Human Papillomavirus and Squamous Cell Carcinoma of Unknown Primary in the Head and Neck Region: A Comprehensive Review on Clinical Implications

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2021 Aug 10

PMID 34372502

Citations 7

Authors

Mikkel Hjordt Holm Larsen

Hani Ibrahim Channir

Christian von Buchwald

Affiliations

Soon will be listed here.

Abstract

Squamous cell carcinoma of unknown primary (SCCUP) is a challenging diagnostic subgroup of oropharyngeal squamous cell carcinoma (OPSCC). The incidence of SCCUP is increasing in parallel with the well-documented increase in OPSCC and is likewise driven by the increase in human papillomavirus (HPV). The SCCUP patient often presents with a cystic lymph node metastasis and undergoes an aggressive diagnostic and treatment program. Detection of HPV in cytologic specimens indicates an oropharyngeal primary tumor origin and can guide the further diagnostic strategy. Advances in diagnostic modalities, e.g., transoral robotic surgery and transoral laser microsurgery, have increased the successful identification of the primary tumor site in HPV-induced SCCUP, and this harbors a potential for de-escalation treatment and increased survival. This review provides an overview of HPV-induced SCCUP, diagnostic modalities, and treatment options.

Citing Articles

Decoding the Enigma: Harnessing HPV Testing for the Precision Care in Carcinoma Unknown Primary with Secondary Metastasis to the Neck in North Indian Population Undergoing TORS for Primary Identification.

Chettuvatti K, Panda N, Mittal A, Bakshi J, Das A Indian J Otolaryngol Head Neck Surg. 2024; 76(4):3133-3139.

PMID: 39130254 PMC: 11306854. DOI: 10.1007/s12070-024-04628-5.

Head and neck squamous cell carcinomas of unknown primary: Can ancillary studies help identify more primary tumor sites?.

Hutchens T, Thorstad W, Wang X, Li Y, Duncavage E, Sun L Exp Mol Pathol. 2024; 138:104915.

PMID: 38964052 PMC: 11458069. DOI: 10.1016/j.yexmp.2024.104915.

Comparison of Transoral and Transcervical Ultrasonography with MRI for the Diagnostic Work-Up of Oropharynx Tumors: A Protocol for a Multicenter Clinical Trial (SPOTUS).

Garset-Zamani M, Hvilsom G, Kjaergaard T, Plaschke C, Hahn C, Kaltoft M Diagnostics (Basel). 2024; 14(6).

PMID: 38534997 PMC: 10968743. DOI: 10.3390/diagnostics14060577.

Diagnostic Delay in HPV-Related Oropharyngeal Squamous Cell Carcinoma.

McGarey Jr P, Hamdi O, Donaldson L, Zhan K, Crandley E, Wilson D Int Arch Otorhinolaryngol. 2024; 28(1):e42-e49.

PMID: 38322446 PMC: 10843923. DOI: 10.1055/s-0043-1767795.

Step Serial Sectioning in Head and Neck Squamous Cell Carcinoma of Unknown Primary.

Hardman J, Harrington K, OLeary B, Robinson M, Paleri V JAMA Otolaryngol Head Neck Surg. 2023; 150(2):118-126.

PMID: 38127339 PMC: 10853833. DOI: 10.1001/jamaoto.2023.3993.

References

Karni R, Rich J, Sinha P, Haughey B . Transoral laser microsurgery: a new approach for unknown primaries of the head and neck. Laryngoscope. 2011; 121(6):1194-201. DOI: 10.1002/lary.21743. View

Herruer J, Taylor S, MacKay C, Ubayasiri K, Lammers D, Kuta V . Intraoperative Primary Tumor Identification and Margin Assessment in Head and Neck Unknown Primary Tumors. Otolaryngol Head Neck Surg. 2020; 162(3):313-318. DOI: 10.1177/0194599819900794. View

Chernock R, Lewis J . Approach to metastatic carcinoma of unknown primary in the head and neck: squamous cell carcinoma and beyond. Head Neck Pathol. 2015; 9(1):6-15. PMC: 4382479. DOI: 10.1007/s12105-015-0616-2. View

Sinha P, Lewis Jr J, Piccirillo J, Kallogjeri D, Haughey B . Extracapsular spread and adjuvant therapy in human papillomavirus-related, p16-positive oropharyngeal carcinoma. Cancer. 2011; 118(14):3519-30. DOI: 10.1002/cncr.26671. View

Begum S, Cao D, Gillison M, Zahurak M, Westra W . Tissue distribution of human papillomavirus 16 DNA integration in patients with tonsillar carcinoma. Clin Cancer Res. 2005; 11(16):5694-9. DOI: 10.1158/1078-0432.CCR-05-0587. View

Roets E, Tukanova K, Govarts A, Specenier P . Quality of life in oropharyngeal cancer: a structured review of the literature. Support Care Cancer. 2018; 26(8):2511-2518. DOI: 10.1007/s00520-018-4227-9. View

No J, Sung M, Hah J, Choi S, Lee M, Kim H . Prevalence and prognostic value of human papillomavirus genotypes in tonsillar squamous cell carcinoma: a Korean multicenter study. Cancer. 2014; 121(4):535-44. DOI: 10.1002/cncr.29086. View

Zhu L, Wang N . 18F-fluorodeoxyglucose positron emission tomography-computed tomography as a diagnostic tool in patients with cervical nodal metastases of unknown primary site: a meta-analysis. Surg Oncol. 2013; 22(3):190-4. DOI: 10.1016/j.suronc.2013.06.002. View

Axelsson L, Nyman J, Haugen-Cange H, Bove M, Johansson L, De Lara S . Prognostic factors for head and neck cancer of unknown primary including the impact of human papilloma virus infection. J Otolaryngol Head Neck Surg. 2017; 46(1):45. PMC: 5466757. DOI: 10.1186/s40463-017-0223-1. View

10.

Maxwell J, Ferris R, Gooding W, Cunningham D, Mehta V, Kim S . Extracapsular spread in head and neck carcinoma: impact of site and human papillomavirus status. Cancer. 2013; 119(18):3302-8. DOI: 10.1002/cncr.28169. View

11.

Grewal A, Rajasekaran K, Cannady S, Chalian A, Ghiam A, Lin A . Pharyngeal-sparing radiation for head and neck carcinoma of unknown primary following TORS assisted work-up. Laryngoscope. 2019; 130(3):691-697. DOI: 10.1002/lary.28200. View

12.

Phillips D . Smoking-related DNA and protein adducts in human tissues. Carcinogenesis. 2003; 23(12):1979-2004. DOI: 10.1093/carcin/23.12.1979. View

13.

Topf M, Vo A, Tassone P, Shumrick C, Luginbuhl A, Cognetti D . Unplanned readmission following transoral robotic surgery. Oral Oncol. 2017; 75:127-132. DOI: 10.1016/j.oraloncology.2017.11.009. View

14.

Cantrell S, Peck B, Li G, Wei Q, Sturgis E, Ginsberg L . Differences in imaging characteristics of HPV-positive and HPV-Negative oropharyngeal cancers: a blinded matched-pair analysis. AJNR Am J Neuroradiol. 2013; 34(10):2005-9. PMC: 3951375. DOI: 10.3174/ajnr.A3524. View

15.

Daneshpajouhnejad P, Miller J, Maleki Z . Diagnostic utility of high-risk human papillomavirus mRNA in situ hybridisation in squamous cell carcinoma of unknown primary in the head and neck and implementing American Society of Clinical Oncology guideline recommendations. Cytopathology. 2020; 31(6):547-554. DOI: 10.1111/cyt.12896. View

16.

Lydiatt W, Patel S, OSullivan B, Brandwein M, Ridge J, Migliacci J . Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017; 67(2):122-137. DOI: 10.3322/caac.21389. View

17.

Eytan D, Blackford A, Eisele D, Fakhry C . Prevalence of comorbidities and effect on survival in survivors of human papillomavirus-related and human papillomavirus-unrelated head and neck cancer in the United States. Cancer. 2018; 125(2):249-260. DOI: 10.1002/cncr.31800. View

18.

Cao D, Begum S, Ali S, Westra W . Expression of p16 in benign and malignant cystic squamous lesions of the neck. Hum Pathol. 2009; 41(4):535-9. DOI: 10.1016/j.humpath.2009.09.006. View

19.

Lee M, Fowler N, Adelstein D, Koyfman S, Prendes B, Burkey B . Detection and Oncologic Outcomes of Head and Neck Squamous Cell Carcinoma of Unknown Primary Origin. Anticancer Res. 2020; 40(8):4207-4214. DOI: 10.21873/anticanres.14421. View

20.

Mehta V, Johnson P, Tassler A, Kim S, Ferris R, Nance M . A new paradigm for the diagnosis and management of unknown primary tumors of the head and neck: a role for transoral robotic surgery. Laryngoscope. 2012; 123(1):146-51. DOI: 10.1002/lary.23562. View