Human Papillomavirus Diversity in Asian Individuals With Cutaneous Squamous Cell Carcinoma

Human papillomavirus (HPV) infection has been associated with increased risk of cutaneous squamous cell carcinoma (cSCC), particularly in immunocompromised individuals such as organ transplant recipients. However, most studies have focused on β-HPV, with limited attention to α-HPV and γ-HPV. Moreover, little is known about these associations in Asian patients, and the concordance of HPV genotypes across different tissue sites and the anatomical distribution of HPV-positive cSCC lesions remain underexplored. This study aims to address these gaps.

To characterize the spectrum and viral load of HPV genotypes across multiple tissue sites in an Asian cohort of organ transplant recipients and immunocompetent individuals.

This multicenter case-control study spanning January 2018 to December 2024 included organ transplant recipients and immunocompetent patients with cSCC residing in Singapore. Tissue samples were collected from eyebrow hair, cSCC lesions, and cutaneous warts for DNA extraction. The data analysis was conducted from June 2024 to July 2025.

The Illumina MiSeq platform was used to sequence 193 samples to determine the prevalence of α-HPV, β-HPV, and γ-HPV types in an Asian population and their anatomical distribution in patients with cSCC.

The cohort comprised 37 organ transplant recipients with cSCC and 48 immunocompetent patients with cSCC. The median (IQR) age of participants was 73.2 (67.6-81.0) years; 56 (65.9%) were male, and 29 (34.1%) were female, with 78 Chinese individuals (91.8%), 1 Malay individual (1.1%), 1 Indian individual (1.1%), and 5 (5.8%) grouped as having another race or ethnicity. Organ transplant recipients developed cSCC at a statistically significantly younger age than immunocompetent patients (median [IQR] age, 68.5 [64.0-71.0] years vs 79.5 [72.0-85.0] years, respectively), with a higher prevalence of viral warts (27 [73.0%] vs 14 [29.2%]) and greater wart body surface area involvement (median [IQR], 12% [0.5%-6.5%] vs 0% [0%-5%]). In total, 65 HPV genotypes were identified (38 β-HPV, 15 γ-HPV, 12 α-HPV). Site-specific distribution showed 56 genotypes in eyebrow hair, 30 in cSCC, and 17 in warts, with β-HPV exhibiting the greatest overlap across all 3 sites. β-HPV exhibited the highest viral loads across all tissue sites, compared to α-HPV and γ-HPV. Genotype-specific concordance between eyebrow hair and paired cSCC was low in both groups; among 55 patients, 5 (9.1%) had 1 or more concordant genotype.

In this case-control study of Asian individuals with cSCC, there were differences in the distribution of HPV genotypes in Asian organ transplant recipients and immunocompetent patients, compared to published studies. Future larger studies mapping the prevalence and types of HPV in Asia will enhance understanding of risk factors and inform targeted prevention efforts in this part of the world.