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Objectives Human papillomavirus (HPV) is a risk factor for head and neck squamous cell carcinoma (HNSCC), which is currently increasing worldwide. We evaluated the prevalence of HPV DNA and p16 expression in HNSCC patients age <45 years compared with patients aged ≥45 years. Methods Thirty-nine patients aged <45 years who presented at Besançon University Hospital with HNSCC since 2005 were included in this retrospective study. HPV DNA was detected by HPV genotyping and p16 expression was determined by immunohistochemistry using paraffin-embedded tissues. A matched-group of 38 patients aged ≥45 years from Besançon University Hospital was included. Results The overall prevalence of HPV infection was 11.7%. HPV16 was the only genotype detected in 4/39 and 5/38 patients, and p16 was expressed in 6/39 and 4/38 patients aged <45 years and ≥45 years, respectively. Conclusions HPV-positivity and p16 expression were similar in both age groups. The results suggest that p16 immunohistochemistry may provide a prognosis biomarker for all HNSCCs, not only oropharyngeal cancers, and this should be addressed in large clinical trials.

A growing body of evidence addressing the involvement of human cytomegalovirus (HCMV) in malignancies had directed attention to the oncomodulation paradigm. HCMV-DB infected human mammary epithelial cells (HMECs) in culture showed the emergence of clusters of rapidly proliferating, spheroid-shaped transformed cells named CTH (CMV-Transformed HMECs) cells. CTH cells assessment suggests a direct contribution of HCMV to oncogenesis, from key latent and lytic genes activating oncogenic pathways to fueling tumor evolution. We hypothesized that the presence of HCMV genome in CTH cells is of pivotal importance for determining its oncogenic potential. We previously reported the detection of a long non-coding (lnc) RNA4.9 gene in CTH cells. Therefore, we assessed here the presence of UL69 gene, located nearby and downstream of the lncRNA4.9 gene, in CTH cells. The HCMV UL69 gene in CTH cells was detected using polymerase chain reaction (PCR) and sequencing of UL69 gene was performed using Sanger method. The corresponding amino acid sequence was then blasted against the UL69 sequence derived from HCMV-DB genome using NCBI Protein BLAST tool. A 99% identity was present between the nucleotide sequence present in CTH cells and HCMV-DB genome. UL69 transcript was detected in RNA extracts of CTH cells, using a reverse transcription polymerase chain reaction (RT-PCR) assay, and pUL69 protein was identified in CTH lysates using western blotting. Ganciclovir-treated CTH cells showed a decrease in UL69 gene detection and cellular proliferation. In CTH cells, the knockdown of UL69 with siRNA was assessed by RT-qPCR and western blot to reveal the impact of pUL69 on HCMV replication and CTH cell proliferation. Finally, UL69 gene was detected in breast cancer biopsies. Our results indicate a close link between the UL69 gene detected in the HCMV-DB isolate used to infect HMECs, and the UL69 gene present in transformed CTH cells and tumor biopsies, further highlighting a direct role for HCMV in breast tumor development.