Human Papillomavirus Is Rare and Does Not Correlate with p16(INK4A) Expression in Non-Small-Cell Lung Cancer in a Jordanian Subpopulation

在约旦亚人群中,人乳头瘤病毒感染罕见,且与非小细胞肺癌中的p16(INK4A)表达无关。

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Abstract

Background and Objectives: Human papillomavirus (HPV) was previously investigated in lung cancer with wide inter-geographic discrepancies. p16(INK4a) has been used as a surrogate for detecting high-risk HPV (HR-HPV) in some cancer types. This study assessed the evidence of HPV in non-small-cell lung cancer (NSCLC) among Jordanian patients, investigated the expression of p16(INK4a), and evaluated its prognostic value and association with HPV status. Materials and Methods: The archived samples of 100 patients were used. HPV DNA detection was performed by real-time polymerase chain reaction (RT-PCR). p16(INK4a) expression was assessed by immunohistochemistry (IHC). The Eighth American Joint Committee on Cancer protocol (AJCC) of head and neck cancer criteria were applied to evaluate p16(INK4a) positivity considering a moderate/strong nuclear/cytoplasmic expression intensity with a distribution in ≥75% of cells as positive. Results: HPV DNA was detected in 5% of NSCLC cases. Three positive cases showed HR-HPV subtypes (16, 18, 52), and two cases showed the probable HR-HPV 26 subtype. p16(INK4a) expression was positive in 20 (20%) NSCLC cases. None of the HPV-positive tumors were positive for p16(INK4a) expression. A statistically significant association was identified between p16(INK4a) expression and the pathological stage (p = 0.029) but not with other variables. No survival impact of p16(INK4a) expression was detected in NSCLC cases as a group; however, it showed a statistically significant association with overall survival (OS) in squamous cell carcinoma (SqCC) cases (p = 0.033). Conclusions: This is the first study to assess HPV and p16(INK4a) expression in a Jordanian population. HPV positivity is rare in NSCLC among a Jordanian subpopulation. P16 (INK4a) reliability as a surrogate marker for HPV infection in lung cancer must be revisited.

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