Prevalence and type distribution of human papillomavirus infections in Danish patients diagnosed with vulvar squamous cell tumors and precursors

Annemarie Brusen Villadsen; Caspar Bundgaard-Nielsen; Lea Ambühl; Majbritt Tang Svendsen; Inge Søkilde Pedersen; Estrid Stæhr Hansen; Ulrik Baandrup; Jan Blaakær; Suzette Sørensen

doi:10.1016/j.gore.2021.100828

Prevalence and type distribution of human papillomavirus infections in Danish patients diagnosed with vulvar squamous cell tumors and precursors

Gynecol Oncol Rep. 2021 Jul 5:37:100828. doi: 10.1016/j.gore.2021.100828. eCollection 2021 Aug.

Authors

Annemarie Brusen Villadsen^{1

2}, Caspar Bundgaard-Nielsen^{1

2}, Lea Ambühl^{1

2}, Majbritt Tang Svendsen^{1

2}, Inge Søkilde Pedersen^{2

3

4}, Estrid Stæhr Hansen⁵, Ulrik Baandrup^{1

2}, Jan Blaakær^{6

7}, Suzette Sørensen^{1

2}

Affiliations

¹ Centre for Clinical Research, North Denmark Regional Hospital, Hjørring, Denmark.
² Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
³ Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark.
⁴ Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
⁵ Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
⁶ Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark.
⁷ Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

Abstract

Objective: To study the prevalence and type distribution of human papillomavirus (HPV) in patients with vulvar high-grade precancerous lesions and vulvar squamous cell carcinoma (VSCC).

Methods: Formalin-fixed and paraffin-embedded (FFPE) tissue samples from Danish patients diagnosed with vulvar precancerous lesions or VSCC in the period from 2010 to 2012 were obtained. HPV-DNA detection was carried out by the use of polymerase chain reaction (PCR) using GP5+/GP6+ primers and genotyped by sequencing. A systematic literature search on the PubMed database was performed to investigate the prevalence and genotype distribution worldwide.

Results: In the present study population (n = 149) 52 vulvar high-grade squamous intraepithelial lesions (HSIL), 2 differentiated vulvar intraepithelial neoplasia (dVIN), and 95 VSCC cases were identified. HPV was detected in 85 patients (57.0%). Overall, a higher proportion of the vulvar high-grade precancerous lesions were HPV positive compared to VSCC (83.6% vs. 42.1%, p < 0.001). Additionally, HSIL had a significantly higher HPV-positive rate compared to keratinizing VSCC (84.6% vs. 33.3%, p < 0.001). However, the HPV positivity was comparable between HSIL and non-keratinizing VSCC (84.6% vs. 82.4%, p = 0.825). One dVIN was HPV positive whereas the other was HPV negative. HPV-16 was the most common HPV type (68.2%), followed by HPV-33 (18.8%) and HPV-18 (8.2%).

Conclusions: Most vulvar HSIL and non-keratinizing VSCCs appear to be HPV associated. However, we find a high HPV association in keratinizing VSCC, which needs to be further studied. HPV-16 remains the predominant genotype, but HPV-33 also seems to play a role in the development of VSCC.

Keywords: HPV-16; HPV-33; Human papillomavirus; Vulvar high-grade squamous intraepithelial lesions; Vulvar intraepithelial neoplasia; Vulvar squamous cell carcinoma.