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 (ddPCR) to detect early-stage HPV-associated cancers using sequential HPV16 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 ctDNA 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.
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 (ddPCR) to detect early-stage HPV-associated cancers using sequential HPV16 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 ctDNA 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.
Authors: K Kian Ang; Jonathan Harris; Richard Wheeler; Randal Weber; David I Rosenthal; Phuc Felix Nguyen-Tân; William H Westra; Christine H Chung; Richard C Jordan; Charles Lu; Harold Kim; Rita Axelrod; C Craig Silverman; Kevin P Redmond; Maura L Gillison Journal: N Engl J Med Date: 2010-06-07 Impact factor: 91.245
Authors: Hongbin Cao; Alice Banh; Shirley Kwok; Xiaoli Shi; Simon Wu; Trevor Krakow; Brian Khong; Brindha Bavan; Rajeev Bala; Benjamin A Pinsky; Dimitrios Colevas; Nader Pourmand; Albert C Koong; Christina S Kong; Quynh-Thu Le Journal: Int J Radiat Oncol Biol Phys Date: 2011-10-08 Impact factor: 7.038
Authors: Anil K Chaturvedi; Eric A Engels; Ruth M Pfeiffer; Brenda Y Hernandez; Weihong Xiao; Esther Kim; Bo Jiang; Marc T Goodman; Maria Sibug-Saber; Wendy Cozen; Lihua Liu; Charles F Lynch; Nicolas Wentzensen; Richard C Jordan; Sean Altekruse; William F Anderson; Philip S Rosenberg; Maura L Gillison Journal: J Clin Oncol Date: 2011-10-03 Impact factor: 44.544
Authors: Jeremy Setton; Nicola Caria; Jonathan Romanyshyn; Lawrence Koutcher; Suzanne L Wolden; Michael J Zelefsky; Nicholas Rowan; Eric J Sherman; Matthew G Fury; David G Pfister; Richard J Wong; Jatin P Shah; Dennis H Kraus; Weiji Shi; Zhigang Zhang; Karen D Schupak; Daphna Y Gelblum; Shyam D Rao; Nancy Y Lee Journal: Int J Radiat Oncol Biol Phys Date: 2010-12-16 Impact factor: 7.038
Authors: Eileen F Dunne; Elizabeth R Unger; Maya Sternberg; Geraldine McQuillan; David C Swan; Sonya S Patel; Lauri E Markowitz Journal: JAMA Date: 2007-02-28 Impact factor: 56.272
Authors: Sun M Ahn; Jason Y K Chan; Zhe Zhang; Hao Wang; Zubair Khan; Justin A Bishop; William Westra; Wayne M Koch; Joseph A Califano Journal: JAMA Otolaryngol Head Neck Surg Date: 2014-09 Impact factor: 6.223
Authors: Keiko Akagi; Jingfeng Li; Tatevik R Broutian; Hesed Padilla-Nash; Weihong Xiao; Bo Jiang; James W Rocco; Theodoros N Teknos; Bhavna Kumar; Danny Wangsa; Dandan He; Thomas Ried; David E Symer; Maura L Gillison Journal: Genome Res Date: 2013-11-07 Impact factor: 9.043
Authors: Giulia Siravegna; Connor J O'Boyle; Jeremy D Richmon; Daniel L Faden; Shohreh Varmeh; Natalia Queenan; Alexa Michel; Jarrod Stein; Julia Thierauf; Peter M Sadow; William C Faquin; Simon K Perry; Adam Z Bard; Wei Wang; Daniel G Deschler; Kevin S Emerick; Mark A Varvares; Jong C Park; John R Clark; Annie W Chan; Vanessa Carlota Andreu Arasa; Osamu Sakai; Jochen Lennerz; Ryan B Corcoran; Lori J Wirth; Derrick T Lin; A John Iafrate Journal: Clin Cancer Res Date: 2022-02-15 Impact factor: 13.801
Authors: Yue Cao; Catherine T Haring; Michelle Mierzwa; J Chad Brenner; Collin Brummel; Chandan Bhambhani; Madhava Aryal; Choonik Lee; Molly Heft Neal; Apurva Bhangale; Wenjin Gu; Keith Casper; Kelly Malloy; Yilun Sun; Andrew Shuman; Mark E Prince; Matthew E Spector; Steven Chinn; Jennifer Shah; Caitlin Schonewolf; Jonathan B McHugh; Ryan E Mills; Muneesh Tewari; Francis P Worden; Paul L Swiecicki Journal: Clin Cancer Res Date: 2021-10-26 Impact factor: 13.801
Authors: L Cabel; C Bonneau; A Bernard-Tessier; D Héquet; C Tran-Perennou; G Bataillon; R Rouzier; J-G Féron; V Fourchotte; J-F Le Brun; C Benoît; M Rodrigues; N Scher; M Minsat; M-E Legrier; I Bièche; C Proudhon; X Sastre-Garau; F-C Bidard; E Jeannot Journal: ESMO Open Date: 2021-05-19
Authors: Susanne Flach; Karen Howarth; Sophie Hackinger; Christodoulos Pipinikas; Pete Ellis; Kirsten McLay; Giovanni Marsico; Tim Forshew; Christoph Walz; Christoph A Reichel; Olivier Gires; Martin Canis; Philipp Baumeister Journal: Br J Cancer Date: 2022-02-07 Impact factor: 9.075
Authors: Catherine T Haring; Collin Brummel; Chandan Bhambhani; Brittany Jewell; Molly Heft Neal; Apurva Bhangale; Keith Casper; Kelly Malloy; Scott McLean; Andrew Shuman; Chaz Stucken; Andrew Rosko; Mark Prince; Carol Bradford; Avraham Eisbruch; Michelle Mierzwa; Muneesh Tewari; Francis P Worden; Paul L Swiecicki; Matthew E Spector; J Chad Brenner Journal: Oral Oncol Date: 2021-06-14 Impact factor: 5.337
Authors: Anna C Lefèvre; Niels Pallisgaard; Camilla Kronborg; Karen L Wind; Søren R P Krag; Karen-Lise G Spindler Journal: Cancers (Basel) Date: 2021-05-18 Impact factor: 6.639