Sex: M
Vaccine: HPV9
Symptoms: Biopsy conjunctiva abnormal, Computerised tomogram, Malignant neoplasm of conjunctiva, Off label use, Slit-lamp examination
Clinical narrative: off label use / Papillomatous OSSN treated with IM HPV 9-valent vaccine; Literature Report.  Information has been received from the authors in a published literature article (title as above), referring to 79-year-old man, who was referred to the ocular surface oncology clinic for evaluation of a recurrent conjunctival lesion in the left eye. He had a history of significant sun exposure as well as 2 previous conjunctival lesions in the left eye that were both treated surgically. Pathology revealed carcinoma in situ (carcinomatous intraepithelial squamous neoplasia III/III) with positive margins. The new conjunctival lesion was first noticed on an unknown date, 3 months before and had been treated with a 3-week course of topical interferon alfa-2b by his referring provider with no improvement.   On an unknown date, on presentation, the visual acuity was 20/25 in the right eye and 20/200 in the left eye. The patient underwent a corneal and conjunctival incisional biopsy at our institution which revealed conjunctival squamous cell carcinoma (SCCA), p16 positivity, and staining positive for highrisk HPV. Given the diffuse nature of this recurrent lesion, he was counseled that SCCA likely required additional surgical intervention, but the patient refused. Given the patient's previous failed medical and surgical treatment history and the papillomatous morphology of the lesion, off-label use of the hpv rl1 6 11 16 18 31 33 45 52 58 vlp vaccine (yeast) (GARDASIL 9) vaccine for therapeutic use was discussed and the patient consented to its administration.   On unknown dates, the patient received the intramuscular hpv rl1 6 11 16 18 31 33 45 52 58 vlp vaccine (yeast) (GARDASIL 9)  as an off-label therapeutic regimen at the 6-week interval and followed by slitlamp examination and High-resolution ocular computed tomography (HROCT). On completion of 3 doses of hpv rl1 6 11 16 18 31 33 45 52 58 vlp vaccine (yeast) (GARDASIL 9) vaccine, dramatic reduction in lesion size was noted on slitlamp examination. In addition, reduced epithelial thickening and hyperreflectivity was noted. The patient did not experience any adverse effects secondary to vaccine use. After a fourth hpv rl1 6 11 16 18 31 33 45 52 58 vlp vaccine (yeast) (GARDASIL 9) vaccine dose, a small area of tumor persisted, and surgical removal was discussed for the residual disease, which he again refused.  The patient agreed to treatment with topical 1% 5-fluorouracilo eye drops. On follow-up 3 months later, the patient had completed 3 cycles and demonstrated improvement, although there was still some residual tumor. He completed 3 more cycles of 1% 5-FU topical eye drops which further debulked the tumor but did not achieve complete resolution. The patient was switched to mitomycin C  (MMC) 0.04% topical therapy, and the patient completed 2 cycles, accompanied by prednisolone acetate 1% drops twice a day as needed. The lesion continued to improve, but the patient experienced significant pain and photophobia from the MMC drops, refusing any further topical drop therapy, 3 additional doses of the intramuscular hpv rl1 6 11 16 18 31 33 45 52 58 vlp vaccine (yeast) (GARDASIL 9) vaccine were thus administered, with the aim of treating the residual lesion, with no response.   Unfortunately, 3 months after the last intramuscular hpv rl1 6 11 16 18 31 33 45 52 58 vlp vaccine (yeast) (GARDASIL 9) vaccine and 5 months off all topical therapy, the lesion enlarged with corneal involvement. After extensive discussion, the patient refused any further treatment and opted for observation. There continued to be no clinical signs of orbital or lymph node involvement.  A copy of the published article is attached as further documentation of the patient's experience.  Lot number is being requested and will be submitted if received.