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Erschienen in: European Archives of Oto-Rhino-Laryngology 6/2022

24.10.2021 | Head and Neck

Human papillomavirus testing in metastatic squamous cell carcinoma of the neck with unknown primary using PCR on fine-needle aspiration smears: a prospective clinical study

verfasst von: Hani Ibrahim Channir, Anne Fog Lomholt, Thomas Alexander Gerds, Birgitte Wittenborg Charabi, Katalin Kiss, Christian von Buchwald

Erschienen in: European Archives of Oto-Rhino-Laryngology | Ausgabe 6/2022

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Abstract

Purpose

Squamous cell carcinoma metastasis of the head and neck with unknown primary tumor (CUP) comprises a diagnostic challenge. Human papillomavirus (HPV) testing on cytologic specimens is gaining increasing focus as this may facilitate an early diagnosis of HPV-induced oropharyngeal carcinoma. This study aimed to prospectively assess PCR-based HPV-DNA testing on FNA smears in a clinical setting.

Methods

Patients referred to a tertiary Head and Neck Cancer Center with suspected CUP were included from November 2016 to November 2018. Scraped cell material from FNA smears was analyzed for HPV-DNA with PCR using general primers (GP5 + /GP6 +) and correlated with the origin and histology of the primary tumor (oropharynx vs. outside oropharynx or benign tumor). The turn-around time reflecting the workflow for HPV-DNA testing by PCR was also calculated.

Results

A total of 93 patients were enrolled in the study. The sensitivity and specificity were 86.7% [95% CI 75.4–94.1%] and 92.0% [95% CI 74.0–99.0%], and the positive and negative predictive values were 96.3% [95% CI 87.3–99.0%] and 74.2% [95% CI 59.9–84.7%], respectively. The turn-around time for HPV testing was a mean four calendar days.

Conclusion

HPV-DNA testing on FNA smears can be performed within a reasonable timeframe and can guide for the detection of an HPV-positive oropharyngeal primary tumor in the clinical setting for patients presenting with CUP of the head and neck.
Literatur
1.
Zurück zum Zitat Schroeder L, Boscolo-Rizzo P, Dal Cin E, Romeo S, Baboci L, Dyckhoff G et al (2017) Human papillomavirus as prognostic marker with rising prevalence in neck squamous cell carcinoma of unknown primary: a retrospective multicentre study. Eur J Cancer 74:73–81CrossRef Schroeder L, Boscolo-Rizzo P, Dal Cin E, Romeo S, Baboci L, Dyckhoff G et al (2017) Human papillomavirus as prognostic marker with rising prevalence in neck squamous cell carcinoma of unknown primary: a retrospective multicentre study. Eur J Cancer 74:73–81CrossRef
2.
Zurück zum Zitat Boscolo-Rizzo P, Schroeder L, Romeo S, Pawlita M (2015) The prevalence of human papillomavirus in squamous cell carcinoma of unknown primary site metastatic to neck lymph nodes: a systematic review. Clin Exp Metastasis 32:835–845CrossRef Boscolo-Rizzo P, Schroeder L, Romeo S, Pawlita M (2015) The prevalence of human papillomavirus in squamous cell carcinoma of unknown primary site metastatic to neck lymph nodes: a systematic review. Clin Exp Metastasis 32:835–845CrossRef
3.
Zurück zum Zitat Zamani M, Grønhøj C, Jensen DH, Carlander AF, Agander T, Kiss K et al (2020) The current epidemic of HPV-associated oropharyngeal cancer: an 18-year Danish population-based study with 2169 patients. Eur J Cancer 134:52–59CrossRef Zamani M, Grønhøj C, Jensen DH, Carlander AF, Agander T, Kiss K et al (2020) The current epidemic of HPV-associated oropharyngeal cancer: an 18-year Danish population-based study with 2169 patients. Eur J Cancer 134:52–59CrossRef
4.
Zurück zum Zitat Bernadt CT, Collins BT (2017) Fine-needle aspiration biopsy of HPV-related squamous cell carcinoma of the head and neck: current ancillary testing methods for determining HPV status. Diagn Cytopathol 45:221–229CrossRef Bernadt CT, Collins BT (2017) Fine-needle aspiration biopsy of HPV-related squamous cell carcinoma of the head and neck: current ancillary testing methods for determining HPV status. Diagn Cytopathol 45:221–229CrossRef
5.
Zurück zum Zitat Knoepp SM, Roh MH (2013) Ancillary techniques on direct-smear aspirate slides a significant evolution for cytopathology techniques. Cancer Cytopathol 121:120–128CrossRef Knoepp SM, Roh MH (2013) Ancillary techniques on direct-smear aspirate slides a significant evolution for cytopathology techniques. Cancer Cytopathol 121:120–128CrossRef
6.
Zurück zum Zitat Faquin WC (2014) Human papillomavirus (HPV) assays for testing fine-needle aspiration specimens in patients with head and neck squamous cell carcinoma. Cancer Cytopathol 122:92–95CrossRef Faquin WC (2014) Human papillomavirus (HPV) assays for testing fine-needle aspiration specimens in patients with head and neck squamous cell carcinoma. Cancer Cytopathol 122:92–95CrossRef
7.
Zurück zum Zitat Sivars L, Tani E, Näsman A, Ramqvist T, Munck-Wikland E, Dalianis T (2016) Human papillomavirus as a diagnostic and prognostic tool in cancer of unknown primary in the head and neck region. Anticancer Res 36:487–493PubMed Sivars L, Tani E, Näsman A, Ramqvist T, Munck-Wikland E, Dalianis T (2016) Human papillomavirus as a diagnostic and prognostic tool in cancer of unknown primary in the head and neck region. Anticancer Res 36:487–493PubMed
8.
Zurück zum Zitat Rollo F, Dona’ MG, Pellini R, Pichi B, Marandino F, Covello R et al (2018) Cytology and direct human papillomavirus testing on fine needle aspirates from cervical lymph node metastases of patients with oropharyngeal squamous cell carcinoma or occult primary. Cytopathology 29:449–454CrossRef Rollo F, Dona’ MG, Pellini R, Pichi B, Marandino F, Covello R et al (2018) Cytology and direct human papillomavirus testing on fine needle aspirates from cervical lymph node metastases of patients with oropharyngeal squamous cell carcinoma or occult primary. Cytopathology 29:449–454CrossRef
9.
Zurück zum Zitat Channir HI, Grønhøj Larsen C, Ahlborn LB, van Overeem HT, Gerds TA, Charabi BW et al (2016) Validation study of HPV DNA detection from stained FNA smears by polymerase chain reaction: improving the diagnostic workup of patients with a tumor on the neck. Cancer Cytopathol 124:820–827CrossRef Channir HI, Grønhøj Larsen C, Ahlborn LB, van Overeem HT, Gerds TA, Charabi BW et al (2016) Validation study of HPV DNA detection from stained FNA smears by polymerase chain reaction: improving the diagnostic workup of patients with a tumor on the neck. Cancer Cytopathol 124:820–827CrossRef
10.
Zurück zum Zitat Lewis JS, Beadle B, Bishop JA, Chernock RD, Colasacco C, Lacchetti C et al (2018) Human papillomavirus testing in head and neck carcinomas: guideline from the college of American pathologists. Arch Pathol Lab Med 142:559–597CrossRef Lewis JS, Beadle B, Bishop JA, Chernock RD, Colasacco C, Lacchetti C et al (2018) Human papillomavirus testing in head and neck carcinomas: guideline from the college of American pathologists. Arch Pathol Lab Med 142:559–597CrossRef
11.
Zurück zum Zitat Holmes B, Westra WH (2014) The expanding role of cytopathology in the diagnosis of HPV-related squamous cell carcinoma of the head and neck. Diagn Cytopathol 42:85–93CrossRef Holmes B, Westra WH (2014) The expanding role of cytopathology in the diagnosis of HPV-related squamous cell carcinoma of the head and neck. Diagn Cytopathol 42:85–93CrossRef
12.
Zurück zum Zitat Roy-Chowdhuri S, Krishnamurthy S (2014) The role of cytology in the era of HPV-related head and neck carcinoma. Semin Diagn Pathol 32:250–257CrossRef Roy-Chowdhuri S, Krishnamurthy S (2014) The role of cytology in the era of HPV-related head and neck carcinoma. Semin Diagn Pathol 32:250–257CrossRef
13.
Zurück zum Zitat Westra WH (2014) Detection of human papillomavirus (HPV) in clinical samples: evolving methods and strategies for the accurate determination of HPV status of head and neck carcinomas. Oral Oncol 50:771–779CrossRef Westra WH (2014) Detection of human papillomavirus (HPV) in clinical samples: evolving methods and strategies for the accurate determination of HPV status of head and neck carcinomas. Oral Oncol 50:771–779CrossRef
14.
Zurück zum Zitat Pusztaszeri MP, Faquin WC (2015) Cytologic evaluation of cervical lymph node metastases from cancers of unknown primary origin. Semin Diagn Pathol 32:32–41CrossRef Pusztaszeri MP, Faquin WC (2015) Cytologic evaluation of cervical lymph node metastases from cancers of unknown primary origin. Semin Diagn Pathol 32:32–41CrossRef
16.
Zurück zum Zitat Kubik MW, Channir HI, Rubek N, Kim S, Ferris RL, von Buchwald C et al (2021) TORS base-of-tongue mucosectomy in human papilloma virus-negative carcinoma of unknown primary. Laryngoscope 131:78–81CrossRef Kubik MW, Channir HI, Rubek N, Kim S, Ferris RL, von Buchwald C et al (2021) TORS base-of-tongue mucosectomy in human papilloma virus-negative carcinoma of unknown primary. Laryngoscope 131:78–81CrossRef
17.
Zurück zum Zitat van Weert S, Rijken JA, Plantone F, Bloemena E, Vergeer MR, Lissenberg- Witte BI et al (2020) A systematic review on Transoral robotic surgery (TORS) for carcinoma of unknown primary origin: Has tongue base mucosectomy become indispensable? Clin Otolaryngol 45:732–738CrossRef van Weert S, Rijken JA, Plantone F, Bloemena E, Vergeer MR, Lissenberg- Witte BI et al (2020) A systematic review on Transoral robotic surgery (TORS) for carcinoma of unknown primary origin: Has tongue base mucosectomy become indispensable? Clin Otolaryngol 45:732–738CrossRef
18.
Zurück zum Zitat R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing 2015. R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing 2015.
19.
Zurück zum Zitat Sivars L, Landin D, Haeggblom L, Tertipis N, Grün N, Bersani C et al (2017) Human papillomavirus DNA detection in fine-needle aspirates as indicator of human papillomavirus-positive oropharyngeal squamous cell carcinoma: a prospective study. Head Neck 39:419–426CrossRef Sivars L, Landin D, Haeggblom L, Tertipis N, Grün N, Bersani C et al (2017) Human papillomavirus DNA detection in fine-needle aspirates as indicator of human papillomavirus-positive oropharyngeal squamous cell carcinoma: a prospective study. Head Neck 39:419–426CrossRef
20.
Zurück zum Zitat Lewis JS (2020) Human papillomavirus testing in head and neck squamous cell carcinoma in 2020: Where Are We Now and Where Are We Going? Head Neck Pathol 14:321–329CrossRef Lewis JS (2020) Human papillomavirus testing in head and neck squamous cell carcinoma in 2020: Where Are We Now and Where Are We Going? Head Neck Pathol 14:321–329CrossRef
21.
Zurück zum Zitat Wai KC, Strohl MP, van Zante A, Ha PK (2020) Molecular diagnostics in human papillomavirus-related head and neck squamous cell carcinoma. Cells 9:500CrossRef Wai KC, Strohl MP, van Zante A, Ha PK (2020) Molecular diagnostics in human papillomavirus-related head and neck squamous cell carcinoma. Cells 9:500CrossRef
22.
Zurück zum Zitat Jalaly JB, Hosseini SM, Shafique K, Baloch ZW (2020) Current status of p16 immunohistochemistry and HPV testing in fine needle aspiration specimens of the head and neck. Acta Cytol 64:30–39CrossRef Jalaly JB, Hosseini SM, Shafique K, Baloch ZW (2020) Current status of p16 immunohistochemistry and HPV testing in fine needle aspiration specimens of the head and neck. Acta Cytol 64:30–39CrossRef
23.
Zurück zum Zitat Qureishi A, Mawby T, Fraser L, Shah KA, Møller H, Winter S (2017) Current and future techniques for human papilloma virus (HPV) testing in oropharyngeal squamous cell carcinoma. Eur Arch Oto-Rhino-Laryngol 274:2675–2683CrossRef Qureishi A, Mawby T, Fraser L, Shah KA, Møller H, Winter S (2017) Current and future techniques for human papilloma virus (HPV) testing in oropharyngeal squamous cell carcinoma. Eur Arch Oto-Rhino-Laryngol 274:2675–2683CrossRef
24.
Zurück zum Zitat Wright MF, Weiss VL, Lewis JS, Schmitz JE, Ely KA (2020) Determination of high-risk HPV status of head and neck squamous cell carcinoma using the Roche cobas HPV test on cytologic specimens and acellular supernatant fluid. Cancer Cytopathol 128:482–490CrossRef Wright MF, Weiss VL, Lewis JS, Schmitz JE, Ely KA (2020) Determination of high-risk HPV status of head and neck squamous cell carcinoma using the Roche cobas HPV test on cytologic specimens and acellular supernatant fluid. Cancer Cytopathol 128:482–490CrossRef
25.
Zurück zum Zitat Stevens TM, Bishop JA (2017) HPV-related carcinomas of the head and neck: morphologic features, variants, and practical considerations for the surgical pathologist. Virchows Arch 471:295–307CrossRef Stevens TM, Bishop JA (2017) HPV-related carcinomas of the head and neck: morphologic features, variants, and practical considerations for the surgical pathologist. Virchows Arch 471:295–307CrossRef
26.
Zurück zum Zitat Mirghani H, Casiraghi O, Amen F, He M, Ma X-J, Saulnier P et al (2015) Diagnosis of HPV-driven head and neck cancer with a single test in routine clinical practice. Mod Pathol 28:1518–1527CrossRef Mirghani H, Casiraghi O, Amen F, He M, Ma X-J, Saulnier P et al (2015) Diagnosis of HPV-driven head and neck cancer with a single test in routine clinical practice. Mod Pathol 28:1518–1527CrossRef
27.
Zurück zum Zitat Jalaly JB, Lewis JS, Collins BT et al (2015) Correlation of p16 immunohistochemistry in FNA biopsies with corresponding tissue specimens in HPV-related squamous cell carcinomas of the oropharynx. Cancer Cytopathol 123:723–731CrossRef Jalaly JB, Lewis JS, Collins BT et al (2015) Correlation of p16 immunohistochemistry in FNA biopsies with corresponding tissue specimens in HPV-related squamous cell carcinomas of the oropharynx. Cancer Cytopathol 123:723–731CrossRef
28.
Zurück zum Zitat Channir HI, Kiss K, Rubek N, Andersen J, Georgsen JB, Rathje GS et al (2018) Comparison of clinical, radiological and morphological features including the distribution of HPV E6/E7 oncogenes in resection specimens of oropharyngeal squamous cell carcinoma. Oral Oncol 78:163–170CrossRef Channir HI, Kiss K, Rubek N, Andersen J, Georgsen JB, Rathje GS et al (2018) Comparison of clinical, radiological and morphological features including the distribution of HPV E6/E7 oncogenes in resection specimens of oropharyngeal squamous cell carcinoma. Oral Oncol 78:163–170CrossRef
Metadaten
Titel
Human papillomavirus testing in metastatic squamous cell carcinoma of the neck with unknown primary using PCR on fine-needle aspiration smears: a prospective clinical study
verfasst von
Hani Ibrahim Channir
Anne Fog Lomholt
Thomas Alexander Gerds
Birgitte Wittenborg Charabi
Katalin Kiss
Christian von Buchwald
Publikationsdatum
24.10.2021
Verlag
Springer Berlin Heidelberg
Erschienen in
European Archives of Oto-Rhino-Laryngology / Ausgabe 6/2022
Print ISSN: 0937-4477
Elektronische ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-021-07133-5

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