HPV Infection in Squamous Cell Carcinoma of the Hypopharynx, Larynx, and Oropharynx With Multisite Involvement.
Humans
Papillomavirus Infections
/ complications
Hypopharynx
/ pathology
Retrospective Studies
Carcinoma, Squamous Cell
/ pathology
Squamous Cell Carcinoma of Head and Neck
Prognosis
Head and Neck Neoplasms
Oropharynx
/ pathology
Larynx
/ pathology
Oropharyngeal Neoplasms
Cyclin-Dependent Kinase Inhibitor p16
/ genetics
Papillomaviridae
/ genetics
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
01 09 2023
01 09 2023
Historique:
medline:
17
8
2023
pubmed:
26
6
2023
entrez:
26
6
2023
Statut:
ppublish
Résumé
The prevalence and prognostic significance of high-risk human papillomavirus (HR-HPV) have been well-established in oropharyngeal squamous cell carcinoma (OPSCC), but not in hypopharyngeal squamous cell carcinoma (HPSCC) or laryngeal squamous cell carcinoma (LSCC). Moreover, HR-HPV infection in squamous cell carcinoma with multisite involvement has not been examined. To clarify these issues, we retrospectively collected 480 invasive tumors from 467 patients with HPSCC, LSCC, or OPSCC, and comprehensively analyzed the detailed tumor localization, transcriptionally active HR-HPV infection by messenger RNA in situ hybridization, and immunohistochemical staining for p16 and Rb. HR-HPV infection was observed in 115/480 tumors (24%). Human papillomavirus (HPV)-positive cases were closely related with p16 positivity and the partial loss pattern of Rb. HR-HPV was detected in 104 of 161 tumors (64.6%) in the pure OPSCC group and only 1 of 253 tumors (0.4%) in the pure HP/LSCC group; the positive case occurred in the vocal cords. In the multisite-involving combined-type squamous cell carcinoma group, HPV infection was observed in 10/40 (25%) cases, and the 10 HPV-positive cases had OPSCC extending to the larynx or hypopharynx. Among high T-stage (T3/T4) cases of pure OPSCC, HPV-positive cases showed a better prognosis ( P =0.0144), whereas the HPV-positive combined OPSCC group did not show a better prognosis ( P =0.9428), as compared with HPV-negative counterpart. The results suggest that HR-HPV infection in pure HPSCC and LSCC may be extremely rare. HR-HPV infection seems to be present in a substantial proportion of patients with combined OPSCC and HPSCC/LSCC, but it may not improve prognosis at such advanced disease stages. Confirmation of these points awaits future studies with larger cohorts.
Identifiants
pubmed: 37357948
doi: 10.1097/PAS.0000000000002086
pii: 00000478-202309000-00001
doi:
Substances chimiques
Cyclin-Dependent Kinase Inhibitor p16
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
955-966Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
Références
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–249.
Hashibe M, Brennan P, Benhamou S, et al. Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. J Natl Cancer Inst. 2007;99:777–789.
Nakajima A, Nishiyama K, Morimoto M, et al. A single-institution experience. Int J Radiat Oncol Biol Phys. 2012;82:e129–e135.
Shiotani A, Tomifuji M, Araki K, et al. Videolaryngoscopic transoral en bloc resection of supraglottic and hypopharyngeal cancers using laparoscopic surgical instruments. Ann Otol Rhinol Laryngol. 2010;119:225–232.
Wolf GT, Fisher SG, Hong WK, et al. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med. 1991;324:1685–1690.
Eckel HE, Bradley PJ. Treatment options for hypopharyngeal cancer. Adv Otorhinolaryngol. 2019;83:47–53.
Bishop JA, Ma XJ, Wang H, et al. Detection of transcriptionally active high-risk HPV in patients with head and neck squamous cell carcinoma as visualized by a novel E6/E7 mRNA in situ hybridization method. Am J Surg Pathol. 2012;36:1874–1882.
Allen CT, Lewis JS Jr, El-Mofty SK, et al. Human papillomavirus and oropharynx cancer: biology, detection and clinical implications. Laryngoscope. 2010;120:1756–1772.
Nakano T, Yamamoto H, Nakashima T, et al. Molecular subclassification determined by human papillomavirus and epidermal growth factor receptor status is associated with the prognosis of oropharyngeal squamous cell carcinoma. Hum Pathol. 2016;50:51–61.
Jiromaru R, Yamamoto H, Yasumatsu R, et al. p16 overexpression and Rb loss correlate with high-risk HPV infection in oropharyngeal squamous cell carcinoma. Histopathology. 2021;79:358–369.
Gelwan E, Malm IJ, Khararjian A, et al. Nonuniform distribution of high-risk human papillomavirus in squamous cell carcinomas of the oropharynx: rethinking the anatomic boundaries of oral and oropharyngeal carcinoma from an oncologic HPV perspective. Am J Surg Pathol. 2017;41:1722–1728.
Jiromaru R, Yamamoto H, Yasumatsu R, et al. HPV-related sinonasal carcinoma: clinicopathologic features, diagnostic utility of p16 and Rb immunohistochemistry, and EGFR copy number alteration. Am J Surg Pathol. 2020;44:305–315.
Bishop JA, Guo TW, Smith DF, et al. Human papillomavirus-related carcinomas of the sinonasal tract. Am J Surg Pathol. 2013;37:185–192.
Larque AB, Hakim S, Ordi J, et al. High-risk human papillomavirus is transcriptionally active in a subset of sinonasal squamous cell carcinomas. Mod Pathol. 2014;27:343–351.
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.
Hongo T, Yamamoto H, Jiromaru R, et al. Clinicopathologic significance of EGFR mutation and HPV infection in sinonasal squamous cell carcinoma. Am J Surg Pathol. 2021;45:108–118.
Boyer SN, Wazer DE, Band V. E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway. Cancer Res. 1996;56:4620–4624.
Hughes RT, Beuerlein WJ, O’Neill SS, et al. Human papillomavirus-associated squamous cell carcinoma of the larynx or hypopharynx: clinical outcomes and implications for laryngeal preservation. Oral Oncol. 2019;98:20–27.
Castellsagué X, Alemany L, Quer M, et al. HPV involvement in head and neck cancers: comprehensive assessment of biomarkers in 3680 patients. J Natl Cancer Inst. 2016;108:djv403.
Hernandez BY, Goodman MT, Lynch CF, et al. Human papillomavirus prevalence in invasive laryngeal cancer in the United States. PLoS One. 2014;9:e115931.
Kiyuna A, Ikegami T, Uehara T, et al. High-risk type human papillomavirus infection and p16 expression in laryngeal cancer. Infect Agent Cancer. 2019;14:8.
Lewis JS Jr, Ukpo OC, Ma XJ, et al. Transcriptionally-active high-risk human papillomavirus is rare in oral cavity and laryngeal/hypopharyngeal squamous cell carcinomas—a tissue microarray study utilizing E6/E7 mRNA in situ hybridization. Histopathology. 2012;60:982–991.
Lewis JS Jr, Beadle B, Bishop JA, et al. Human papillomavirus testing in head and neck carcinomas: guideline from the College of American Pathologists. Arch Pathol Lab Med. 2018;142:559–597.
Fakhry C, Lacchetti C, Rooper LM, et al. Human papillomavirus testing in head and neck carcinomas: ASCO Clinical Practice Guideline Endorsement of the College of American Pathologists Guideline. J Clin Oncol. 2018;36:3152–3161.
El-Naggar AK, Chan JKC, Rubin Grandis J, et al. WHO Classification of Head and Neck Tumours, 4th ed. International Agency for Research on Cancer; 2017.
Brierley J, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Tumours, 8th ed. John Wiley & Sons Inc.; 2017.
Vermorken JB, Psyrri A, Mesía R, et al. Impact of tumor HPV status on outcome in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck receiving chemotherapy with or without cetuximab: retrospective analysis of the phase III EXTREME trial. Ann Oncol. 2014;25:801–807.
Westra WH. The morphologic profile of HPV-related head and neck squamous carcinoma: implications for diagnosis, prognosis, and clinical management. Head Neck Pathol. 2012;6:48–54.
Zito Marino F, Ronchi A, Stilo M, et al. Multiplex HPV RNA in situ hybridization/p16 immunohistochemistry: a novel approach to detect papillomavirus in HPV-related cancers. A novel multiplex ISH/IHC assay to detect HPV. Infect Agent Cancer. 2020;15:46.
Keung ES, Souers RJ, Bridge JA, et al. Comparative performance of high-risk human papillomavirus RNA and DNa in situ hybridization on College of American Pathologists Proficiency Tests. Arch Pathol Lab Med. 2020;144:344–349.
Hongo T, Yamamoto H, Tanabe M, et al. High-risk HPV-related squamous cell carcinoma in the conjunctiva and lacrimal sac: clinicopathologic characteristics and diagnostic utility of p16 and Rb immunohistochemistry. Am J Surg Pathol. 2022;46:977–987.
Mirkovic J, Howitt BE, Roncarati P, et al. Carcinogenic HPV infection in the cervical squamo-columnar junction. J Pathol. 2015;236:265–271.
El-Naggar AK, Westra WH. p16 expression as a surrogate marker for HPV-related oropharyngeal carcinoma: a guide for interpretative relevance and consistency. Head Neck. 2012;34:459–461.
Schlecht NF, Brandwein-Gensler M, Nuovo GJ, et al. A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer. Mod Pathol. 2011;24:1295–1305.
Economopoulou P, Kotsantis I, Psyrri A. De-escalating strategies in HPV-associated head and neck squamous cell carcinoma. Viruses. 2021;13:1787.
Nagarsheth NB, Norberg SM, Sinkoe AL, et al. TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers. Nat Med. 2021;27:419–425.
Quayle SN, Girgis N, Thapa DR, et al. CUE-101, a novel E7-pHLA-IL2-Fc fusion protein, enhances tumor antigen-specific T-cell activation for the treatment of HPV16-driven malignancies. Clin Cancer Res. 2020;26:1953–1964.
Doran SL, Stevanović S, Adhikary S, et al. T-cell receptor gene therapy for human papillomavirus–associated epithelial cancers: a first-in-human, phase I/II study. J Clin Oncol. 2019;37:2759–2768.
Massarelli E, William W, Johnson F, et al. Combining immune checkpoint blockade and tumor-specific vaccine for patients with incurable human papillomavirus 16–related cancer. JAMA Oncol. 2019;5:67.