Evaluate humoral and cellular immune response to administration of INO -3112 in chemo- and radiation-naïve subjects who undergo definitive surgery: a. Pre- and Post -immunotherapy tissue analysis to evaluate infiltration of T cells in the tumor. b. Evaluat e effect of number of doses on immune response s. c. Evaluat e immune response duration. 2. Evaluate humoral and cellular immune response to administration of INO-3112 in subjects after chemoradiation therapy : - Evaluat e immune response duration. 2.3 Exploratory Objectives 1. Explore anti -tumor response 2. Explore progression free survival 3 Study Design This will be a prospective, open- label, Phase I/IIa study of immunotherapy with INO -3112 in subjects with HPV -positive HNSCCa. Subjects will receive a course of treatment as described below and will be followed for safety as well as immune and clinical responses for 6 months from the last dose of immunotherapy. The safety and effects of immunotherapy will be studied in two populations: 1. In chemo - and radiation-naïve subjects who undergo definitive surgery and 2. In subjects after chemoradiation therapy. Doses of INO -3112 are based on safety experience in prior and on- going clinical trials. Based on the prior experience with these a gents, dose escalation will not be conducted in this trial. The study is divided into the following treatment cohorts: I. INO-3112 (6 mg VGX -3100 + 1 mg INO -9012) will be given to subjects before and after definitive surgery. II. INO-3112 (6mg VGX -3100 + 1 mg INO-9012) will be given to subjects after chemoradiation therapy. 3.1 General Design Study Schema: Eligible subjects will receive highly engineered plasmid DNA encoding HPV-16 and HPV-18- E6 & E7 transcription unit antigens ( VGX-3100 ) combined with the DNA encoding IL-12 (INO-9012) followed by EP with the CELLECTRA®5P device. COHORT I: Immunotherapy will be given both before and after definitive surgery. Each subject will receive a total of 4 doses of treatment, 1 -2 of them pre -surgery. Each treatment will be 6 mg 24 Date: 8 April 2016 v 2.1 INO-3112 UPCC # 39313 / Inovio HPV -005 Inovio Pharmaceuticals, Inc Clinical Protocol of VGX-3100 and 1 mg INO -9012 (INO -3112) delivered IM followed by EP. A minimum of 5 eligible subjects will be enrolled to this cohort. Pre-Surgery: 1) Subjects will be enrolled if they have confirmed HPV positive mucosal HNSCCa. Tumor tissue samples m ust be available to perform immunological correlates prior to definitive surgery. 2) After providing informed consent and being deemed eligible, subjects will receive immunotherapy. Up to 2 doses may be administered approximately once every 3 weeks (±3 days) prior to definitive surgery. 3) The number of pre -surgery immunotherapies (one vs. two injections) will be based on the estimated time interval between pre -surgery evaluation and definitive surgery. Time to surgery according to standard practice is usually 2- 4 weeks; however, this varies due to ordinary logistical considerations independent of a clinical trial. 4) Surgery will not be delayed to allow for immunotherapy. Post-Surgery: 1) Subjects will be seen approximately 2 weeks (± 7 days) post-surgery for follow up. 2) Subjects will undergo visual inspection to document healing by surgeon approximately 4 weeks post-surgery. 3) Post-surgery immunotherapy will proceed only after approval of the surgeon. 4) Subjects will receive up to 3 doses given 3 weeks (±3 days) apart. A total of 4 doses (pre - and post- surgery) will be administered. 5) Immunotherapy will be administered prior to adjuvant chemotherapy and/or radiation that may be indicated. 6) Adjuvant therapy will not be delayed for immunotherapy. 7) Subjects will be followed for tumor status as per institutional standard of care. COHORT II: Immunotherapy will start approximately 2 -6 months after completion of definitive or adjuvant chemoradiation therapy in order to allow recovery from the treatment side effects of chemoradiation . INO -3112 (6 mg of VGX-3100 and 1 mg INO -9012) will be delivered by IM injection with EP once every 3 weeks (±3 days) for a total of 4 doses. A minimum of 10 subjects will be enrolled into this cohort. 1) Subjects will be enrolled if they have HPV -16 and/or HPV- 18 positive HNSCCa confirmed by ISH or PCR, and have completed chemoradiation therapy. Adequate tissue must be available to perform immunological correlates studies. Confirmation of HPV -16 and/or HPV-18 positivity is required prior to first dose of immunotherapy. 2) Subjects will be followed for tumor status as per normal institutional standard of care. Sample Size: A minimal of 20 but no more than 25 eligible subjects will be enrolled in this study. 25 Date: 8 April 2016 v 2.1 INO-3112 UPCC # 39313 / Inovio HPV -005 Inovio Pharmaceuticals, Inc Clinical Protocol 3.2 Study Endpoints 3.2.1 Primary Endpoint The primary study endp oint is safety and tolerability based on standard laboratory and clinical adverse event monitoring: 1. Adverse events will be measured and graded according to “Common Terminology Criteria for Adverse Events (CTCAE)”, NCI version 4.03 issued by the US Department of Health and Human Services.