Evidence of the causal role of human papillomavirus type 58 in an oropharyngeal carcinoma

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.

Figure 1

E6 and E7 antibodies status for HPV58 and other HPV types (16, 18, 31, 33, 45, 52, 6 and 11). MFI (Mean Fluorescence Intensity) values (y axis) are shown for the early proteins E6 and E7 of HPV58 and other HPV types (16, 18, 31, 33, 45, 6, 11) (x axis). Left: E6 and E7 MFI values for HPV58; Center and right: the MFI values for the other HPV types tested, grouped as E6 and E7, respectively.

Figure 2

Immunohistochemistry of cellular proteins p16^INK4a and pRb. A and C, p16^INK4a expression in normal tumor-adjacent mucosa (M) and in tumor (T) tissue, respectively. B and D, pRb expression in normal tumor-adjacent mucosa and in tumor tissue, respectively. S, stroma. Original magnification 10×. p16^INK4a low in the normal tumor-adjacent mucosa (blue-stained nuclei (A)), high in the tumor (brown stained nuclei (C)). pRb high in normal tumor-adjacent mucosa (brown-stained nuclei (B)), low in the tumor (blue-stained nuclei (D)).