Riaz
  4. Nancy Y. Lee
    604 Lee
  5. Nora Katabi
    197 Katabi
  6. Marsha Laufer
    32 Laufer
  7. Agnes Viale
    214 Viale
  8. Daoqi You
    26 You
  9. Sean Matthew McBride
    151 McBride
  10. Chiaojung Jillian   Tsai
    118 Tsai
  11. Rekha   Soni
    4 Soni
  12. Rachna Shah
    5 Shah
  13. Vanessa Joyce Wu
    3 Wu