Combination of UCPVax Vaccine and Atezolizumab for the Treatment of Human Papillomavirus Positive Cancers (VolATIL)

Inclusion Criteria: 1. Signed informed consent 2. Histologically confirmed HPV+ cancers, defined by p16+ (IHC) or HPV genotyping, corresponding to one of the following selected squamous cell carcinoma types: * Anal cancer * Head and Neck carcinoma, * cervical and vulvar carcinoma 3. Locally advanced or metastatic disease 4. Pre-treated with at least 1 line of anticancer standard treatment (chemotherapy, radiochemotherapy or targeted therapy…) 5. Age ≥ 18 and ≤ 75 years old 6. Measurable disease defined according to iRECIST v1.1 guidelines (Note: Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.) 7. Patients must have a mandatory treatment-free interval of at least 21 days following previous systemic anti-cancer treatments 8. Patients who have received previous systemic anticancer treatment and/or radiotherapy should have recovered from any treatment related toxicity, to a level of ≤ grade 1 (according to National Cancer Institute \[NCI\] common terminology criteria for adverse events, version 5 (CTCAE v5) with the exception of Grade 2 alopecia 9. Performance status \< 2 (Annex 3) 10. Availability of a pre-treatment tumor sample (archival FFPE \[formalin-fixed paraffin-embedded\] block) and presence of a tumor lesion suitable for a biopsy 11. Patient affiliated to or beneficiary of French social security system 12. Ability to comply with the study protocol, in the Investigator's judgment. Exclusion Criteria: Non-eligible to a clinical trial: 1. Patients previously exposed to anti-tumor immunotherapy as anti-PD-1, anti-PD-L1, or anti-CTLA4 agent or any immune therapy. (HPV vaccination is allowed) 2. Diagnosis of additional malignancy within 3 years prior to the inclusion with the exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical or breast cancer 3. Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study 4. Current participation in a study of an investigational agent or in the period of exclusion 5. Pregnancy, breast-feeding or absence/refusal of adequate contraception for fertile patients during the period of treatment and for 6 months from the last treatment administration 6. Patient under guardianship, curatorship or under the protection of justice Cancer-specific exclusion criteria: 7. Uncontrolled pleural effusion, pericardial effusion, ascites or symptomatic fistula 8. Uncontrolled tumor-related pain: exposing patients to risk of exposure to corticoids or iterative hospitalizations. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to randomization. Patients should be recovered from the effects of radiation. There is no required minimum recovery period 9. Known active central nervous system metastases and/or carcinomatous meningitis. Subject with previously treated brain metastases and with radiological and clinical stability are allowed Non-eligible to treatment: 10. Inadequate organ functions: known cardiac failure of unstable coronaropathy, respiratory failure, or uncontrolled infection or another life-risk condition 11. Active or chronic hepatitis B or C and/or HIV positive (HIV 1/2 antibodies patients), or a known history of active Tuberculosis bacillus 12. Any immunosuppressive therapy (i.e. corticosteroids \>10mg of hydrocortisone or equivalent dose) within 14 days before the planned start of study therapy 13. Active autoimmune disease that has required a systemic treatment in past 2 years (i.e. corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin) is allowed Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, (see Annex 5 for a more comprehensive list of autoimmune diseases and immune deficiencies) with the following exceptions: * Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study, * Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study, * Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: 1. Rash must cover \< 10% of body surface area, 2. Disease is well controlled at baseline and requires only low-potency topical corticosteroids, 3. No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months, 14. Prior allogeneic bone marrow transplantation or prior solid organ transplantation 15. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 16. Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of atezolizumab formulation 17. History of idiopathic or secondary pulmonary fibrosis (History of radiation pneumonitis in the radiation field fibrosis is permitted), or evidence of active pneumonitis requiring a systemic treatment with 28 days before the planned start of study therapy 18. Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study 19. Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia 20. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study 21. Patients under chronic treatment with systemic corticoids or other immunosuppressive drugs (prednisone or prednisolone ≤ 10 mg/day is allowed) for a period of at least 4 weeks and whose treatment was not stopped 1 week prior to the start of the study treatment 22. Patient with intra-alveolar hemorrhage, pulmonary fibrosis, or uncontrolled asthma, or chronic obstructive disease (COPD), defined as at least 1 hospitalization within 4 months prior to enrollment or as at least 3 exacerbations during the last year prior to enrollment 23. Patients requiring oxygen therapy 24. Patients with LEVF (Left Ejection Ventricular Fraction) \<40% 25. Hospitalization for cardiovascular or pulmonary disease within 4 weeks prior to enrollment. 26. Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study Note: Patients must agree not to receive live, attenuated influenza vaccine (e.g.,FluMist®) within 28 days prior to randomisation, during treatment or within 5 months following the last dose of atezolizumab 27. Inadequate hematology function: Lymphocyte count at baseline \< 800/mm3 ; neutrophil count \<1500/mm3, platelets \<100000/mm3, Hemoglobin\<9g/dL 28. Inadequate hepatic function: bilirubin 2.5 fold ULN (upper limit of normal), AST/ALT (ASpartate Transaminase /ALanine Transaminase) 2.5 fold ULN or 5 fold ULN with liver metastasis, International normalized thromboplastin time ratio \>1.5 29. Inadequate renal function: MDRD (Modification of Diet in Renal Disease ) CrCl (Creatinine Clearance) \<40ml/min 30. Others inadequate laboratory values: serum albumin\<30 g/L; troponin \> ULN ; BNP (Brain-Type Natriuretic Peptide) \> ULN. 31. Active alcohol or drug abuse.