Pre-operative Atezolizumab in Patients With Resectable, Human Papillomavirus Related Oropharyngeal Carcinoma

Inclusion Criteria:

* The subject is \>= 18 years old on the day of consent
* Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (eg, male or female condom) during the course of the study and for 5 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 5 months after the last dose of study drug(s).
* Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons.
* A male participant must agree to use a contraception as detailed in this protocol during the treatment period and for at least during the active treatment plus an additional 90 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose\] after the last dose of study treatment and refrain from donating sperm during this period.
* The subject has a histologic or cytologic diagnosis of squamous cell carcinoma of the oropharynx, Stage 1 (T1/2 N1) Squamous Cell Carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a clinical laboratory improvement act (CLIA) approved laboratory.
* Patients must not have evidence of extensive or "matted/ fixed" pathologic adenopathy on preoperative imaging.
* The subject has had an assessment of all known disease sites eg, by computerized tomography (CT) scan, magnetic resonance imaging (MRI), bone scan or positron emission tomography (PET)/CT scan as appropriate, within 28 days before the first dose of therapy
* The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document
* Criteria related to comparator drug or background therapy, if applicable: No prior radiation above the clavicles. Patients with a history of a curatively treated malignancy must be disease-free for at least two years prior to entry on study except for carcinoma in situ of cervix, melanoma in-situ (if fully resected), and/or non-melanomatous skin cancer
* Age \>= 18 years at time of signing Informed Consent Form
* Ability to comply with the study protocol
* Histologically or cytologically confirmed p16+ HPV-driven OPSCC
* Availability of a representative tumor specimen for exploratory biomarker research
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (1500/GL) without granulocyte colony-stimulating factor support obtained within 14 days prior to initiation of study treatment
* Lymphocyte count \>= 0.5 x 10\^9/L (500/GL) obtained within 14 days prior to initiation of study treatment
* Platelet count \>= 100 x 10\^9/L (100,000/GL) without transfusion obtained within 14 days prior to initiation of study treatment
* Hemoglobin \>= 90 g/L (9 g/dL) obtained within 14 days prior to initiation of study treatment.

  * Patients may be transfused to meet this criterion
* Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) =\< 2.5 x upper limit of normal (ULN), obtained within 14 days prior to initiation of study treatment with the following exceptions:

  * Patients with documented liver metastases: AST and ALT =\< 5 x ULN
  * Patients with documented liver or bone metastases: ALP =\< 5 x ULN
* Serum bilirubin =\< 1.5 x ULN obtained within 14 days prior to initiation of study treatment with the following exception:

  * Patients with known Gilbert disease: serum bilirubin =\< 3 x ULN
* Serum creatinine =\< 1.5 x ULN obtained within 14 days prior to initiation of study treatment
* Serum albumin \>= 25 g/L (2.5 g/dL) obtained within 14 days prior to initiation of study treatment
* For patients not receiving therapeutic anticoagulation: international normalization ratio (INR) or activated partial thromboplastin time (aPTT) =\< 1.5 x ULN obtained within 14 days prior to initiation of study treatment
* For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
* Negative human immunodeficiency virus (HIV) test at screening, with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count \>= 200/uL, and have an undetectable viral load
* Negative hepatitis B surface antigen (HBsAg) test at screening
* Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening. The HCV RNA test must be performed for patients who have a positive HCV antibody test

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from study entry:

* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
* 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, 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:

  * Rash must cover \< 10% of body surface area
  * Disease is well controlled at baseline and requires only low-potency topical corticosteroids
  * There has been 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
* History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* Active tuberculosis
* History of leptomeningeal disease
* Uncontrolled tumor-related pain
* Patients requiring pain medication must be on a stable regimen at study entry
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) Patients with indwelling catheters (e.g., PleurX) are allowed.
* Uncontrolled or symptomatic hypercalcemia (ionized calcium \>1.5 mmol/L, calcium \>12mg/dL or corrected serum calcium \>ULN)
* 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, or any active infection that could impact patient safety.
* 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.
* Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
* 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 study
* History of malignancy must have been treated with curative intent and must be disease free for 1 year prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%), such as adequately treated carcinoma in situ of the cervix or non-melanoma skin carcinoma
* Prior allogeneic stem cell or solid organ transplantation
* Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
* Current treatment with anti-viral therapy for HBV
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
* Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
* Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:

  * Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.
  * Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
* Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment
* Glomerular filtration rate \< 29 mL/min/1.73 m\^2 as calculated through use of the Chronic Kidney Disease Epidemiology Collaboration equation
* An ANC \< 1.5 x 10\^9/L (1500/GL) with one exception:

  * Patients with benign ethnic neutropenia (BEN): ANC \< 1.3 x 10\^9/L (1300GL) BEN (also known as constitutional neutropenia) is an inherited cause of mild or moderate neutropenia that is not associated with any increased risk for infections or other clinical manifestations. BEN is referred to as ethnic neutropenia because of its increased prevalence in people of African descent and other specific ethnic groups