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The frequency of high-risk human papillomavirus types, HPV16 lineages, and their relationship with p16INK4a and NF-κB expression in head and neck squamous cell carcinomas in Southwestern Iran

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Abstract

High-risk human papillomaviruses (hr-HPVs) are the key risk factors implicated in the development of a significant proportion of head and neck squamous cell carcinomas (HNSCCs). We aimed to investigate the distribution of hr-HPV types and HPV16 lineages in a sample of patients with HNSCC and the possible association between HPV status and the expression of P16INK4A and NF-κB in Iranian HNSCC patients. We examined 108 formalin-fixed, paraffin-embedded (FFPE) histologically confirmed primary SCC tissue specimens of different head and neck anatomical sites. HPV types and HPV16 lineages were determined by nested PCR and overlapping nested PCR assays, respectively, followed by gene sequencing and phylogenetic analysis. The expression of p16INK4a and NF-κB was evaluated by immunohistochemistry. Twenty-five (23.1%) HNSCC tissue specimens were tested positive for HPV infection. The most prevalent HPV type was HPV-16, followed by HPV18 and HPV11. HPV16 variants belonged to the lineage A and lineage D which were further sorted into sublineages A1, A2, and D2. A significant association between HPV status and p16INK4a immunoreactivity was observed in more than 76% of the HPV-related HNSCCs (P < 0.0001). The overexpression of p16INK4a and cytoplasmic NF-κB was more common in low-grade HNSCC tumors. Our data highlights that HPV16, in particular the A2 sublineage, followed by A1 and D2 sublineages are the major agents associated with HNSCCs in Iran. Based on HPV16 predominance and its lineage distribution pattern, it seems that the prophylactic vaccines developed for cervical cancer prevention could also be applicable for the prevention of HPV-related HNSCCs in our population.

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Acknowledgments

The authors would like to thank the staff of the Diagnostic Laboratory Sciences and Technology Research Center (DLSTRC) and Oral & Maxillofacial Pathology Laboratory, school of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.

Funding

This study was supported by a grant from Shiraz University of Medical Sciences, Shiraz, Iran, under the agreement no. 93-01-45-8241.

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Authors and Affiliations

  1. Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

    Fatemeh Pakdel, Ali Farhadi, Tahereh Pakdel & Abbas Behzad-Behbahani

  2. Department of Oral and Maxillofacial Pathology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran

    Fatemeh Pakdel

  3. Oral and Dental Disease Research Center, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran

    Azadeh Andishe-Tadbir

  4. Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

    Parnian Alavi

  5. Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohammad J. Ashraf

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Contributions

Writing—original draft preparation, methodology, and investigation: F.P. Conceptualization, methodology, writing review and editing, supervision, and visualization: A.F. Methodology and validation: T.P. Methodology and investigation: A.A.T. Project administration, software, and formal analysis: P.A. Resources and methodology: A.B.B. and M.J.A. All the authors provided a critical revision of this manuscript.

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Correspondence to Ali Farhadi.

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The authors declare that they have no competing interests.

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The Ethical Committee of Shiraz University of Medical Sciences approved this study (SUMS, ethical reference No. IR.SUMS.REC.1393.8241) given the retrospective nature of the study.

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Responsible Editor: Flavio Guimaraes Fonseca.

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Pakdel, F., Farhadi, A., Pakdel, T. et al. The frequency of high-risk human papillomavirus types, HPV16 lineages, and their relationship with p16INK4a and NF-κB expression in head and neck squamous cell carcinomas in Southwestern Iran. Braz J Microbiol 52, 195–206 (2021). https://doi.org/10.1007/s42770-020-00391-1

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