Alpelisib in Treating Participants With Transorally Resectable HPV-Associated Stage I-IVA Oropharyngeal Cancer

PRIMARY OBJECTIVES: I. To assess the preliminary efficacy of neoadjuvant Alpelisib (BYL719) in patients with transorally-resectable, HPV+ head and neck squamous cell carcinoma (HNSCC), as measured by quantitative change in tumor size (change in T) following 14-21 days of treatment. II. To evaluate the relationship between genomic PIK3CA activation to change in T. SECONDARY OBJECTIVES: I. To describe the tolerability of brief neoadjuvant exposure to BYL719. II. To assess the effect of BYL719 on the tumoral Ki-67 proliferation index. III. To evaluate viral and molecular mediators of response and resistance to BYL719, including viral messenger ribonucleic acid (mRNA), E6 and E7 oncoproteins, and phosphorylated (p)HER3. OUTLINE: Participants receive Alpelisib orally (PO) once daily (QD) for 14-21 days in the absence of disease progression of unacceptable toxicity and then undergo surgery. Participants may receive Alpelisib for up to 28 days if surgery is delayed. After completion of study treatment, participants are followed up for up to 12 weeks.