Spindle Cell Carcinomas of the Head and Neck Rarely Harbor Transcriptionally-Active Human Papillomavirus

Abstract

Spindle cell carcinoma is an uncommon variant of squamous cell carcinoma characterized by spindled or pleomorphic cells which appear to be a true sarcoma but are actually epithelial. Some head and neck squamous cell carcinoma variants can be human papillomavirus (HPV)-related and have improved outcomes. We sought to determine if spindle cell carcinomas are associated with transcriptionally-active HPV. Cases of spindle cell carcinoma were retrieved from department files. Transcriptionally-active HPV was determined by mRNA in situ hybridization for high risk HPV E6 and E7 transcripts and by a surrogate marker, p16 immunohistochemistry, with a 50% staining cutoff. RT-PCR for high risk HPV mRNA was performed on the cases that were technical failures by in situ hybridization. Medical records and follow up information were retrieved for all patients. Of 31 cases, 5 were from the oropharynx, 12 from the oral cavity, and 14 from the larynx or hypopharynx. One purely spindled oral cavity spindle cell carcinoma was HPV positive. It was also diffusely positive for p16. Another laryngeal spindle cell carcinoma was HPV positive in both the squamous and spindle cell components, but was negative for p16. None of the five oropharyngeal spindle cell carcinomas were positive for p16 or HPV RNA. The HPV positive patients both presented at high stage (IV) and died with disease within 2 years of diagnosis. The majority of spindle cell carcinomas of the head and neck, including those arising in the oropharynx, are not related to transcriptionally active HPV. Although the number of cases is too small for any definitive conclusions, for the rare HPV positive spindle cell carcinoma cases, positive viral status does not appear to confer any prognostic benefit.

Use of p40 and p63 Immunohistochemistry and Human Papillomavirus Testing as Ancillary Tools for the Recognition of Head and Neck Sarcomatoid Carcinoma and Its Distinction From Benign and Malignant Mesenchymal Processes

“…44 Using an HPV detection approach that incorporates p16 immunohistochemical staining together with HPV16 DNA in situ hybridization, HPV was identified in both the conventional and spindle cell components of 3 (10%) SCs. This approach was particularly useful in the oropharynx—the site most commonly targeted by high-risk HPV—where HPV was detected in 30% of the SCs.…”

“…For example, HPV is consistently detected in HPV-related cancers that recur, sometimes long after treatment of the primary tumor, 40,41 and it is detected in HPV-related carcinomas that have undergone transformation to small cell carcinoma. 42,43 Recently, Watson et al 44 detected HPV in 2 SCs of the head and neck, suggesting that HPV testing could also be used as an ancillary diagnostic tool in the evaluation of spindle cell lesions of the head and neck.…”

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What is New in the 2017 WHO Blue Book for Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space

“…In addition, most spindle cell carcinoma (SpCC), an uncommon variant of CSCC, including those arising in the oropharynx, is not related to transcriptionally active HPV [37]. However, in relation to SpCC histogenesis, which is only briefly mentioned in WHO 2017, it is important to highlight that SpCC is a monoclonal neoplasm originating from a non-committed stem cell, giving rise to both epithelial and mesenchymal components [38,39].…”

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Oropharynx

“…It also includes, as recently described in small patient series, the presence of ciliated tumor cells "ciliated adenosquamous carcinoma". Although the number of reported cases of these variant forms is limited, the best available data suggests that patients with transcriptionally-active HPV have clinical outcomes that are similar to HPV-positive OPSCC with typical morphology [11][12][13][14][15][16][17][18][19][20][21].…”