Therapeutic Response to Treatment of a Papillomatous Ocular Surface Squamous Neoplasia With Intramuscular Human Papillomavirus Vaccine.

PURPOSE: The purpose of this study was to describe the response of a papillomatous ocular surface squamous neoplasia (OSSN) to the intramuscular (IM) 9-valent human papillomavirus (HPV) vaccine after failed medical and surgical interventions. METHODS: A 79-year-old White man with a conjunctival lesion underwent a biopsy which revealed OSSN and positivity for high-risk HPV. Initially treated with medical therapy and surgical excisions, the patient developed a recurrence and refused further surgery. He was given 4 doses of IM HPV vaccine at the 6-week interval. RESULTS: A dramatic reduction in lesion size and reduced epithelial thickening and hyperreflectivity was noted on slitlamp examination and high-resolution anterior segment optical coherence tomography after receiving the IM HPV vaccine. Although lesion size was markedly reduced, the therapy did not achieve total resolution, resulting in further treatment with topical 1% 5-fluorouracil (5-FU) eye drops and later 0.04% mitomycin C eye drops. The patient then elected to discontinue further treatment and solely observe. CONCLUSIONS: This case report adds to the growing literature demonstrating the potential therapeutic use of vaccines in cancer treatment. Although HPV vaccination is currently approved for prophylaxis, the use of HPV vaccines as a therapeutic option for various HPV-mediated diseases, including OSSN, should be further explored. The HPV vaccine yielded significant initial improvement in this patient who refused further surgical interventions. The use of IM HPV vaccine as an adjunctive treatment of papillomatous OSSN may represent a potential therapeutic option in cases refractory to standard treatment modalities.

Keratinocyte Carcinomas in Immunocompromised Patients Are Reduced After Administration of the Nonavalent Human Papillomavirus Vaccine.

Immunosuppression, as seen in solid organ transplant recipients, is highly associated with the development of keratinocyte carcinomas (KCs). Reducing the level of immunosuppression lowers the incidence of KCs but at the cost of increased potential morbidity and mortality. Recent studies have revealed a greater prevalence of HPV DNA, especially that of β-HPV, in KCs of immunocompromised patients compared to KCs of immunocompetent individuals. A prior report demonstrated that the HPV vaccine was associated with reducing KC incidence in immunocompetent patients. The nonavalent HPV vaccine was administered to two immunosuppressed individuals with histories of multiple prior KCs. Both patients are male, with Patient 1 being a liver transplant recipient who was on tacrolimus for an extended period and Patient 2 having Crohn’s disease and currently being treated with mercaptopurine. The treatment was well tolerated without adverse events and was associated with dramatic reductions in average incidence of KCs/year in both patients. Patient 1 demonstrated an 88% reduction in new KCs/year (87% squamous cell carcinomas (SCCs); 100% basal cell carcinomas (BCCs) post-injection of the intramuscular vaccine and Patient 2 demonstrated a 63% reduction in incidence of KCs/year (30% SCCs; 100% BCCs). Evidence links the β-HPV genera to the development of SCCs and actinic keratoses. The nonavalent HPV vaccine, containing antigens of the α-HPV genera, may also induce humoral immunity to β-HPV due to shared expression of L1 and L2 capsid proteins. The HPV vaccine may be an effective tool in the prevention of KCs in immunosuppressed patients. J Drugs Dermatol. 2022;21(5):526-528. doi:10.36849/JDD.6536.

Combined Systemic and Intratumoral Administration of Human Papillomavirus Vaccine to Treat Multiple Cutaneous Basaloid Squamous Cell Carcinomas.

Importance: Squamous cell carcinoma (SCC) is the second most common form of skin cancer, and its incidence is increasing. When surgical management is not an option, finding a safe and efficacious treatment is a challenge. Mounting evidence suggests that the human papillomavirus (HPV) is involved in the pathogenesis of some SCCs. Objective: To assess whether the 9-valent HPV vaccine could be an effective treatment strategy for cutaneous SCC. Design, Setting, and Participants: A woman in her 90s with multiple, inoperable cutaneous basaloid SCCs was successfully treated at a university-based outpatient dermatology clinic with a combination of systemic and intratumoral delivery of the 9-valent HPV vaccine from March 17, 2016, through February 27, 2017, and then followed up through May 21, 2018. Main Outcomes and Measures: Reduction in tumor size and number after a combination of systemic and intratumoral administration of the HPV vaccine. Results: All tumors resolved 11 months after the first intratumoral injection of the vaccine. The patient remained free of tumors at the end of follow-up. Conclusions and Relevance: This is the first report, to our knowledge, of complete regression of a cutaneous malignant tumor after combined systemic and direct intratumoral injection of the 9-valent HPV vaccine. This report suggests that the HPV vaccine may have therapeutic utility for SCCs in patients who are poor surgical candidates, have multiple lesions, or defer surgery.

Association of Human Papillomavirus Vaccine With the Development of Keratinocyte Carcinomas.

Importance: Keratinocyte carcinomas (KCs), consisting of squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs), are the most common human malignant neoplasms. Several risk factors have been implicated in KC development. For some SCCs, particularly those in immunocompromised patients, human papillomavirus (HPV) may be an important factor. Objective: To determine whether quadrivalent HPV vaccination would affect the development of KCs in immunocompetent patients with a history of multiple KCs. Design, Setting, and Participants: Two patients with a history of multiple KCs-a man in his 70s (patient 1) and a woman in her 80s (patient 2)-were treated in a private dermatology practice. Each patient received 3 doses of the quadrivalent HPV vaccine at 0, 2, and 6 months in 2013, and both patients underwent full-body skin examinations at least every 3 months. Biopsy-proven skin cancers were recorded for 16 months (for patient 1) or 13 months (for patient 2) after the first dose of vaccine and then compared with the number of biopsy-proven skin cancers recorded over a similar period before the first dose of vaccine. The period of observation was from October 18, 2011, to June 21, 2014. Main Outcomes and Measures: The numbers of new SCCs and BCCs after the first dose of the quadrivalent HPV vaccine. Results: Patient 1 had a mean of 12 new SCCs and 2.25 new BCCs per year before vaccination. After vaccination, he developed 4.44 SCCs and 0 BCCs per year, a 62.5% reduction in SCCs and a 100% reduction in BCCs. Patient 2 had a mean of 5.5 new SCCs and 0.92 new BCCs per year before vaccination. After vaccination, she developed 1.84 SCCs and 0 BCCs per year, a 66.5% reduction in SCCs and a 100% reduction in BCCs. The quadrivalent HPV vaccine was well tolerated by both patients and had no adverse effects. Conclusions and Relevance: A reduction of SCCs and BCCs was observed in 2 patients after administration of the quadrivalent HPV vaccine. These findings highlight the possibility that cutaneous SCC development, and perhaps BCC development, may be driven in part by HPV in immunocompetent patients. Human papillomavirus vaccination may represent an efficacious, cost-effective, readily available, and well-tolerated strategy for preventing KCs.