Abstract
Persistent human papillomavirus infection (HPV) is recognized as an important etiologic factor for a subset of head and neck squamous cell carcinomas (SCC), especially those arising from the oropharynx. Whereas HPV16 accounts for the majority of HPV DNA-positive oropharyngeal SCC, infections with other mucosal high-risk HPV types are quite rare and biological data demonstrating their causal involvement are insufficient. Here we present the first case of an oropharyngeal SCC driven by HPV type 58. A 69-year-old Caucasian woman presented with an enlarged and firm left tonsil. A computed tomography scan showed a left tonsillar mass, extending to the soft palate and the glossotonsillar sulcus. The patient underwent extended radical tonsillectomy and ipsilateral selective neck dissection. Pathology confirmed an infiltrating, poorly differentiated SCC of the left tonsil with node metastasis (pT2N1). Adjuvant external beam radiation therapy (60 Grays (Gy)) was administered. After 1 year of follow-up, the patient is well with no evidence of cancer recurrence. HPV analyses of the tumor tissue by BSGP5+/6+ −PCR/MPG, targeting 51 mucosal HPV types, showed single positivity for HPV type 58. Presence of HPV58 E6*I RNA demonstrated biological activity of the virus in the tumor tissue, and presence of serum antibodies to HPV58 oncoproteins E6 and E7 indicated presence of an HPV58-driven cancer. Overexpression of cellular protein p16INK4a and reduced expression of pRb, two cellular markers for HPV-induced cell transformation, were observed. Exons 4–10 of TP53 showed no mutations or polymorphisms. The presence of HPV58 as single HPV infection in combination with a broad variety of direct and indirect markers of HPV transformation provides comprehensive evidence that this oropharyngeal SCC was driven by HPV58.
Highlights
Oropharyngeal squamous cell carcinomas (OPSCC) are categorized as head and neck squamous cell carcinoma (HNSCC) together with squamous cell carcinoma of the oral cavity, larynx and hypopharynx
OPSCC account for approximately 50,000 incident cases [1,2], and together with hypopharyngeal squamous cell carcinomas they account for about 1.1% of all malignancies worldwide [3]
While human papillomavirus infection (HPV) type 16 is the most prevalent type in Cervical carcinoma (CxCa) worldwide (61%), the other carcinogenic types, i.e. HPV18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 are responsible for approximately another 33% of CxCa, with HPV58 accounting for 2% of CxCa
Summary
Oropharyngeal squamous cell carcinomas (OPSCC) are categorized as head and neck squamous cell carcinoma (HNSCC) together with squamous cell carcinoma of the oral cavity, larynx and hypopharynx. In patients with invasive HPV-driven cervical, penile and oropharyngeal SCC overexpression of E6 and E7 oncoproteins frequently leads to strong antibody responses against these viral proteins [4,16,17,18,19,20,21,22,23,24] This model has been extensively verified in cervical carcinoma for all HPV types classified by IARC/WHO as carcinogenic, probably and possibly carcinogenic [25]. HPV genotyping was performed by BSGP5+/6+ −PCR/ MPG [31,32,33], an assay capable of amplifying about 150 base pairs (bp) of the L1 gene of 51 HPV mucosal types, followed by hybridization to type-specific probes on fluorescent suspension array beads It includes detection of the human β-globin gene as DNA quality control as well as internal PCR and hybridization controls.
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