Comparison of detection methods for HPV status as a prognostic marker for loco-regional control after radiochemotherapy in patients with HNSCC.

To compare six HPV detection methods in pre-treatment FFPE tumour samples from patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who received postoperative (N = 175) or primary (N = 90) radiochemotherapy. HPV analyses included detection of (i) HPV16 E6/E7 RNA, (ii) HPV16 DNA (PCR-based arrays, A-PCR), (iii) HPV DNA (GP5+/GP6+ qPCR, (GP-PCR)), (iv) p16 (immunohistochemistry, p16 IHC), (v) combining p16 IHC and the A-PCR result and (vi) combining p16 IHC and the GP-PCR result. Differences between HPV positive and negative subgroups were evaluated for the primary endpoint loco-regional control (LRC) using Cox regression. Correlation between the HPV detection methods was high (chi-squared test, p < 0.001). While p16 IHC analysis resulted in several false positive classifications, A-PCR, GP-PCR and the combination of p16 IHC and A-PCR or GP-PCR led to results comparable to RNA analysis. In both cohorts, Cox regression analyses revealed significantly prolonged LRC for patients with HPV positive tumours irrespective of the detection method. The most stringent classification was obtained by detection of HPV16 RNA, or combining p16 IHC with A-PCR or GP-PCR. This approach revealed the lowest rate of recurrence in patients with tumours classified as HPV positive and therefore appears most suited for patient stratification in HPV-based clinical studies.

Linge A ，Schötz U ，Löck S ，Lohaus F ，von Neubeck C ，Gudziol V ，Nowak A ，Tinhofer I ，Budach V ，Sak A ，Stuschke M ，Balermpas P ，Rödel C ，Bunea H ，Grosu AL ，Abdollahi A ，Debus J ，Ganswindt U ，Lauber K ，Pigorsch S ，Combs SE ，Mönnich D ，Zips D ，Baretton GB ，Buchholz F ，Krause M ，Belka C ，Baumann M ，DKTK-ROG ... -  《-》

Molecular analyses of unselected head and neck cancer cases demonstrates that human papillomavirus transcriptional activity is positively associated with survival and prognosis.

Masterson L ，Winder DM ，Ball SL ，Vaughan K ，Lehmann M ，Scholtz LU ，Sterling JC ，Sudhoff HH ，Goon PK ... -  《BMC CANCER》

Biomarkers of HPV in head and neck squamous cell carcinoma.

Human papillomavirus (HPV) is an accepted cause of head and neck squamous cell carcinoma (HNSCC), and patients with HPV-associated HNSCC have a favorable prognosis. Currently, there is no general guidance on the most appropriate biomarkers for clinical assessment of HPV in these malignancies. We compared PCR-based and serologic HPV assays, as well as p16 immunohistochemistry, individually and in combination in a single population-based study to assess their associations with overall survival among patients with HNSCC, and thus their potential value as biomarkers. HPV16 serology was determined for 488 patients; immunohistochemical detection of p16 expression in tumors was conducted in a subset of 233 cases, and PCR-based methods to assess the presence of HPV16 DNA in a subset of 179 cases of tumors. Considering each biomarker individually in the subset of patients studied for all endpoints, seropositivity for the E6 and E7 proteins was significantly associated with enhanced all-cause survival in oropharyngeal disease [HR(E6/E7+) = 0.1, 95% confidence interval (CI) = 0.02-0.3]. Neither the presence of HPV16 DNA nor p16 immunostaining was associated with significant enhanced overall survival in oropharyngeal disease (HR(DNA) = 0.9, 95% CI = 0.3-2.9; HR(p16) = 0.3, 95% CI = 0.1-1.1). However, the combination of HPV-positive DNA and E6 or E7 serology was associated with enhanced overall survival in oropharyngeal disease (HR(DNA+/E6/E7+) = 0.1, 95% CI = 0.02-1.0), whereas E6/E7 seronegative patients with evidence of HPV in tumor DNA did not show any evidence of favorable survival (HR(DNA+/E6-/E7-) = 3.4, 95% CI = 0.6-18.1). Furthermore, patients with p16 staining and E6 or E7 seropositivity had favorable survival from oropharyngeal disease (HR(p16+/E6/E7+) = 0.1, 95% CI = 0.02-0.4), whereas patients who were p16 positive and E6/E7 seronegative had significantly increased hazard of all causes of death (HR(p16+/E6-/E7-) = 3.1, 95% CI = 1.2-7.7). A stronger association of HPV presence with prognosis (assessed by all-cause survival) is observed when "HPV-associated" HNSCC is defined using tumor status (HPV DNA status or P16) and HPV E6/E7 serology in combination rather using tumor HPV status alone.

Liang C ，Marsit CJ ，McClean MD ，Nelson HH ，Christensen BC ，Haddad RI ，Clark JR ，Wein RO ，Grillone GA ，Houseman EA ，Halec G ，Waterboer T ，Pawlita M ，Krane JF ，Kelsey KT ... -  《-》

HPV16 E6/E7 expression in circulating tumor cells in oropharyngeal squamous cell cancers: A pilot study.

Economopoulou P ，Koutsodontis G ，Avgeris M ，Strati A ，Kroupis C ，Pateras I ，Kirodimos E ，Giotakis E ，Kotsantis I ，Maragoudakis P ，Gorgoulis V ，Scorilas A ，Lianidou E ，Psyrri A ... -  《PLoS One》

Detection of human papillomavirus type 16 in oropharyngeal squamous cell carcinoma using droplet digital polymerase chain reaction.

Biron VL ，Kostiuk M ，Isaac A ，Puttagunta L ，O'Connell DA ，Harris J ，Côté DW ，Seikaly H ... -  《-》