Circulating tumor HPV DNA complements PET-CT in guiding management after radiotherapy in HPV-related squamous cell carcinoma of the head and neck

Hidenori Tanaka, Norihiko Takemoto, Masafumi Horie, Erina Takai, Takahito Fukusumi, Motoyuki Suzuki, Hirotaka Eguchi, Sho Komukai, Mitsuaki Tatsumi, Fumiaki Isohashi, Kazuhiko Ogawa, Shinichi Yachida, Hidenori Inohara, Hidenori Tanaka, Norihiko Takemoto, Masafumi Horie, Erina Takai, Takahito Fukusumi, Motoyuki Suzuki, Hirotaka Eguchi, Sho Komukai, Mitsuaki Tatsumi, Fumiaki Isohashi, Kazuhiko Ogawa, Shinichi Yachida, Hidenori Inohara

Abstract

Positron emission tomography and computed tomography (PET-CT) is widely used to assess the response to radiotherapy. However, the ability of PET-CT to predict treatment failure in human papillomavirus (HPV)-related squamous cell carcinoma of the head and neck (HNSCC) is unsatisfactory. We quantified circulating tumor HPV type16 DNA (ctHPV16DNA) using optimized droplet digital PCR in 35 patients with HPV16-related HNSCC, who received radiotherapy with or without chemotherapy, and prospectively correlated ctHPV16DNA and metabolic response with treatment failure. After a median follow-up of 21 months, ctHPV16DNA and PET-CT had similar negative predictive values (89.7% vs 84.0%), whereas the positive predictive value was much higher in ctHPV16DNA than in PET-CT (100% vs 50.0%). Notably, six patients who had detectable posttreatment ctHPV16DNA all had treatment failure irrespective of metabolic response, whereas none of five patients who had partial metabolic response without detectable posttreatment ctHPV16DNA had treatment failure. The risk of treatment failure was high in patients who had incomplete metabolic response with detectable posttreatment ctHPV16DNA (hazard ratio [HR], 138.8; 95% confidence interval [CI], 15.5-3366.4; P < .0001) and intermediate in patients who had discordant results between metabolic response and posttreatment ctHPV16DNA (HR, 4.7; 95% CI, 0.8-36.2, P = .09) as compared with patients who had complete metabolic response without detectable posttreatment ctHPV16DNA. One-year event-free survival rates of each risk group were 0%, 88% (95% CI, 46-98) and 95% (95% CI, 72-99), respectively (P < .0001). In conclusion, posttreatment ctHPV16DNA complements PET-CT and helps guide decisions managing patients with HPV16-related HNSCC after radiotherapy.

Keywords: circulating tumor DNA; droplet digital PCR; human papillomavirus; positron emission tomography and computed tomography; squamous cell carcinoma of the head and neck.

© 2020 Union for International Cancer Control.

References

REFERENCES

    1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359-E386.
    1. Mourad M, Jetmore T, Jategaonkar AA, Moubayed S, Moshier E, Urken ML. Epidemiological trends of head and neck cancer in the United States: a SEER population study. J Oral Maxillofac Surg. 2017;75:2562-2572.
    1. Fitzmaurice C, Allen C, Barber RM, et al. Global, regional, and National Cancer Incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol. 2017;3:524-548.
    1. Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92:709-720.
    1. D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356:1944-1956.
    1. Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14:467-475.
    1. Chaturvedi AK, Anderson WF, Lortet-Tieulent J, et al. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 2013;31:4550-4559.
    1. Machtay M, Moughan J, Trotti A, et al. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol. 2008;26:3582-3589.
    1. Mehanna H, Wong WL, McConkey CC, et al. PET-CT surveillance versus neck dissection in advanced head and neck cancer. N Engl J Med. 2016;374:1444-1454.
    1. Vainshtein JM, Spector ME, Stenmark MH, et al. Reliability of post-chemoradiotherapy F-18-FDG PET/CT for prediction of locoregional failure in human papillomavirus-associated oropharyngeal cancer. Oral Oncol. 2014;50:234-239.
    1. Rulach R, Zhou S, Hendry F, et al. 12 week PET-CT has low positive predictive value for nodal residual disease in human papillomavirus-positive oropharyngeal cancers. Oral Oncol. 2019;97:76-81.
    1. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24-35.
    1. Kim SA, Roh JL, Kim JS, et al. (18)F-FDG PET/CT surveillance for the detection of recurrence in patients with head and neck cancer. Eur J Cancer. 2017;72:62-70.
    1. Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol. 2013;10:472-484.
    1. Garcia-Murillas I, Schiavon G, Weigelt B, et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015;7:302ra133.
    1. Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M, Kosmider S, Skinner I, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci. Transl. Med. 2016;8:346ra92.
    1. Chaudhuri AA, Chabon JJ, Lovejoy AF, et al. Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling. Cancer Discov. 2017;7:1394-1403.
    1. Chabon JJ, Simmons AD, Lovejoy AF, et al. Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients. Nat Commun. 2016;7:11815.
    1. Chan KCA, Woo JKS, King A, et al. Analysis of plasma Epstein-Barr virus DNA to screen for nasopharyngeal cancer. N Engl J Med. 2017;377:513-522.
    1. Cao H, Banh A, Kwok S, et al. Quantitation of human papillomavirus DNA in plasma of oropharyngeal carcinoma patients. Int J Radiat Oncol Biol Phys. 2012;82:e351-e358.
    1. Chera BS, Kumar S, Beaty BT, et al. Rapid clearance profile of plasma circulating tumor HPV type 16 DNA during chemoradiotherapy correlates with disease control in HPV-associated oropharyngeal cancer. Clin Cancer Res. 2019;25:4682-4690.
    1. Damerla RR, Lee NY, You D, et al. Detection of early human papillomavirus-associated cancers by liquid biopsy. JCO Precis Oncol. 2019;3:1-17.
    1. Veyer D, Wack M, Mandavit M, et al. HPV circulating tumoral DNA quantification by droplet-based digital PCR: a promising predictive and prognostic biomarker for HPV-associated oropharyngeal cancers. Int J Cancer. 2019;147:1222-1227.
    1. Hanna GJ, Supplee JG, Kuang Y, et al. Plasma HPV cell-free DNA monitoring in advanced HPV-associated oropharyngeal cancer. Ann Oncol. 2018;29:1980-1986.
    1. Chera BS, Kumar S, Shen C, et al. Plasma circulating tumor HPV DNA for the surveillance of cancer recurrence in HPV-associated oropharyngeal cancer. J Clin Oncol. 2020;38:1050-1058.
    1. Fuessel Haws AL, He Q, Rady PL, et al. Nested PCR with the PGMY09/11 and GP5(+)/6(+) primer sets improves detection of HPV DNA in cervical samples. J Virol Methods. 2004;122:87-93.
    1. Chang JT, Kuo TF, Chen YJ, et al. Highly potent and specific siRNAs against E6 or E7 genes of HPV16- or HPV18-infected cervical cancers. Cancer Gene Ther. 2010;17:827-836.
    1. Huang SH, O'Sullivan B, Xu W, et al. Temporal nodal regression and regional control after primary radiation therapy for N2-N3 head-and-neck cancer stratified by HPV status. Int J Radiat Oncol Biol Phys. 2013;87:1078-1085.
    1. Partlová S, Bouček J, Kloudová K, et al. Distinct patterns of intratumoral immune cell infiltrates in patients with HPV-associated compared to non-virally induced head and neck squamous cell carcinoma. Onco Targets Ther. 2015;4:e965570.
    1. Liu HY, Milne R, Lock G, et al. Utility of a repeat PET/CT scan in HPV-associated oropharyngeal cancer following incomplete nodal response from (chemo)radiotherapy. Oral Oncol. 2019;88:153-159.
    1. Hong AM, Ferguson P, Dodds T, et al. Significant association of PD-L1 expression with human papillomavirus positivity and its prognostic impact in oropharyngeal cancer. Oral Oncol. 2019;92:33-39.
    1. Wang Y, Springer S, Mulvey CL, et al. Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Sci Transl Med. 2015;7:293ra104.
    1. Fakhry C, Blackford AL, Neuner G, et al. Association of oral human papillomavirus DNA persistence with cancer progression after primary treatment for oral cavity and oropharyngeal squamous cell carcinoma. JAMA Oncol. 2019;5:985-992.
    1. Lee JY, Garcia-Murillas I, Cutts RJ, et al. Predicting response to radical (chemo)radiotherapy with circulating HPV DNA in locally advanced head and neck squamous carcinoma. Br J Cancer. 2017;117:876-883.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅