Age: 90.0
Sex: F
Vaccine: HPV4
Symptoms: Biopsy lymph gland normal, Human papilloma virus test positive, Incorrect route of product administration, Off label use
Clinical narrative: "off-label" use of quadrivalent HPV-L1 vaccine (Gardasil) for HPV-HR positive gynecological malignancies; Literature Report:  This literature marketed report was received from the authors in a published literature article titled as stated above, concerning a female patient. Initially, this patient presented with a 4 cm peri-clitoral, grade 1, squamous cell carcinoma treated by radical hemi-vulvectomy and bilateral inguinal sentinel node biopsies. The vulvectomy specimen demonstrated no lymph-vascular space invasion and the specimen's margins were clear. Bilateral inguinal sentinel lymph nodes, consisting of two nodes on the left and three nodes from right, were negative for malignant cells. No further therapy was required, and the patient never returned for follow-up until presenting 3 years later with 11 x 11 cm squamous cell carcinoma of right groin, diagnosed as with recurrent, human papillomavirus-high risk (HPV-HR) positive, squamous cell carcinoma of the vulva with metastatic disease to the right inguinal-femoral triangle (11 x 11 cm tumor) and bilateral pulmonary metastasis which was causing a right lower extremity deep vein thrombosis. A chest x-ray revealed a "snow storm" appearance from bilateral pulmonary metastasis. The patient elected to enter Hospice to help manage end-of-life care. Due to the extreme right groin and leg pain, palliative external beam radiation and low-molecular weight heparin was initiated. Radiation therapy was discontinued following 10 fractions (120 cGy to right groin/day for 10 fractions for a total dose 1200 cGy) due to increasing leg pain and tumor progression to 13 x 13 cm (20% increase). The patient requested enrollment into an immunotherapy study treating HPV-HR, intraepithelial neoplasia of the lower genital tract. The bioethics' committee convened and approved the compassionate use of the immune therapy.   On an unknown date, 7 days after palliative radiation was discontinued, the patient received the first intratumoral vaccination of quadrivalent human papillomavirus (types 6,11,16,18) recomb. vaccine (GARDASIL) 0.5 mL, using 0.25 mL of the vaccine diluted with 2.75 ml saline (total volume 3 ml) injected evenly throughout entire recurrent tumor, administered for HPV-HR positive, squamous cell carcinoma of the vulva (Off-label- use) (lot #, and expiration date were not provided); which was applied together with 5% imiquimod therapy applied immediately after intratumoral injection again on that night. From day 2 to imiquimod was applied topically to surface of tumor by the patient before bed. On day 15, the patient received the same treatment as cycle # 1. In addition, she received a subcutaneous injection in the right shoulder as a "booster". Following the second intratumoral vaccination cycle, the patient missed her 2-week follow-up appointment for her third immunotherapy cycle. Eleven weeks after her second cycle, she returned for the third and last vaccination cycle receiving received the last intratumoral injection into a 2 cm3 tumor. The third intratumoral vaccination was administered along with fourteen nights of imiquimod.  A copy of the published article is attached as further documentation of the patient's experience.   This is one of two reports from the same literature article.; Sender's Comments:  US-009507513-2201USA006060: