High-risk human papillomavirus in oral cavity squamous cell carcinoma

Abstract

21Purpose: The prevalence of human papillomavirus (HPV) in oral cavity squamous cell carcinoma 22 (OSCC) varies significantly based on assay sensitivity and patient geography. Accurate detection is 23 essential to understand the role of HPV in disease prognosis and management of patients with 24 OSCC. 25Methods: We generated and integrated data from multiple analytes (HPV DNA, HPV RNA, and 26 p16), assays (immunohistochemistry, PCR, qPCR and digital PCR) and molecular changes (somatic 27 mutations and DNA methylation) from 153 OSCC patients to correlate p16 expression, HPV DNA, 28 and HPV RNA with HPV incidence and patient survival. 29Results: High prevalence (33-58%) of HPV16/18 DNA did not correlate with the presence of 30 transcriptionally active viral genomes (15%) in tumors. Eighteen percent of the tumors were p16 31 positive. and only 6% were both HPV DNA and RNA positive. Most tumors with relatively high-32 copy HPV DNA, and/or HPV RNA, but not with HPV DNA alone (irrespective of copy number), 33were wild-type for TP53 and CASP8 genes. In our study, p16 protein, HPV DNA and HPV RNA, 34 either alone or in combinations, did not correlate with patient survival. Nine HPV-associated genes 35 stratified the virus +ve from the -ve tumor group with high confidence (p<0.008) when HPV DNA 36 copy number and/or HPV RNA were considered to define HPV positivity and not HPV DNA alone 37 irrespective of their copy number (p < 0.2). 38Conclusions: In OSCC, the presence of both HPV RNA and p16 are rare. HPV DNA alone is not an 39 accurate measure of HPV positivity and therefore not informative. Moreover, HPV DNA, RNA or 40 p16 don't correlate with outcome. 41 42

Prevalence of human papillomavirus16 DNA and p16INK4a protein in oral squamous cell carcinoma: A systematic review and meta-analysis

“…[ 17 ] and Palve et al . [ 18 ] detected the presence of E6 transcript by SYBR Green-based qPCR assay. On the other hand, the transcripts E6/E7 were detected by consensus PCR in the study conducted by Shima et al .…”

“…[ 26 ] Thus, mRNA profiling can be performed along with the detection of DNA for early and confirmatory detection of HPV infection. [ 18 26 ] However, its use as a biomarker in the diagnosis of OSCC is contradictory due to its instability as compared to DNA and protein. RNA can also be silenced by host defense mechanism and hence may not lead to the development of cancer.…”

Diagnostic and prognostic impact of E6/E7 mRNA compared to HPV DNA and p16 expression in head and neck cancers: an Egyptian study

“…In this research, two of the DNA-positive samples did not show HPV16 viral transcripts. Correspondingly, a study by Palve et al [50] demonstrated that only 15% of tumors that were HPV DNApositive had E6/E7 mRNA expressed. This could mirror a transient infection irrelevant to carcinogenesis [41,42,51].…”