A Phase 0 Window of Opportunity Trial of Intratumoral Seasonal Influenza Immunization in Cutaneous Squamous Cell Carcinoma (CSCC) Patients Awaiting Curative Excision

Inclusion Criteria:

* Participants must have a diagnosis of cutaneous squamous cell carcinoma that has been biopsied and confirmed histologically. Mixed histology (such as basosquamous carcinoma, sarcomatous carcinoma) is allowed.
* Participants must have a skin tumor that measures 10 - 39 mm (not less than 10 mm and not more than 39 mm) in longest dimension by clinical exam. (Participants may have more than one untreated CSCC at the time of enrollment, but only one CSCC may be treated with the study agent.)
* Participants must be candidates for treatment (excision) by Mohs micrographic surgery.
* Age ≥18 years. Because CSCC is exceptionally rare in patients \<18 years of age, children are excluded from this study.
* ECOG performance status ≤3 (Karnofsky ≥40%, see Appendix A).
* Ability to understand and the willingness to sign a written informed consent document.
* For participants with a past medical history of Human immunodeficiency virus (HIV), they must be on effective anti-retroviral therapy with undetectable viral load measured within the 6 months prior to enrollment.
* For participants with a past medical history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* For participants with a past medical history of hepatitis C virus (HCV) infection, they must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

Exclusion Criteria:

* CSCC with the following high-risk features including peri-neural invasion of \>0.1 mm caliber, and invasion of tissue beyond the subcutaneous fat, and a diameter \> 3.9 cm.
* Evidence of in-transit/satellite, nodal, or distant metastases from CSCC, in the present or in the past medical history, including evidence from physical exam of primary site and draining lymph node basin.
* History of solid organ transplant or allogeneic bone marrow transplant.
* History of allergic reactions attributed to the seasonal flu vaccine.
* History of Guillain-Barré syndrome.
* Participants with any uncontrolled intercurrent illness, including uncontrolled cardiac disease (New York Heart Association Class III or IV heart failure, myocardial infarction in the 6 months prior to enrollment, unstable angina).
* Participants who are receiving any other investigational agents for treatment of cancer.
* Participants with a past medical history of another malignancy whose natural history or treatment is likely to interfere with the safety or efficacy assessment of the investigational regimen, according to the treating investigator.
* Participants with psychiatric illness/social situations that would limit compliance with study requirements.
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of intratumoral flu vaccine administration. Patients who do not agree to comply with these precautions are ineligible.
* Pregnant or nursing (breast-feeding) women are excluded from this study because there is an unknown but potential risk to multiple injections of flu vaccine in pregnant or nursing women.
* Note: Previous treatment with flu vaccination is not an exclusion criterion. Routine intramuscular seasonal influenza vaccination is not required nor prohibited.