The clinical utility of circulating human papillomavirus across squamous cell carcinomas

Authors

  • Karen-Lise G. Spindler Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  • Anne V. Jakobsen Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  • Jesper G. Eriksen Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  • Lars Fokdal Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Oncology, Vejle Hospital, Vejle, Denmark
  • Marianne Nordsmark Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  • Lise B. J. Thorsen Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  • Karen L. Wind Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  • Anna C. Lefevre Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
  • Jens Overgaard Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

DOI:

https://doi.org/10.2340/1651-226X.2025.41288

Keywords:

squamous cell carcinoma, circulating tumor DNA, Human papilloma virus

Abstract

Background and purpose: The similarities in biology, treatment regimens and outcome between the different human papillomavirus (HPV) associated squamous cell carcinomas (SCCs) allow for extrapolation of results generated from one SC tumor type to another.

In HPV associated cancers, HPV is integrated into the tumor genome and can consequently be detected in the circulating fragments of the tumor DNA. Thus, measurement of HPV in the plasma is a surrogate for circulating tumor DNA (ctDNA) and holds promise as a clinically relevant biomarker in HPV associated cancers.

With the present overview we aim to present the status of circulating HPV studies in SCCs, the clinical potential and the gaps of knowledge, with the overall aim to facilitate the next steps into clinically relevant prospective trials.

Material and methods: We reviewed the literature and presented the data for each tumor type as well as analyses of the clinical utility across the SCC.

Results and interpretation: A total of 41 studies were identified in cervical, head and neck and anal SCC and we discuss the common signals from the results across the different tumor sites. Our results not only confirm the strong clinical potential but also emphasize an urgent need to coordinate studies to allow for relevant sample sizes and statistical validations.

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References

De Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020;8:e180–190.

https://doi.org/10.1016/S2214-109X(19)30488-7 DOI: https://doi.org/10.1016/S2214-109X(19)30488-7

Baumann M, Krause M, Overgaard J, Debus J, Bentzen SM, Daartz J, et al. Radiation oncology in the era of precision medicine. Nat Rev Cancer. 2016;16:234–249.

https://doi.org/10.1038/nrc.2016.18 DOI: https://doi.org/10.1038/nrc.2016.18

Withers HR. The four R’s of radiotherapy. In: Lett JT, Adler H, editors. Advances in radiation biology. New York, NY: Academic Press; 1975. p. 241–247. DOI: https://doi.org/10.1016/B978-0-12-035405-4.50012-8

Pajonk F, Vlashi E, McBride WH. Radiation resistance of cancer stem cells: the 4 R’s of radiobiology revisited. Stem Cells. 2010;28:639–648.

https://doi.org/10.1002/stem.318 DOI: https://doi.org/10.1002/stem.318

Withers HR, Taylor JMG, Maciejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol. 1988;27:131–146.

https://doi.org/10.3109/02841868809090333 DOI: https://doi.org/10.3109/02841868809090333

Lacas B, Bourhis J, Overgaard J, Zhang Q, Grégoire V, Nankivell M, et al. Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis. Lancet Oncol. 2017;18:1221–1237.

https://doi.org/10.1016/S1470-2045(17)30458-8 DOI: https://doi.org/10.1016/S1470-2045(17)30458-8

Overgaard J. Hypoxic Radiosensitization: adored and ignored. J Clin Oncol. 2007;25:4066–4074.

https://doi.org/10.1200/JCO.2007.12.7878 DOI: https://doi.org/10.1200/JCO.2007.12.7878

Eriksen JG, Maare C, Johansen J, Primdahl H, Evensen J, Kristensen CA, et al. OC-0271: 5-Y update of the randomized phase III trial DA-HANCA19: primary (Chemo) RT +/- zalutumumab in HNSCC. Radiother Oncol. 2018;127:S137–S138.

https://doi.org/10.1016/s0167-8140(18)30581-4 DOI: https://doi.org/10.1016/S0167-8140(18)30581-4

Mehanna H, Robinson M, Hartley A, Kong A, Foran B, Fulton-Lieuw T, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet. 2019;393:51–60.

https://doi.org/10.1016/S0140-6736(18)32752-1 DOI: https://doi.org/10.1016/S0140-6736(18)32752-1

Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ, et al. Radiotherapy plus cetuximab or cisplatin in human papilloma-virus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019;393:40–50.

https://doi.org/10.1016/S0140-6736(18)32779-X DOI: https://doi.org/10.1016/S0140-6736(18)32779-X

Gebre-Medhin M, Brun E, Engström P, Haugen Cange H, Hammarstedt-Nordenvall L, Reizenstein J, et al. ARTSCAN III: a randomized phase III study comparing chemoradiotherapy with cisplatin versus cetuximab in patients with locoregionally advanced head and neck squamous cell cancer. J Clin Oncol. 2021;39:38–47. DOI: https://doi.org/10.1200/JCO.20.02072

https://doi.org/10.1200/JCO.20

Lee NY, Ferris RL, Psyrri A, Haddad RI, Tahara M, Bourhis J, et al. Avelumab plus standard-of-care chemoradiotherapy versus chemoradio-therapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, place-bo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2021;22(4):450–462.

https://doi.org/10.1016/S1470-2045(20)30737-3 DOI: https://doi.org/10.1016/S1470-2045(20)30737-3

Martin D, Balermpas P, Gollrad J, Weiß C, Valentini C, Stuschke M, et al. RADIANCE – radiochemotherapy with or without Durvalumab in the treatment of anal squamous cell carcinoma: a randomized multicenter phase II trial. Clin Transl Radiat Oncol. 2020;23:43–49.

https://doi.org/10.1016/j.ctro.2020.04.010 DOI: https://doi.org/10.1016/j.ctro.2020.04.010

Vendrely V, Ronchin P, Minsat M, Le Malicot K, Lemanski C, Mirabel X, et al. Panitumumab in combination with chemoradiotherapy for the treatment of locally-advanced anal canal carcinoma: results of the FFCD 0904 phase II trial. Radiother Oncol. 2023;186:109742.

https://doi.org/10.1016/j.radonc.2023.109742 DOI: https://doi.org/10.1016/j.radonc.2023.109742

Lassen P, Primdahl H, Johansen J, Kristensen CA, Andersen E, Andersen LJ, et al. Impact of HPV-associated p16-expression on radiotherapy outcome in advanced oropharynx and non-oropharynx cancer. Radiother Oncol. 2014;113:310–316.

https://doi.org/10.1016/j.radonc.2014.11.032 DOI: https://doi.org/10.1016/j.radonc.2014.11.032

Serup-Hansen E, Linnemann D, Skovrider-Ruminski W, Hgødall E, Geertsen PF, Havsteen H. Human papillomavirus genotyping and p16 expression as prognostic factors for patients with American Joint Committee on Cancer stages I to III carcinoma of the anal canal. J Clin Oncol. 2014;32:1812–1817.

https://doi.org/10.1200/JCO.2013.52.3464 DOI: https://doi.org/10.1200/JCO.2013.52.3464

Lilja-Fischer JK, Eriksen JG, Georgsen JB, Vo TT, Larsen SR, Cheng J, et al. Prognostic impact of PD-L1 in oropharyngeal cancer after primary curative radiotherapy and relation to HPV and tobacco smoking. Acta Oncol. 2020;59:666–672.

https://doi.org/10.1080/0284186X.2020.1729407 DOI: https://doi.org/10.1080/0284186X.2020.1729407

Mehanna H, Taberna M, von Buchwald C, Tous S, Brooks J, Mena M, et al. Prognostic implications of p16 and HPV discordance in oropha-ryngeal cancer (HNCIG-EPIC-OPC): a multicentre, multinational, individual patient data analysis. Lancet Oncol. 2023;24(3):239–251.

https://doi.org/10.1016/S1470-2045(23)00013-X DOI: https://doi.org/10.1016/S1470-2045(23)00013-X

Lefèvre AC, Pallisgaard N, Kronborg C, Wind KL, Krag SRP, Spindler KG. The clinical Alue of measuring circulating HPV DNA during chemo-radiotherapy in squamous cell carcinoma of the anus. Cancers (Basel). 2021;13(10):2451.

https://doi.org/10.3390/cancers13102451 DOI: https://doi.org/10.3390/cancers13102451

Gameiro SR, Strauss J, Gulley JL, Schlom J. Preclinical and clinical studies of bintrafusp alfa, a novel bifunctional anti-PD-L1/TGFβRII agent: Current status. Exp Biol Med. 2022;247(13):1124–1134.

https://doi.org/10.1177/15353702221089910 DOI: https://doi.org/10.1177/15353702221089910

Corcoran RB, Chabner BA. Application of cell-free DNA analysis to cancer treatment. N Engl J Med. 2018;379(18):1754–1765.

https://doi.org/10.1056/nejmra1706174 DOI: https://doi.org/10.1056/NEJMra1706174

Mauri G, Vitiello PP, Sogari A, Crisafulli G, Sartore-Bianchi A, Marsoni S, et al. Liquid biopsies to monitor and direct cancer treatment in colorectal cancer. Br J Cancer. 2022;127(3):394–407.

https://doi.org/10.1038/s41416-022-01769-8 DOI: https://doi.org/10.1038/s41416-022-01769-8

Boysen AK, Pallisgaard N, Andersen CSA, Spindler KLG. Circulating tumor DNA as a marker of minimal residual disease following local treatment of metastases from colorectal cancer. Acta Oncol. 2020;59:1424–1429.

https://doi.org/10.1080/0284186X.2020.1806357 DOI: https://doi.org/10.1080/0284186X.2020.1806357

Jeannot E, Becette V, Campitelli M, Calméjane MA, Lappartient E, Ruff E, et al. Circulating human papillomavirus DNA detected using droplet digital PCR in the serum of patients diagnosed with early stage human papillomavirus-associated invasive carcinoma. J Pathol Clin Res. 2016;2(4):201–209.

https://doi.org/10.1002/cjp2.47 DOI: https://doi.org/10.1002/cjp2.47

Cabel L, Jeannot E, Bieche I, Vacher S, Callens C, Bazire L, et al. Prognostic impact of residual HPV ctDNA detection after chemoradiotherapy for anal squamous cell carcinoma. Clin Cancer Res. 2018;24:5767–5771.

https://doi.org/10.1158/1078-0432.CCR-18-0922 DOI: https://doi.org/10.1158/1078-0432.CCR-18-0922

Bernard-Tessier A, Jeannot E, Guenat D, Debernardi A, Michel M, Proudhon C, et al. Clinical validity of HPV circulating tumor DNA in advanced anal carcinoma: an ancillary study to the EPITOPES-HPV02 trial. Clin Cancer Res. 2019;25:2109–2115.

https://doi.org/10.1158/1078-0432.CCR-18-2984 DOI: https://doi.org/10.1158/1078-0432.CCR-18-2984

Mazurek AM, Małusecka E, Jabłońska I, Vydra N, Rutkowski TW, Giglok M, et al. Circulating HPV16 DNA in blood plasma as prognosticator and early indicator of cancer recurrence in radio-chemotherapy for anal cancer. Cancers (Basel). 2023;15(3):867.

https://doi.org/10.3390/cancers15030867 DOI: https://doi.org/10.3390/cancers15030867

Tanaka H, Takemoto N, Horie M, Takai E, Fukusumi T, Suzuki M, et al. Circulating tumor HPV DNA complements PET-CT in guiding man-agement after radiotherapy in HPV-related squamous cell carcinoma of the head and neck. Int J Cancer. 2021;148:995–1005.

https://doi.org/10.1002/ijc.33287 DOI: https://doi.org/10.1002/ijc.33287

Lee JY, Garcia-Murillas I, Cutts RJ, De Castro DG, Grove L, Hurley T, et al. Predicting response to radical (chemo)radiotherapy with circu-lating HPV DNA in locally advanced head and neck squamous carcinoma. Br J Cancer. 2017;117:876–883.

https://doi.org/10.1038/bjc.2017.258 DOI: https://doi.org/10.1038/bjc.2017.258

Dahlstrom KR, Li G, Hussey CS, Vo JT, Wei Q, Zhao CS, et al. Erratum: circulating human papillomavirus DNA as a marker for disease extent and recurrence among patients with oropharyngeal cancer. Cancer. 2015;121(19):3455–3464. DOI: https://doi.org/10.1002/cncr.29538

https://doi.org/10.1002/cncr.29772 DOI: https://doi.org/10.1002/cncr.29772

Hanna GJ, Supplee JG, Kuang Y, Mahmood U, Lau CJ, Haddad RI, et al. Plasma HPV cell-free DNA monitoring in advanced HPV-associated oropharyngeal cancer. Ann Oncol. 2018;29:1980–1986.

https://doi.org/10.1093/annonc/mdy251 DOI: https://doi.org/10.1093/annonc/mdy251

Hanna GJ, Lau CJ, Mahmood U, Supplee JG, Mogili AR, Haddad RI, et al. Salivary HPV DNA informs locoregional disease status in advanced HPV-associated oropharyngeal cancer. Oral Oncol. 2019;95:120–126.

https://doi.org/10.1016/j.oraloncology.2019.06.019 DOI: https://doi.org/10.1016/j.oraloncology.2019.06.019

Chera BS, Kumar S, Beaty BT, Marron D, Jefferys S, Green R, 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.

https://doi.org/10.1158/1078-0432.CCR-19-0211 DOI: https://doi.org/10.1158/1078-0432.CCR-19-0211

Cao Y, Haring CT, Brummel C, Bhambhani C, Aryal M, Lee C, et al. Early HPV ctDNA kinetics and imaging biomarkers predict therapeutic response in p16+ oropharyngeal squamous cell carcinoma. Clin Cancer Res. 2022;28:350–359.

https://doi.org/10.1158/1078-0432.CCR-21-2338 DOI: https://doi.org/10.1158/1078-0432.CCR-21-2338

Adrian G, Forslund O, Pedersen L, Sjövall J, Gebre-Medhin M. Circulating tumour HPV16 DNA quantification – a prognostic tool for progres-sion-free survival in patients with HPV-related oropharyngeal carcinoma receiving curative chemoradiotherapy. Radiother Oncol. 2023;186:109773.

https://doi.org/10.1016/j.radonc.2023.109773 DOI: https://doi.org/10.1016/j.radonc.2023.109773

Califano J, Yousef A, Mostafa H, Valsamakis A, Zhang X, Batis N, et al. Lead time to recurrence after posttreatment plasma and saliva HPV DNA testing in patients with low-risk HPV oropharynx cancer. JAMA Otolaryngol Head Neck Surg. 2023;149(9):812–813.

https://doi.org/10.1001/jamaoto.2023.1730 DOI: https://doi.org/10.1001/jamaoto.2023.1730

Cao H, Banh A, Kwok S, Shi X, Wu S, Krakow T, et al. Quantitation of human papillomavirus DNA in plasma of oropharyngeal carcinoma patients. Int J Radiat Oncol Biol Phys. 2012;82:351–358.

https://doi.org/10.1016/j.ijrobp.2011.05.061 DOI: https://doi.org/10.1016/j.ijrobp.2011.05.061

Chera BS, Kumar S, Shen C, Amdur R, Dagan R, Green R, 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. DOI: https://doi.org/10.1200/JCO.19.02444

https://doi.org/10.1200/JCO.19

Kedzia H, Gozdzicka-Józefiak A, Wolna M, Tomczak E. Distribution of human papillomavirus 16 in the blood of women with uterine cervix carcinoma. Eur J Gynaecol Oncol. 1992;13(6):522–526.

Cabel L, Bonneau C, Bernard-Tessier A, Héquet D, Tran-Perennou C, Bataillon G, et al. HPV ctDNA detection of high-risk HPV types during chemoradiotherapy for locally advanced cervical cancer. ESMO Open. 2021;6:100154.

https://doi.org/10.1016/j.esmoop.2021.100154 DOI: https://doi.org/10.1016/j.esmoop.2021.100154

Pornthanakasem W, Shotelersuk K, Termrungruanglert W, Voravud N, Niruthisard S, Mutirangura A. Human papillomavirus DNA in plasma of patients with cervical cancer. BMC Cancer. 2001;1:2.

https://doi.org/10.1186/1471-2407-1-2 DOI: https://doi.org/10.1186/1471-2407-1-2

Cheung TH, Yim SF, Yu MY, Worley MJ, Fiascone SJ, Chiu RWK, et al. Liquid biopsy of HPV DNA in cervical cancer. J Clin Virol 2019;114:32–36.

https://doi.org/10.1016/j.jcv.2019.03.005 DOI: https://doi.org/10.1016/j.jcv.2019.03.005

Jeannot E, Latouche A, Bonneau C, Calmejane MA, Beaufort C, Ruigrok-Ritstier K, et al. Circulating HPV DNA as a marker for early detection of relapse in patients with cervical cancer. Clin Cancer Res. 2021;27:5869–5877.

https://doi.org/10.1158/1078-0432.CCR-21-0625 DOI: https://doi.org/10.1158/1078-0432.CCR-21-0625

Campitelli M, Jeannot E, Peter M, Lappartient E, Saada S, De la Rochefordière A, et al. Human papillomavirus mutational insertion: specific marker of circulating tumor DNA in cervical cancer patients. PLoS One. 2012;7(8):e43393.

https://doi.org/10.1371/journal.pone.0043393 DOI: https://doi.org/10.1371/journal.pone.0043393

Parameshwaran K, Sharma P, Rajendra S, Stelzer-Braid S, Xuan W, Rawlinson WD. Circulating human papillomavirus DNA detection in Barrett’s dysplasia and esophageal adenocarcinoma. Dis Esophagus. 2019;32(12):doz064.

https://doi.org/10.1093/dote/doz064 DOI: https://doi.org/10.1093/dote/doz064

Conesa-Zamora P, Doménech-Peris A, Orantes-Casado FJ, Ortiz-Reina S, Sahuquillo-Frías L, Acosta-Ortega J, et al. Effect of human papillo-mavirus on cell cycle-related proteins p16, Ki-67, Cyclin D1, p53, and ProEx C in precursor lesions of cervical carcinoma: a tissue mi-croarray study. Am J Clin Pathol. 2009;132(3):378–390.

https://doi.org/10.1309/AJCPO0WY1VIFCYDC DOI: https://doi.org/10.1309/AJCPO0WY1VIFCYDC

Liu VWS, Tsang P, Yip A, Ng TY, Wong LC, Ngan HYS. Low incidence of HPV DNA in sera of pretreatment cervical cancer patients. Gynecol Oncol. 2001;82:269–272.

https://doi.org/10.1006/gyno.2001.6289 DOI: https://doi.org/10.1006/gyno.2001.6289

Dong SM, Pai SI, Rha SH, Hildesheim A, Kurman RJ, Schwartz PE, et al. Detection and quantitation of human papillomavirus DNA in the plasma of patients with cervical carcinoma. Cancer Epidemiol Biomarkers Prev. 2002;11(1):3–6.

Sathish N, Abraham P, Peedicayil A, Sridharan G, John S, Shaji RV, et al. HPV DNA in plasma of patients with cervical carcinoma. J Clin Virol. 2004;31:204–209.

https://doi.org/10.1016/j.jcv.2004.03.013 DOI: https://doi.org/10.1016/j.jcv.2004.03.013

Kay P, Allan B, Denny L, Hoffman M, Williamson AL. Detection of HPV 16 and HPV 18 DNA in the blood of patients with cervical cancer. J Med Virol. 2005;75:435–439.

https://doi.org/10.1002/jmv.20294 DOI: https://doi.org/10.1002/jmv.20294

Shimada T, Yamaguchi N, Nishida N, Yamasaki K, Miura K, Katamine S, et al. Human papillomavirus DNA in plasma of patients with HPV16 DNA-positive uterine cervical cancer. Jpn J Clin Oncol. 2010;40:420–424.

https://doi.org/10.1093/jjco/hyp193 DOI: https://doi.org/10.1093/jjco/hyp193

Kang Z, Stevanovic S, Hinrichs CS, Cao L. Circulating cell-free DNA for metastatic cervical cancer detection, genotyping, and monitoring. Clin Cancer Res. 2017;23:6856–6862.

https://doi.org/10.1158/1078-0432.CCR-17-1553 DOI: https://doi.org/10.1158/1078-0432.CCR-17-1553

Bønløkke S, Stougaard M, Sorensen BS, Booth BB, Høgdall E, Nyvang GB, et al. The diagnostic value of circulating cell-free HPV DNA in plasma from cervical cancer patients. Cells. 2022;11(14):2170.

https://doi.org/10.3390/cells11142170 DOI: https://doi.org/10.3390/cells11142170

Ahn SM, Chan JYK, Zhang Z, Wang H, Khan Z, Bishop JA, et al. Saliva and plasma quantitative polymerase chain reaction-based detection and surveillance of human papillomavirus-related head and neck cancer. JAMA Otolaryngol Head Neck Surg. 2014;140:846–854.

https://doi.org/10.1001/jamaoto.2014.1338 DOI: https://doi.org/10.1001/jamaoto.2014.1338

Wang Y, Springer S, Mulvey CL, Silliman N, Schaefer J, Sausen M, 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. 201;7(293):293ra104.

https://doi.org/10.1126/scitranslmed.aaa8507 DOI: https://doi.org/10.1126/scitranslmed.aaa8507

Mazurek AM, Rutkowski T, Fiszer-Kierzkowska A, Małusecka E, Składowski K. Assessment of the total cfDNA and HPV16/18 detection in plasma samples of head and neck squamous cell carcinoma patients. Oral Oncol. 2016;54:36–41.

https://doi.org/10.1016/j.oraloncology.2015.12.002 DOI: https://doi.org/10.1016/j.oraloncology.2015.12.002

Rutkowski TW, Mazurek AM, Śnietura M, Hejduk B, Jędrzejewska M, Bobek-Billewicz B, et al. Circulating HPV16 DNA may complement imaging assessment of early treatment efficacy in patients with HPV-positive oropharyngeal cancer. J Transl Med. 2020;18(1):167.

https://doi.org/10.1186/s12967-020-02330-y DOI: https://doi.org/10.1186/s12967-020-02330-y

Reder H, Taferner VF, Wittekindt C, Bräuninger A, Speel EJM, Gattenlöhner S, et al. Plasma cell-free human papillomavirus oncogene E6 and E7 DNA predicts outcome in oropharyngeal squamous cell carcinoma. J Mol Diagn. 2020;22:1333–1343.

https://doi.org/10.1016/j.jmoldx.2020.08.002 DOI: https://doi.org/10.1016/j.jmoldx.2020.08.002

Haring CT, Bhambhani C, Brummel C, Jewell B, Bellile E, Heft Neal ME, et al. Human papilloma virus circulating tumor DNA assay predicts treatment response in recurrent/metastatic head and neck squamous cell carcinoma. Oncotarget. 2021;12(13):1214–1229.

https://doi.org/10.18632/oncotarget.27992 DOI: https://doi.org/10.18632/oncotarget.27992

Siravegna G, O’Boyle CJ, Varmeh S, Queenan N, Michel A, Stein J, et al. Cell-free HPV DNA provides an accurate and rapid diagnosis of HPV-associated head and neck cancer. Clin Cancer Res. 2022;28(4):719–727.

https://doi.org/10.1158/1078-0432.CCR-21-3151 DOI: https://doi.org/10.1158/1078-0432.CCR-21-3151

Tanaka H, Suzuki M, Takemoto N, Fukusumi T, Eguchi H, Takai E, et al. Performance of oral HPV DNA, oral HPV mRNA and circulating tumor HPV DNA in the detection of HPV-related oropharyngeal cancer and cancer of unknown primary. Int J Cancer. 2022;150:174–186.

https://doi.org/10.1002/ijc.33798 DOI: https://doi.org/10.1002/ijc.33798

Routman DM, Kumar S, Chera BS, Jethwa KR, Van Abel KM, Frechette K, et al. Detectable postoperative circulating tumor human papillo-mavirus DNA and association with recurrence in patients with HPV-associated oropharyngeal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2022;113:530–538.

https://doi.org/10.1016/j.ijrobp.2022.02.012 DOI: https://doi.org/10.1016/j.ijrobp.2022.02.012

Cabel L, Bidard FC, Servois V, Cacheux W, Mariani P, Romano E, et al. HPV circulating tumor DNA to monitor the efficacy of anti-PD-1 thera-py in metastatic squamous cell carcinoma of the anal canal: a case report. Int J Cancer. 2017;141:1667–1670.

https://doi.org/10.1002/ijc.30863 DOI: https://doi.org/10.1002/ijc.30863

Veyer D, Pavie J, Pernot S, Mandavit M, Garrigou S, Lucas M-L, et al. HPV-circulating tumoural DNA by droplet-based digital polymerase chain reaction, a new molecular tool for early detection of HPV metastatic anal cancer? A case report. Eur J Cancer. 2019;112:34–37.

https://doi.org/10.1016/j.ejca.2019.02.012 DOI: https://doi.org/10.1016/j.ejca.2019.02.012

Lee JY, Cutts RJ, White I, Augustin Y, Garcia-Murillas I, Fenwick K, et al. Next generation sequencing assay for detection of circulating HPV DNA (cHPV-DNA) in patients undergoing radical (chemo)radiotherapy in anal squamous cell carcinoma (ASCC). Front Oncol. 2020;10:505.

https://doi.org/10.3389/fonc.2020.00505 DOI: https://doi.org/10.3389/fonc.2020.00505

Damerla RR, Lee NY, You D, Soni R, Shah R, Reyngold M, et al. Detection of early human papillomavirus-associated cancers by liquid biopsy. JCO Precis Oncol. 2019;3:PO.18.00276.

https://doi.org/10.1200/PO.18.00276 DOI: https://doi.org/10.1200/PO.18.00276

Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde 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(346):346ra92.

https://doi.org/10.1126/scitranslmed.aaf6219 DOI: https://doi.org/10.1126/scitranslmed.aaf6219

Callesen LB, Hamfjord J, Boysen AK, Pallisgaard N, Guren TK, Kure EH, et al. Circulating tumour DNA and its clinical utility in predicting treatment response or survival in patients with metastatic colorectal cancer: a systematic review and meta-analysis. Br J Cancer. 2022;127:500–513.

https://doi.org/10.1038/s41416-022-01816-4 DOI: https://doi.org/10.1038/s41416-022-01816-4

Spindler KG. Methodological, biological and clinical aspects of circulating free DNA in metastatic colorectal cancer. Acta Oncol. 2017;56:7–16.

https://doi.org/10.1080/0284186X.2016.1253861 DOI: https://doi.org/10.1080/0284186X.2016.1253861

Jakobsen A, Andersen RF, Hansen TF, Jensen LH, Faaborg L, Steffensen KD, et al. Early ctDNA response to chemotherapy. A potential surrogate marker for overall survival. Eur J Cancer. 2021;149:128–133.

https://doi.org/10.1016/j.ejca.2021.03.006 DOI: https://doi.org/10.1016/j.ejca.2021.03.006

Reinert T, Schøler LV, Thomsen R, Tobiasen H, Vang S, Nordentoft I, et al. Analysis of circulating tumour DNA to monitor disease burden following colorectal cancer surgery. Gut. 2016;65:625–634.

https://doi.org/10.1136/gutjnl-2014-308859 DOI: https://doi.org/10.1136/gutjnl-2014-308859

Bønløkke S, Steiniche T, Sorensen BS, Nyvang GB, Lindegaard JC, Blaakær J, et al. Circulating cell-free HPV DNA is a strong marker for disease severity in cervical cancer. Mol Oncol. 2024;18(5):1231–1244.

https://doi.org/10.1002/1878-0261.13538 DOI: https://doi.org/10.1002/1878-0261.13538

Additional Files

Published

2025-01-02

How to Cite

Spindler, K.-L. G., Jakobsen, A. V., Eriksen, J. G., Fokdal, L., Nordsmark, M., Thorsen, L. B. J., … Overgaard, J. (2025). The clinical utility of circulating human papillomavirus across squamous cell carcinomas. Acta Oncologica, 64, 1–12. https://doi.org/10.2340/1651-226X.2025.41288