Expression and Diagnostic Implication of HPV and p16 in Squamous Cell Carcinoma in Multiple Organ Sites.
Oluyomi Asojo, Kathryn Wikenheiser-Brokamp, Gayle Hill, Fred Lucas, Chris Hackett, Qihui Jim Zhai. Univ. of Cincinnati, OH
Background: p16 is a cell cycle regulatory protein which maintains tumor supressor activity of pRb gene. Following integration of human papilloma (HPV) viral DNA into host genome, HPV E7 protein degrades pRb resulting in p16 upregulation. HPV has been implicated in squamous cell carcinoma (SCC) in anogenital and upper aerodigestive tracts. Its role in lung SCC is controversial. Studies imply usefulness of p16 in discriminating between cervical SCC with lung metastases and primary lung SCC. We study the presence of HPV16 and the expression p16 in SCC in multiple sites to determine its usefulness as a marker in these sites.
Design: 56 cases of primary SCC were retrieved from our pathology archives. H&E stained slides were reviewed by 2 independent pathologists. Sites were lung: 25 cases, anogenital area: 8 cases, esophagus: 5 cases, skin: 7 cases, head/neck: 11 cases. Cases varied from well to moderately differentiated SCC. Insitu hybiridization (ISH) for HPV16 and p16 immunohistochemical analysis were performed on paraffin sections using an automated system (Ventana 1:200). Scoring for p16 expression was based on proportion of positive cells as follows: negative 0:<10%, weak 1+:10-30%, moderate 2+:50-75%, strong 3+:75-100%. Nuclear or combined nuclear and cytoplasmic stains were considered specific for p16. HPV16 ISH was scored as positive or negative based on nuclear positivity.
Results: Of 25 cases of lung SCC, 40% were positive for p16. Proportion of positive cells was independent of degree of differentiation. All cases from the anogenital area, 40% of skin SCC, 27.3% of head/neck SCC were positive for p16. All cases of esophagus were negative for p16.
By ISH, HPV16 was detected in 4% of lung SCC, 37.5% of anogenital SCC and 27.3% of head/neck SCC. There was no detection of HPV16 in all cases of esophageal and skin SCC.
|P16 immunoreactivity score||HPV16 ISH|
|SCC site||Number of cases||0||1+||2+||3+||Positive||Negative|