Prognostic potential of Akt, pAkt(Ser473) and pAkt(Thr308) immunoreactivity in relation to HPV prevalence in head and neck squamous cell carcinoma patients

• Published in: Pathology, research and practice research and practice, 2022-01, Vol.229, p.153684-153684, Article 153684
• Main Authors: Janecka-Widła, Anna, Majchrzyk, Kaja, Mucha-Małecka, Anna, Słonina, Dorota, Biesaga, Beata
• Format: Article
• Language: English
• Subjects: Active HPV infection; Female; HNSCC; Humans; Independent prognostic factor; Male; Middle Aged; PAkt(Ser473); PAkt(Thr308); Papillomaviridae - isolation & purification; Phosphorylation; Prognosis; Proto-Oncogene Proteins c-akt - immunology; Proto-Oncogene Proteins c-akt - metabolism; Squamous Cell Carcinoma of Head and Neck - immunology; Squamous Cell Carcinoma of Head and Neck - virology; Survival
• ISSN: 0344-0338; 1618-0631
• DOI: 10.1016/j.prp.2021.153684

The prognosis of squamous cell carcinoma of head and neck (HNSCC) patients remains relatively poor over the last years. Tobacco, alcohol and active human papillomavirus (HPV) infection are involved in HNSCC development. Akt is a serine-threonine protein kinase with main phosphorylation sites at Thr308 and Ser473, which are critical to generate a high level of Akt activity. The aim of the study was to compare the expression and prognostic potential of total Akt and its 2 phosphorylated forms – pAkt(Ser473) and pAkt(Thr308) in relation to HPV status in HNSCC patients. The expression levels of proteins were assessed immunohistochemically. To select independent prognostic factors univariate and multivariate analyses with Cox proportional regression model were performed. Among HNSCC with active HPV16 infection significantly more tumors with high Akt (67.86%, p = 0.026) and low pAkt(Ser473) (64.29%, p = 0.000) expressions were found as compared to those with HPV negativity, while there was no significant difference in the pAkt(Thr308) expression level between HPV positive and negative tumors (p = 0.359). In the whole group of HNSCC patients independent favorable prognostic factors were low T stage, low pAkt(Thr308) expression, HPV16 active infection presence (for OS and DFS) and female gender (for OS only). Our results indicate an important role of pAkt(Thr308) as prognostic biomarker for HNSCC patients. There is a high probability that using Akt inhibitors would improve therapeutical benefits and treatment effectiveness, especially in HNSCC patients with high expression of pAkt. •Presence of active HPV16 was associated with high Akt and low pAkt(Ser473) levels.•Lack of difference in pAkt(Thr308) level between HPV positive and negative tumors.•Gender, T stage, pAkt(Thr308) & active HPV16 were independent prognostic factors.•Using Akt inhibitors could improve therapeutical benefits of HNSCC patients.