Therapeutic Vaccination for Patients With HPV16+ Cervical Intraepithelial Neoplasia (CIN2/3)

Primary Objectives

- To evaluate the feasibility and toxicity of vaccination in women with CIN2/3 caused by
HPV16

- To evaluate the effect of vaccination on histology

- To compare immunogenicity of three different routes of administration: intradermal (ID),
intramuscular (IM), intralesional (IL).

Secondary Objectives:

- To evaluate changes in HPV viral load

- To evaluate the cellular immune response to vaccination

- To evaluate the humoral immune response to vaccination

- To evaluate local tissue immune response

- To correlate measures of immune response with clinical response

- To correlate measures of immune response with those observed in the preclinical model

Inclusion Criteria:

- patients with high grade cervical intraepithelial lesions (CIN2/3)

- patients whose lesions are HPV16+

- patients who are age 18 or older

- patients who are able to give informed consent

- patients who are immunocompetent

- patients who are not pregnant, committed to using adequate contraception if of
childbearing age

- patients who have a minimum hemoglobin level of 9

Exclusion Criteria:

- Patients with cytologic evidence of glandular dysplasia

- Patients with cytologic evidence of adenocarcinoma in situ

- Patients who are pregnant

- Patients with an active autoimmune disease

- Patients who are taking immunosuppressive medication

- Patients with concurrent malignancy except for nonmelanoma skin lesions

- Patients who have an allergy to gold.

- Patients with any evidence of damaged skin, or moles, scars, tattoos or marks at the
proposed site(s) of administration that might interfere with the interpretation of
local skin reactions.

- History or evidence of a physician-diagnosed chronic or recurrent inflammatory skin
disease (e.g. psoriasis, eczema, atopic dermatitis, hypersensitivity) at the proposed
site of administration in the past 5 years.

- Patients who have an active autoimmune disease or history of autoimmune disease
requiring medical treatment with systemic immunosuppressants, including: inflammatory
bowel disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis,
hemolytic anemic, or immune thrombocytopenia, rheumatoid arthritis, SLE, and Sjogren's
syndrome, sarcoidosis. Asthma or COPD that does not require systemic corticosteroids
or routine use of inhaled steroids is acceptable

- Patients who have received prior chrysotherapy (administration of gold salts to treat
rheumatoid arthritis).

- Patients with a history of arterial or venous thrombosis

- Patients with non-healed wounds.

- Patients with a history of keloid formation ( ID delivery group only)

- Patients with a history of hepatitis B with persistent infection.