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p16+ pulmonary squamous cell carcinoma

Friday 8 April 2016

p16+ pulmonary SCC

High-risk human papillomavirus (hrHPV) is an etiologic agent in squamous cell carcinoma (SqCC) arising in the oropharynx and cervix, and a proven prognostic factor in oropharyngeal SqCC. Many studies have found HPV in non-small cell lung carcinoma (NSCLC).

Recent studies advocate the detection of messenger RNA transcripts of E6/E7 as more reliable evidence of transcriptively active HPV in tumor cells. The clinical significance of finding HPV remains unclear in NSCLC. Punctate nuclear hybridization signals by DNA-ISH in the malignant cells defined an HPV-positive carcinoma.

In a study, expression of p16 was scored as positive if at least 70% of tumor cells of PSCC showed diffuse and strong nuclear and cytoplasmic staining. In thi study, of the 196 patients (range, 33-87 years; 108 men), p16 was positive in 19 ADCs and 9 SqCCs, but HPV DNA-ISH and RNA-ISH were negative in all cases. (26342243)

This study did not detect HPV infection by DNA-ISH or RNA-ISH in any cases of primary NSCLC despite positive p16 expression in a portion of ADC and SqCC.

p16 should therefore not be used as a surrogate marker for HPV infection in NSCLC. (26342243, 25544708)

In pulmonary SCC, there is no association between the presence of HPV DNA and the expression of p16 protein. (22843877)

Furthermore, the loss of the p16 gene and the instability of chromosome 9 were frequently found in HPV DNA-negative cases. (22843877)

References

- Detection of human papillomavirus in non-small cell carcinoma of the lung. Chang SY, Keeney M, Law M, Donovan J, Aubry MC, Garcia J. Hum Pathol. 2015 Nov;46(11):1592-7. doi : 10.1016/j.humpath.2015.07.01 PMID: 26342243

- Correlation between squamous cell carcinoma of the lung and human papillomavirus infection and the relationship to expression of p53 and p16. Fan X, Yu K, Wu J, Shao J, Zhu L, Zhang J. Tumour Biol. 2015 Apr;36(4):3043-9. doi : 10.1007/s13277-014-2940-7 PMID: 25544708

- Human papilloma virus genome is rare in North American non-small cell lung carcinoma patients. Yanagawa N, Wang A, Kohler D, Santos Gda C, Sykes J, Xu J, Pintilie M, Tsao MS. Lung Cancer. 2013 Mar;79(3):215-20. doi : 10.1016/j.lungcan.2012.11.018 PMID: 23254264

- Human papillomavirus DNA and p16 gene in squamous cell lung carcinoma. Gatta LB, Balzarini P, Tironi A, Berenzi A, Benetti A, Angiero F, Grigolato P, Dessy E. Anticancer Res. 2012 Aug;32(8):3085-9. PMID: 22843877