Via Research Recognition Day 2024 VCOM-Carolinas

Clinical Case-Based Reports

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Introduction

Discussion

Results

The vaccine has shown promise in chemoprevention and treatment over the past decade, reducing the development of new NMSCs and showing curative potential for basaloid SCC and invasive SCC. 1, 3, 4 Furthermore, studies have shown a reduction of actinic keratoses (AK), a precursor to SCC, following 9-valent HPV vaccine administration. 5 NMSCs are more common among immunocompromised individuals. A case of a renal transplant recipient, who received the 9-valent HPV vaccine, was cured of SCC in situ nine months after the first injection. 6 The presence of HPV DNA in NMSC and AK has been confirmed in studies. In 2005, a study showed a significantly higher viral load in AK compared to SCC, implying HPV's possible role in the early stages of carcinogenesis. 7 Recent research by Strickley et al. suggests that HPV might play a protective role against skin cancer development, highlighting the importance of adaptive immunity in response to commensal β -HPV. It was observed that NMSC thrived when antiviral immunity was compromised, mimicking immunosuppression. These findings suggest a promising approach for future vaccine efforts to boost immunity against commensal β -HPV via T lymphocytes. 8 Although the HPV vaccine targets ɑ -HPV serotypes, and NMSC has been associated with β -HPV, the success in NMSC prevention and treatment cannot be overlooked. The possibility of cross-reactivity between serotypes has been proposed but still requires validation. 9 Besides NMSC, the HPV vaccination has also been used, in combination with radiation and topical chemotherapy, to cure gynecological malignancy. These treatment modalities may work synergistically to facilitate antigen processing and improve local immune responses. 10 Despite the promising outcomes and findings presented, limitations do exist. While evidence points towards a beneficial role of the HPV vaccine, most data come from case reports and case series, which inherently lack the control of randomized controlled trials. Additionally, the hypothesized cross-reactivity between ɑ - HPV and β -HPV serotypes needs further investigation. The findings from this case report should be viewed as a promising preliminary step towards a shifting approach to NMSC management. Larger-scale clinical trials are needed to validate the effectiveness of the HPV vaccine in NMSC and explore its exact mechanism of action. Such research could potentially lead to a cost-effective, accessible, and innovative strategies for preventing and treating NMSC. Ultimately, there could be a benefit to a broad range of patients with potential to alleviate the current burden which exists in our healthcare systems. This study emphasizes the need for continued research, increased awareness, and targeted funding to explore this potentially transformative therapeutic strategy fully.

Nonmelanoma skin cancer (NMSC), including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), ranks among the world's most common cancer. Studies have shown the presence of human papillomavirus (HPV) DNA in NMSC. 1 While surgery remains the standard of care for NMSC, not all patients are ideal surgical candidates. Moreover, one NMSC diagnosis increases the risk for subsequent diagnosis and the need for additional surgeries. 2 It is important to develop alternative treatments for NMSC. This case demonstrates clinical improvement of several NMSCs after being given the HPV vaccine. In 2010, an immunocompetent 88-year-old male presented at our private dermatology practice with numerous suspected cancerous skin lesions. Over five years, he had 23 confirmed NMSCs. Considering this patient’s age, extensive disease, and our previous experience in using the vaccine to prevent and treat NMSC, he consented to receive an intramuscular (IM) injection of the quadrivalent HPV vaccine in November 2014. Encouraged by the reduction of several lesions post-vaccination, the patient received an additional IM injection of the quadrivalent HPV vaccine followed by three IM injections of the 9-valent HPV vaccine at subsequent visits in 2015. The pictures show the regression of his skin lesions throughout 2015. In January 2016, he received his first intralesional (IL) dose of the 9-valent HPV vaccine, after which his skin lesions continued to regress until his death from unrelated causes in 2016. Case Report

References 1. Nichols AJ, Gonzalez A, Clark ES, Khan WN, Rosen AC, Guzman W, Rabinovitz H, Badiavas EV, Kirsner RS, Ioannides T. Combined Systemic and Intratumoral Administration of Human Papillomavirus Vaccine to Treat Multiple Cutaneous Basaloid Squamous Cell Carcinomas. JAMA Dermatol. 2018 Aug 1;154(8):927-930. doi: 10.1001/jamadermatol.2018.1748. PMID: 29971321; PMCID: PMC6143030. 2. Marcil I, Stern RS. Risk of Developing a Subsequent Nonmelanoma Skin Cancer in Patients With a History of Nonmelanoma Skin Cancer: A Critical Review of the Literature and Meta-analysis. Arch Dermatol. 2000;136(12):1524 – 1530. doi:10.1001/archderm.136.12.1524 3. Nichols AJ, Allen AH, Shareef S, Badiavas EV, Kirsner RS, Ioannides T. Association of Human Papillomavirus Vaccine With the Development of Keratinocyte Carcinomas. JAMA Dermatol. 2017 Jun 1;153(6):571-574. doi: 10.1001/jamadermatol.2016.5703. PMID: 28196178; PMCID: PMC5540031. 4. Geizhals, S., & Lebwohl, M. G. (2020). The Successful Treatment of Multiple Cutaneous Malignancies with HPV Vaccination: Case Report. SKIN The Journal of Cutaneous Medicine , 4 (2), 148 – 151. https://doi.org/10.25251/skin.4.2.9 5. Wenande E, Bech-Thomsen N, Togsverd-Bo K, Haedersdal M. Off-Label 9-Valent Human Papillomavirus Vaccination for Actinic Keratosis: A Case Series. Case Rep Dermatol. 2021 Sep 15;13(3):457 463. doi: 10.1159/000518666. PMID: 34720918; PMCID: PMC8525264. 6. Nichols AJ, De Bedout V, Fayne RA, Burke GW, Kirsner RS, Ioannides T. Systemic and intratumoral 9-valent human papillomavirus vaccine treatment for squamous cell carcinoma in situ in a renal transplant recipient. JAAD Case Rep. 2020 Mar 25;6(4):289291. doi: 10.1016/j.jdcr.2020.02.002. PMID: 32258300; PMCID: PMC7109374. 7. Weissenborn SJ, Nindl I, Purdie K, Harwood C, Proby C, Breuer J, Majewski S, Pfister H, Wieland U. Human papillomavirus-DNA loads in actinic keratoses exceed those in non-melanoma skin cancers. J Invest Dermatol. 2005 Jul;125(1):93-7. doi: 10.1111/j.0022-202X.2005.23733.x. PMID: 15982308. 8. J.D. Strickley, J.L. Messerschmidt, M.E. Awad, T. Li, T. Hasegawa, D.T. Ha, et al., Immunity to commensal papillomaviruses protects against skin cancer, Nature (2019), https://doi.org/10.1038/s41586 019-1719-9. 9. Gupta R, Rady PL, Doan HQ, Tyring SK. Development of a β -HPV vaccine: Updates on an emerging frontier of skin cancer prevention. J Clin Virol. 2020 May;126:104348. doi: 10.1016/j.jcv.2020.104348. Epub 2020 Apr 4. PMID: 32334327. 10. Reedy M, Jonnalagadda S, Palle K. Case Report: Intra-Tumoral Vaccinations of Quadrivalent HPV-L1 Peptide Vaccine With Topical TLR-7 Agonist Following Recurrence: Complete Resolution of HPV HR-Associated Gynecologic Squamous Cell Carcinomas in Two Patients. Pathol Oncol Res. 2021 Dec 20;27:1609922. doi: 10.3389/pore.2021.1609922. PMID: 34987310; PMCID: PMC8720759.

For the completion of this project, I would like to thank and remember the patient who made this report possible and to the staff at Treasure Cost Dermatology for caring for the patient. I would also like to thank the staff at Treasure Coast Dermatology for helping organize the patient information. Lastly, I would like to thank Dr. Romero-Masters for his scientific expertise on virus physiology.

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2024 Research Recognition Day