HPV infection is a strong prognostic marker in oropharyngeal squamous cell carcinomas (OSCCs). HPV-positive pts are associated with better survival than HPV-negative ones. Currently, the expression of p16 is the standard test to identify HPV positive OSCCs in clinical practice. The combined use of p16 and HPV DNA detection is the recommended standard for clinical research, at least in USA. In the present study we compare the prognostic value of a genomic viral fragment, E1, with p16 expression in a series of OSCC pts in terms of overall survival (OS) and progression free survival (PFS).
HPV was searched in 78 OSCC pts (63M/15F; median age 61; range 35-77) treated with chemoradiotherapy between 1997 and 2014. We used a specific E1 primer pair for HPV type 16 in a DNA-PCR assay on formalin-fixed paraffin-embedded (FFPE) tissues collected at diagnosis. Those primers were designed inside the coding region most frequently disrupted during viral integration in host chromosome, in order to get a fragment of 168 bp. Positivity for p16 was defined as ≥ 70% positive cells by IHC.
Twenty-six pts (33.4%) were HPV positive for E1 fragment, while 27 (34.6%) showed a pos ≥70% for p16. In terms of prognostic value, positive OSCC pts showed improved OS (p = 0.01 for E1 and p = 0.04 for p16) and PFS (p = 0.03 for E1 and p = 0.02 for p16), compared to negative ones. The concordance between p16 and E1 positivity was high (k = 0.74) and HPV power detection was similar to p16. Moreover, among positive p16 pts (n = 27), the E1 positive ones (n = 22) resulted to have a significant more favourable OS than the negative (n = 5) (p = 0.03). On the contrary, among positive E1 pts (n = 26), the p16 positive ones (n = 22) did not shown any difference in OS from the p16 negative ones (n = 4) (p = 0.25).
We observed a good concordance between p16 by IHC and E1 by DNA-PCR for HPV detection on FFPE tissues, in the present series of OSCCs. E1 might become a strong prognostic marker for OS and PFS in OSCCs and clinically as relevant as IHC for p16. Moreover the concurrent positivity for both markers (E1 + p16+) allowed the selection of pts with the best OS. When E1 and p16 resulted discordant, our data support the more accurate value of E1 in predicting OS.
Clinical trial identification
Legal entity responsible for the study
M.C. Merlano: Consultant for Merck Serono. All other authors have declared no conflicts of interest.