Evaluation of human papillomavirus testing for squamous cell carcinoma of the tonsil in clinical practice

Abstract

The current study suggests that using a combination of p16 IHC/HPV ISH/HPV PCR, in a three-tiered, staged algorithm, in conjunction with consensus reporting of HPV ISH, leads to less equivocal molecular classification. In order to ensure consistent reporting of this emerging disease, it is increasingly important for the head-and-neck oncology community to define the minimum requirements for assigning a diagnosis of 'HPV-related' oropharyngeal SCC in order to inform prognosis and for stratification in clinical trials.

P16INK4A immunostaining is a strong indicator for high‐risk‐HPV‐associated oropharyngeal carcinomas and dysplasias, but is unreliable to predict low‐risk‐HPV‐infection in head and neck papillomas and laryngeal dysplasias

“…5,13,14,18,[20][21][22] Recent studies even suggest to use 70% immunopositivity of the carcinoma tissue as a cut-off point. 4,11,12 In our study, we indeed observed the strong and block positive p16 INK4A immunostaining in all except one HPV16-positive OPSCC. Despite the fact that a small fraction of the HPV-negative OPSCC did show p16 INK4A positivity, the correlation of this surrogate marker with HPV16-presence is highly significant.…”

p16 Immunohistochemistry As a Standalone Test for Risk Stratification in Oropharyngeal Squamous Cell Carcinoma

“…There are a few different monoclonal antibody clones available for use. The most commonly utilized is clone E6H4 (MTM Laboratories; Heidelberg, Germany) [2,5,10,11], followed by other less commonly utilized clones such as 16P04 (Neo Markers; Fremont, CA) [3], and JC8 (Santa Cruz Biotechnology Inc., Santa Cruz, CA) [27]. While there has been no formal study comparing their use, studies utilizing all of these different antibodies have shown strong predictive value for their staining results [2,3,5,27].…”

“…Many advocate p16 IHC as a screening test which, when positive, is to be followed by an HPV specific test such as DNA ISH, PCR, or both [1,7,10,11]. There is an emerging view in oropharyngeal SCC, however, that the high correlation with detectable HPV RNA [9] and the strong risk stratification for patient survival provided by p16 IHC make it a suitable single marker for defining a patient's tumor as biologically and clinically favorable for treatment and counseling.…”

“…Most of the studies are retrospective, but several prospective studies have been performed and analyzed as well [2,3,5,9,12]. There is very high correlation between the HPVspecific tests (of all types) [7,9] and also between p16 immunohistochemistry and HPV-specific testing, particularly with the newer HPV RNA tests (Table 1) [2,3,5,[8][9][10][11][13][14][15]. In a pooled analysis by Robinson et al [1] of 496 patients from several studies utilizing DNA-based HPV testing, the authors reported that only 5% of cases were p16 positive/HPV negative and that 8% were p16 negative/HPV positive.…”

“…It is widely discussed that there should be a ''gold standard'' for testing, and that this gold standard should be the presence of high risk HPV E6/E7 mRNA [7,10]. While this is an attractive and popular concept, when it comes to patient risk stratification, it is somewhat misleading.…”