P27-11The prognostic utility of HPV specific testing in addition to p16 immunohistochemistry in oropharyngeal carcinoma.

27. HPV and oropharynx / Head and neck cancer
A. Santambrogio 1, H. Sathasivam 2, C. Andoniadou 1, M. Robinson 2, S. Thavaraj 1.
1King's College London (United Kingdom), 2Newcastle University (United Kingdom)

Background / Objectives

Patients with oropharyngeal squamous cell carcinoma (OpSCC) have significantly improved overall survival (OS) compared to matched HPV negative control groups. This observation has led to several ongoing clinical trials evaluating deintensification treatment strategies in HPV positive disease. Current guidance from UK national and professional organisations recommend p16 immunohistochemistry (IHC) as a minimum test which should ideally be followed by HPV-specific testing with DNA in situ hybridisation (ISH) in p16 positive cases.1,2 However, most UK diagnostic and treatment centres limit HPV testing to p16 IHC alone. Furthermore, several clinical trial protocols randomise patients according to p16 status alone without necessitating HPV specific testing. The objectives of this study were to:

1.     Determine the prevalence of p16 positive tumours lacking high-risk HPV DNA by ISH (p16+/DNA ISH-) in OpSCC.

2.     Compare OS of patients with p16 positive tumours demonstrating high-risk HPV DNA ISH positivity (p16+/DNA ISH+), p16+/DNA ISH- and p16 negative (p16-) OpSCC.

3.     Determine whether p16+/DNA ISH- can further be classified using RNA ISH.


Methods

Consecutive OpSCC cases from two large UK treatment centres were tested for p16 IHC. High-risk HPV DNA ISH was undertaken on all p16 positive tumours. RNA ISH was performed on a subset of p16+/ DNA ISH- cases. OS was determined from patient records and evaluated using SPSS software.


Results

There were 347 patients included in this study. The prevalence of p16+/DNA ISH- was 11.8%. Patients with p16+/ISH- OpSCC had poorer OS compared with p16+/DNA ISH+ tumours (mean OS 45.1 vs 53.2 months, p=0.001), but improved OS compared with p16- tumours (mean OS 45.1 vs 33.7 months, p=0.023). Twenty-four p16+/ISH- samples were available for RNA ISH testing, of which 15 were finally classified as HPV positive and 9 as HPV negative.


Conclusion

Patients with p16+/DNA ISH- OpSCC have poorer OS compared to those with p16+/DNA ISH+ tumours, but improved OS compared with p16- tumours. Therefore, for purposes of clinical trial stratification and prognostication, we recommend HPV DNA ISH testing on all p16+ cases. RNA ISH is a suitable test for resolving the HPV status in p16+/DNA ISH- tumours.


References

1. https://www.nice.org.uk/guidance/NG36/chapter/Recommendations#hpvrelated-disease

2. https://www.rcpath.org/resourceLibrary/g111_pharynxmucosaldataset_nov13-pdf.html