Analysis of Human Papilloma Virus Content and Integration in Mucoepidermoid Carcinoma

Abstract

Mucoepidermoid Carcinomas (MEC) represent the most common malignancies of salivary glands. Approximately 50% of all MEC cases are known to harbor CRTC1/3-MAML2 gene fusions, but the additional molecular drivers remain largely uncharacterized. Here, we sought to resolve controversy around the role of human papillomavirus (HPV) as a potential driver of mucoepidermoid carcinoma. Bioinformatics analysis was performed on 48 MEC transcriptomes. Subsequent targeted capture DNA sequencing was used to annotate HPV content and integration status in the host genome. HPV of any type was only identified in 1/48 (2%) of the MEC transcriptomes analyzed. Importantly, the one HPV16+ tumor expressed high levels of p16, had high expression of HPV16 oncogenes E6 and E7, and displayed a complex integration pattern that included breakpoints into 13 host genes including PIK3AP1, HIPI, OLFM4,SIRT1, ARAP2, TMEM161B-AS1, and EPS15L1 as well as 9 non-genic regions. In this cohort, HPV is a rare driver of MEC but may have a substantial etiologic role in cases that harbor the virus. Genetic mechanisms of host genome integration are similar to those observed in other head and neck cancers.

Special Issue “HPV in the Head and Neck Region 2.0”

“…Recently, we presented a Special Issue on “HPV in the head and neck region” which included several contributions to the overall knowledge of HPV in the head and neck region. In this second “Special Issue on HPV in the head and neck region 2.0”, eight original articles, one review, and one systematic review are presented [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ].…”

“…Another of the original papers examined the presence and role of HPV in 48 mucoepidermoid carcinomas (MEC) [ 2 ]. HPV was only found in 1/48 cancers, and thus it does not play a major role in this cancer either.…”

“…HPV was only found in 1/48 cancers, and thus it does not play a major role in this cancer either. This HPV-positive tumour presented high levels of HPV16 E6 and E7 RNA expression and HPV16 was integrated and affected more than 13 genes [ 2 ]. The authors concluded that HPV detection in MEC is rare.…”