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. 2022 Mar 21;13(1):18.
doi: 10.1007/s12672-022-00475-4.

Mapping human papillomavirus, Epstein-Barr virus, cytomegalovirus, adenovirus, and p16 in laryngeal cancer

Alexandra Schindele  1 , Anna Holm  2 , Karin Nylander  3 , Annika Allard  4 , Katarina Olofsson  5
Affiliations

Mapping human papillomavirus, Epstein-Barr virus, cytomegalovirus, adenovirus, and p16 in laryngeal cancer

Alexandra Schindele et al. Discov Oncol. .

Abstract

Purpose: Apart from tobacco and alcohol, viral infections are proposed as risk factors for laryngeal cancer. The occurrence of oncogenic viruses including human papilloma virus (HPV) and Epstein-Barr virus (EBV), in laryngeal squamous cell carcinoma (LSCC) varies in the world. Carcinogenesis is a multi-step process, and the role of viruses in LSCC progression has not been clarified. We aimed to analyze the presence and co-expression of HPV, EBV, human cytomegalovirus (HCMV) and human adenovirus (HAdV) in LSCC. We also investigated if p16 can act as surrogate marker for HPV in LSCC.

Methods: Combined PCR/microarrays (PapilloCheck®) were used for detection and genotyping of HPV DNA, real-time PCR for EBV, HCMV and HAdV DNA detection, and EBER in situ hybridization (EBER-ISH) for EBV detection in tissue from 78 LSCC patients. Additionally, we analyzed p16 expression with immunohistochemistry.

Results: Thirty-three percent (26/78) of LSCC tumor samples were EBV positive, 9% (7/78) HCMV positive and 4% (3/78) HAdV positive. Due to DNA fragmentation, 45 samples could not be analyzed with PapilloCheck®; 9% of the remaining (3/33) were high-risk HPV16 positive and also over-expressed p16. A total of 14% (11/78) of the samples over-expressed p16.

Conclusion: These findings present a mapping of HPV, EBV, HCMV and HAdV, including the HPV surrogate marker p16, in LSCC in this cohort. Except for EBV, which was detected in a third of the samples, data show viral infection to be uncommon, and that p16 does not appear to be a specific surrogate marker for high-risk HPV infection in LSCC.

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Conflict of interest statement

The authors report no conflicts of interest.

Figures

Fig. 1
Fig. 1
Flowchart of LSCC samples for virus and p16 analysis
Fig. 2
Fig. 2
EBV, HCMV, HAdV in analyzed in 78 LSCC samples. HPV analyzed in subgroup with 33 samples, all samples were high-risk HPV16 positive. Results presented in percentage of positive samples
Fig. 3
Fig. 3
Viral co-infections in LSCC samples. Results presented in percentage of positive samples. None of the patients had infection with more than two viruses simultaneously
Fig. 4
Fig. 4
EBER in situ hybridization (EBER-ISH) applied for EBV mapping in tumor and connective tissue of a LSCC sample. Signals are detected as purple stained cells. EBER positive cells in tumor (black arrow) and connective tissue (white arrow)
Fig. 5
Fig. 5
Representative p16 immunohistochemistry (IHC) staining in a LSCC sample with high Quickscore = 18 (proportion: 6 × intensity: 3)
Fig. 6
Fig. 6
p16 Quickscore ranking groups presented in percentage
See this image and copyright information in PMC

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