Positive Linear Relationship between Nucleophosmin Protein Expression and the Viral Load in HPV-Associated Oropharyngeal Squamous Cell Carcinoma: A Possible Tool for Stratification of Patients

• Published in: International journal of molecular sciences 2023-02, Vol.24 (4), p.3482
• Main Authors: D'Agostino, Marco, Di Cecco, Marco, Marani, Carla, Vigili, Maurizio Giovanni, Sileno, Sara, Volpi, Chiara Costanza, Gloghini, Annunziata, Avitabile, Daniele, Magenta, Alessandra, Rahimi, Siavash
• Format: Article
• Language: English
• Subjects: Apoptosis; Biosynthesis; Carcinoma, Squamous Cell - pathology; Cell cycle; Cervical cancer; Chemoradiotherapy; Communication; Cyclin-Dependent Kinase Inhibitor p16; Development and progression; DNA biosynthesis; DNA damage; DNA repair; DNA, Viral - genetics; Gene expression; Genomes; Head and Neck Neoplasms; HPV; Human papillomavirus; Human Papillomavirus Viruses; Humans; Hybridization; Hypotheses; Infections; Inflammation; Kinases; Medical research; Medicine, Experimental; Nucleoli; Nucleophosmin; Oncogene Proteins, Viral - genetics; Oropharyngeal Neoplasms - pathology; oropharyngeal squamous cell carcinoma; Oropharyngolaryngeal carcinoma; Pap smear; Papillomaviridae - genetics; Papillomavirus Infections; Proteins; Retrospective Studies; Risk factors; RNA polymerase; Smoking; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Throat cancer; Viral Load; Viruses
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24043482

Most oropharyngeal squamous cell carcinomas (OPSCCs) are human papillomavirus (HPV)-associated, high-risk (HR) cancers that show a better response to chemoradiotherapy and are associated with improved survival. Nucleophosmin (NPM, also called NPM1/B23) is a nucleolar phosphoprotein that plays different roles within the cell, such as ribosomal synthesis, cell cycle regulation, DNA damage repair and centrosome duplication. NPM is also known as an activator of inflammatory pathways. An increase in NPM expression has been observed in vitro in E6/E7 overexpressing cells and is involved in HPV assembly. In this retrospective study, we investigated the relationship between the immunohistochemical (IHC) expression of NPM and HR-HPV viral load, assayed by RNAScope in situ hybridization (ISH), in ten patients with histologically confirmed p16-positive OPSCC. Our findings show that there is a positive correlation between NPM expression and HR-HPV mRNA (Rs = 0.70, = 0.03), and a linear regression (r = 0.55; = 0.01). These data support the hypothesis that NPM IHC, together with HPV RNAScope, could be used as a predictor of transcriptionally active HPV presence and tumor progression, which is useful for therapy decisions. This study includes a small cohort of patients and, cannot report conclusive findings. Further studies with large series of patients are needed to support our hypothesis.