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

Baboci L, Boscolo-Rizzo P, Holzinger D, Bertorelle R, Biasini L, Michel A, Schmitt M, Spinato G, Bussani R, Alemany L, Tirelli G, Da Mosto MC, Del Mistro A, Pawlita M - Virol. J. (2013)

Bottom Line: Pathology confirmed an infiltrating, poorly differentiated SCC of the left tonsil with node metastasis (pT2N1).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Veneto Institute of Oncology IOV - IRCCS, Immunology and Molecular Oncology Unit, Via Gattamelata, 64, Padua 35128-I, Italy. annarosa.delmistro@ioveneto.it.

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.

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Immunohistochemistry of cellular proteins p16INK4a and pRb. A and C, p16INK4a 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×. p16INK4a 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)).
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Figure 2: Immunohistochemistry of cellular proteins p16INK4a and pRb. A and C, p16INK4a 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×. p16INK4a 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)).

Mentions: The expression level of the cellular proteins p16INK4a and pRb, markers for HPV transformation, were evaluated by immunohistochemistry (IHC). The monoclonal antibodies CINtec (V-kit, MTM laboratories, Heidelberg, Germany) and NCL-RB (Novocastra, Newcastle, UK), were used for p16INK4a and pRb, respectively. Well characterized sections from CxCa and a healthy mucosa were used in each staining batch as reference for scoring of the protein expression levels for both markers. IHC was evaluated independently by two investigators. The tumor cells of the sections showed strong nuclear and diffuse cytoplasmic staining of p16INK4a (>95%) and low staining of pRb (<25%), while proliferating basal and parabasal cells of the tumor-adjacent mucosa showed low p16INK4a (<5%) and high pRb (>25%) expression (Figure 2).


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

Baboci L, Boscolo-Rizzo P, Holzinger D, Bertorelle R, Biasini L, Michel A, Schmitt M, Spinato G, Bussani R, Alemany L, Tirelli G, Da Mosto MC, Del Mistro A, Pawlita M - Virol. J. (2013)

Immunohistochemistry of cellular proteins p16INK4a and pRb. A and C, p16INK4a 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×. p16INK4a 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)).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842782&req=5

Figure 2: Immunohistochemistry of cellular proteins p16INK4a and pRb. A and C, p16INK4a 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×. p16INK4a 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)).
Mentions: The expression level of the cellular proteins p16INK4a and pRb, markers for HPV transformation, were evaluated by immunohistochemistry (IHC). The monoclonal antibodies CINtec (V-kit, MTM laboratories, Heidelberg, Germany) and NCL-RB (Novocastra, Newcastle, UK), were used for p16INK4a and pRb, respectively. Well characterized sections from CxCa and a healthy mucosa were used in each staining batch as reference for scoring of the protein expression levels for both markers. IHC was evaluated independently by two investigators. The tumor cells of the sections showed strong nuclear and diffuse cytoplasmic staining of p16INK4a (>95%) and low staining of pRb (<25%), while proliferating basal and parabasal cells of the tumor-adjacent mucosa showed low p16INK4a (<5%) and high pRb (>25%) expression (Figure 2).

Bottom Line: Pathology confirmed an infiltrating, poorly differentiated SCC of the left tonsil with node metastasis (pT2N1).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Veneto Institute of Oncology IOV - IRCCS, Immunology and Molecular Oncology Unit, Via Gattamelata, 64, Padua 35128-I, Italy. annarosa.delmistro@ioveneto.it.

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.

Show MeSH
Related in: MedlinePlus