Retrospectively, we correlated SLPI- and Annexin A2-expression with the HPV-status in chronic tonsilitis (CT; n=118) or tonsillar hyperplasia (H; n=96) tissue specimens, respectively, to analyse in non-neoplastic tonsillar tissue the inverse correlation between SLPI-expression and HPV-infection that was previously shown in HNSCC. We hypothesise that smoking induced up-regulation of SLPI results in a reduced binding of HPV to Annexin A2, a known modulator of HPV-entry in to the cell.
SLPI and p16INK4A-protein expression was measured by immunohistochemistry (IHC) in all 214 specimens; SLPI and Annexin A2 (AnxA2) gene expression was measured by RT-qPCR in 138 cases; DNA was isolated from all specimens to determine HPV-status. Results were correlated with patients' smoking habit.
In total 118 (55.1%) patients had CT (71 non-smokers; 47 smokers) and 94 (44.9%) had H (95 non-smokers; 1 smoker; 1 unknown). All samples were HPV-negative. p16INK4A-expression showed negative, weak, and moderate signals in 20 (9.3%),156 (72.9%), and 38 (17.8%) cases, respectively. SLPI protein-expression showed negative, weak, and moderate signals in 163 (76.2%), 45 (21.0%), and 6 (2.8%) cases, respectively. The correlation between smoking and SLPI was overall p=0.0001. Gene-expression analysis (n=138) showed that smoking (n=48) resulted in 5.39-fold increased SLPI-expression together with a 4.49-fold increase in AnxA2. A significant positive correlation between AnxA2 and SLPI indicating a surplus of AnxA2 in relation to SLPI was only found in the tonsillar tissue of non-smokers.
The data demonstrate that smoking not only, as previously shown results in HNSCC in increased SLPI- and AnxA2-expression, but show that this is also the case in non-neoplastic tonsillar tissue. The observed surplus of AnxA2 in relation to SLPI only found in the tonsillar tissue of non-smokers indicates a higher probability of a successful HPV-infection of the tonsillar tissue of non-smokers, given the properties of AnxA2 to function as an infection-modulator.The data demonstrate that smoking not only, as previously shown results in HNSCC in increased SLPI- and AnxA2-expression, but show that this is also the case in non-neoplastic tonsillar tissue. The observed surplus of AnxA2 in relation to SLPI only found in the tonsillar tissue of non-smokers indicates a higher probability of a successful HPV-infection of the tonsillar tissue of non-smokers, given the properties of AnxA2 to function as an infection-modulator.
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