Phosphorylation of Merkel cell polyomavirus large tumor antigen at serine 816 by ATM kinase induces apoptosis in host cells.

Merkel cell carcinoma is a highly aggressive form of skin cancer. Merkel cell polyomavirus (MCV) infection and DNA integration into the host genome correlate with 80% of all Merkel cell carcinoma cases. Integration of the MCV genome frequently results in mutations in the large tumor antigen (LT), leading to expression of a truncated LT that retains pRB binding but with a deletion of the C-terminal domain. Studies from our laboratory and others have shown that the MCV LT C-terminal helicase domain contains growth-inhibiting properties. Additionally, we have shown that host DNA damage response factors are recruited to viral replication centers. In this study, we identified a novel MCV LT phosphorylation site at Ser-816 in the C-terminal domain. We demonstrate that activation of the ATM pathway stimulated MCV LT phosphorylation at Ser-816, whereas inhibition of ATM kinase activity prevented LT phosphorylation at this site. In vitro phosphorylation experiments confirmed that ATM kinase is responsible for phosphorylating MCV LT at Ser-816. Finally, we show that ATM kinase-mediated MCV LT Ser-816 phosphorylation may contribute to the anti-tumorigenic properties of the MCV LT C-terminal domain.

Association of a peptoid ligand with the apical loop of pri-miR-21 inhibits cleavage by Drosha.

We have found a small molecule that specifically inhibits cleavage of a precursor to the oncogenic miRNA, miR-21, by the microprocessor complex of Drosha and DGCR8. We identified novel ligands for the apical loop of this precursor from a screen of 14,024 N-substituted oligoglycines (peptoids) in a microarray format. Eight distinct compounds with specific affinity were obtained, three having affinities for the targeted loop in the low micromolar range and greater than 15-fold discrimination against a closely related hairpin. One of these compounds completely inhibits microprocessor cleavage of a miR-21 primary transcript at concentrations at which cleavage of another miRNA primary transcript, pri-miR-16, is little affected. The apical loop of pri-miR-21, placed in the context of pri-miR-16, is sufficient for inhibition of microprocessor cleavage by the peptoid. This compound also inhibits cleavage of pri-miR-21 containing the pri-miR-16 apical loop, suggesting an additional site of association within pri-miR-21. The reported peptoid is the first example of a small molecule that inhibits microprocessor cleavage by binding to the apical loop of a pri-miRNA.

Reconstruction of composite oral cavity defects with temporalis flaps after prior treatment.

BACKGROUND: Reconstruction of composite oral cavity defects in the setting of prior surgery and radiotherapy presents a significant challenge. Although free tissue transfer has shown success in such situations, it is not without considerable risk. Regional pedicled flaps may provide a more suitable alternative. In certain patients, however, severe soft tissue fibrosis makes more conventional regional flaps impractical or impossible. In these situations, temporalis flaps (temporalis muscle and temporoparietal fascia flaps) are versatile options for coverage of complex defects. OBJECTIVE: To report our experience using pedicled temporalis flaps for reconstruction of composite oral cavity defects in patients with significant co-morbidities and prior treatment. METHODS: Three patients were identified and their medical records were reviewed. Their clinical courses and functional outcomes are described. We include a discussion of the operative technique and relevant literature. RESULTS: All patients had previously undergone extensive treatment. One patient needed reconstruction after resection of a third head and neck malignancy and two patients presented for treatment of osteoradionecrosis. A temporalis muscle flap was used to reconstruct composite oral cavity defects in two patients and a combined temporalis muscle and temporoparietal fascia flap was used for independent defects in one patient. All flaps survived. Functional status and pain improved or stabilized in all patients. There were no major or minor complications. CONCLUSION: In previously treated fields, where more conventional flaps are impractical, temporalis flaps are a suitable alternative to achieve a stable healing wound and prevent worsening of functional status.

Atlantoaxial subluxation and nasopharyngeal necrosis complicating suspected granulomatosis with polyangiitis.

Granulomatosis polyangiitis (GPA, formerly Wegener granulomatosis) is a vasculitis that typically involves the upper respiratory tract, lungs, and kidneys. The 2 established methods to confirm a suspicion of GPA are the antineutrophil cytoplasmic antibody (ANCA) test and biopsy. However, ANCA-negative cases have been known to occur, and it can be difficult to find biopsy evidence of granulomatous disease.We report a case of suspected granulomatosis with polyangiitis limited to the nasopharynx. With a negative ANCA and no histological evidence, our diagnosis was founded on the exclusion of other diagnoses and the response to cyclophosphamide therapy. This case is unique because the patient's lesion resulted in atlantoaxial instability, which required a posterior spinal fusion at C1-C2. This is the first reported case of suspected GPA producing damage to the cervical spine and threatening the spinal cord.

Merkel cell polyomavirus large T antigen disrupts host genomic integrity and inhibits cellular proliferation.

Clonal integration of Merkel cell polyomavirus (MCV) DNA into the host genome has been observed in at least 80% of Merkel cell carcinoma (MCC). The integrated viral genome typically carries mutations that truncate the C-terminal DNA binding and helicase domains of the MCV large T antigen (LT), suggesting a selective pressure to remove this MCV LT region during tumor development. In this study, we show that MCV infection leads to the activation of host DNA damage responses (DDR). This activity was mapped to the C-terminal helicase-containing region of the MCV LT. The MCV LT-activated DNA damage kinases, in turn, led to enhanced p53 phosphorylation, upregulation of p53 downstream target genes, and cell cycle arrest. Compared to the N-terminal MCV LT fragment that is usually preserved in mutants isolated from MCC tumors, full-length MCV LT shows a decreased potential to support cellular proliferation, focus formation, and anchorage-independent cell growth. These apparently antitumorigenic effects can be reversed by a dominant-negative p53 inhibitor. Our results demonstrate that MCV LT-induced DDR activates p53 pathway, leading to the inhibition of cellular proliferation. This study reveals a key difference between MCV LT and simian vacuolating virus 40 LT, which activates a DDR but inhibits p53 function. This study also explains, in part, why truncation mutations that remove the MCV LT C-terminal region are necessary for the oncogenic progression of MCV-associated cancers.

Clinical outcomes following intraoperative pedicle disruption in fibula free flaps.

OBJECTIVES: Iatrogenic injury of the fibula free flap pedicle is rare. Postoperative flap survival and reconstructive outcomes following intraoperative pedicle severance are unknown. This study assesses free flap outcomes following accidental severance of the peroneal vessels. METHODS: Multi-institutional retrospective chart review from 2000 to 2020. RESULTS: Of 2975 harvested fibula free flaps, 26 had a history of pedicle severance during surgical reconstruction. Reasons for intraoperative pedicle severance included transection during muscular dissection 10/26 (39%), accidental severance with the bone saw 12/26 (46%), and other 4/26 (15.6%). The surgeon responsible for pedicle severance included residents 5/26 (19%), fellows 10/26 (39%), attendings 10/26 (39%), and unknown 1/26 (3.9%). The pedicle artery and vein were severed 10/26 (39%), artery 8/26 (31%), and vein 8/26 (31%). Truncated pedicle vessels were used 3/26 (11.7%), intraoperative anastomoses were performed 23/26 (89%). Postoperative revision in the OR within 7 days of surgery was required 6/26 (23%); 4 flaps were salvaged and 2 flaps failed, both arterial thrombosis. Flap failure was attributed to vascular thrombosis. Long-term flap survival and successful reconstructions were reported 24/26 (92%). CONCLUSION: Accidental severance of fibula free flap pedicle vessels can be corrected with intraoperative repair, without affecting long-term flap survival or reconstructive outcomes. Protecting the flap vessels while using the bone saw and during intramuscular dissection prevents accidental severance.

Perturbation of BRD4 protein function by BRD4-NUT protein abrogates cellular differentiation in NUT midline carcinoma.

NUT midline carcinoma (NMC) belongs to a class of highly lethal and poorly differentiated epithelial cancers arising mainly in human midline organs. NMC is caused by the chromosome translocation-mediated fusion of the NUT (nuclear protein in testis) gene on chromosome 15 to a few other genes, most frequently the BRD4 gene on chromosome 19. The mechanism by which the BRD4-NUT fusion product blocks NMC cellular differentiation and contributes to oncogenesis remains elusive. In this study, we show that BRD4-NUT and BRD4 colocalize in discrete nuclear foci that are hyperacetylated but transcriptionally inactive. BRD4-NUT recruits histone acetyltransferases to induce histone hyperacetylation in these chromatin foci, which provide docking sites for accumulation of additional BRD4 and associated P-TEFB (positive transcription elongation factor b) complexes in the transcriptionally inactive BRD4-NUT foci. These molecular events lead to repression of a BRD4·P-TEFB downstream target gene c-fos, a component of activator protein 1 (AP-1), that directly regulates epithelial differentiation. Knockdown of BRD4-NUT in NMC cells disperses the transcriptionally inactive chromatin foci and releases the transcriptional activators to stimulate c-fos expression, leading to restoration of cellular differentiation. Our study provides a novel mechanism by which the BRD4-NUT oncogene perturbs BRD4 functions to block cellular differentiation and to contribute to the oncogenic progression in the highly aggressive NMC.

Instructional Models for Course-Based Research Experience (CRE) Teaching.

The course-based research experience (CRE) with its documented educational benefits is increasingly being implemented in science, technology, engineering, and mathematics education. This article reports on a study that was done over a period of 3 years to explicate the instructional processes involved in teaching an undergraduate CRE. One hundred and two instructors from the established and large multi-institutional SEA-PHAGES program were surveyed for their understanding of the aims and practices of CRE teaching. This was followed by large-scale feedback sessions with the cohort of instructors at the annual SEA Faculty Meeting and subsequently with a small focus group of expert CRE instructors. Using a qualitative content analysis approach, the survey data were analyzed for the aims of inquiry instruction and pedagogical practices used to achieve these goals. The results characterize CRE inquiry teaching as involving three instructional models: 1) being a scientist and generating data; 2) teaching procedural knowledge; and 3) fostering project ownership. Each of these models is explicated and visualized in terms of the specific pedagogical practices and their relationships. The models present a complex picture of the ways in which CRE instruction is conducted on a daily basis and can inform instructors and institutions new to CRE teaching.

Transoral robotic surgery of the skull base: a cadaver and feasibility study.

OBJECTIVE: The goal of this study was to determine the potential role as well as the current limitations of the da Vinci Surgical System robot in transoral surgery of the skull base. METHODS: The da Vinci robot was used to perform dissections of the skull base on 7 cadaver heads with their neck and clavicles intact. Neurosurgeons and otolaryngologists familiar with all facets of the open microscopic, minimally invasive, endoscopic and transoral robotic surgical procedure proceeded with the approach to and dissection of the human skull base. RESULTS: The da Vinci robot provided superb illumination and 3-dimensional depth perception. The 30-degree endoscope improved cephalad visualization, and the 'intuitive' nature of the da Vinci surgical robot arms provided an advantage by their ability to suture the dura at the level of the clivus. An entirely transoral route provides access to the middle and lower clivus as well as the infratemporal fossa, but access to the sellar region and anterior cranial fossa is limited via a purely transoral route. Tremor-free dural closure was successfully performed. CONCLUSION: Our findings suggest that transoral robotic surgery utilizing the da Vinci robot system holds great potential for skull base surgical resection of extradural and intradural tumors of the middle and lower clivus and infratemporal fossa. A collaborative approach with neurosurgeon and otolaryngologist alternating at the master console and bedside is a successful strategy. Further instrument development is necessary, and continued investigation is warranted.

Hexakis(acetonitrile-κN)ruthenium(II) bis-(hexa-bromo-carbadodeca-borate) aceto-nitrile solvate.

The title compound, [Ru(NCCH(3))(6)](CH(6)B(11)Br(6))(2)·CH(3)CN, consists of the 'naked' ruthenium(II) cation surrounded by six acetonitrile mol-ecules, each coordinated via the nitro-gen atoms in a linear or nearly-linear fashion in a typical octa-hedral over-all arrangement. The cation is balanced by the two hexa-bromo-carborane cage anionic fragments [CB(11)H(6)Br(6)]. Weak C-H⋯Br and B-H⋯Br inter-actions link neighboring anions.

A different approach to orbital blow out fractures: microscope-assisted reconstruction of the orbital floor.

To describe a different surgical approach to treat pediatric orbital floor fractures. We report the case of a 14-year-old boy who underwent a microscope-assisted repair of his orbital floor fracture 6 weeks after his injury. The microscope provided excellent visualization of the entire orbital floor defect and facilitated placement of a polyethylene implant. The repair was achieved without complications, and follow-up examinations demonstrated improvement in patient's enophthalmos and diplopia. We noted significant advantages with a microscope-assisted repair over an endoscopic technique for this condition. The operating microscope allows for two-handed surgery, does not require withdraw of the endoscope for cleaning, and provides depth of field. A larger patient population and longer follow-up are needed to better assess the clinical efficacy of this technique.

Multiple Myeloma Presenting as Massive Amyloid Deposition in a Parathyroid Gland Associated with Amyloid Goiter: A Medullary Thyroid Carcinoma Mimic on Intra-operative Frozen Section.

Clinical examples of amyloid deposition in parathyroid glands are exceedingly rare and usually present as an incidental finding in a patient with amyloid goiter. Here, we present the first histologically documented case of parathyroid amyloid deposition that presented as a mass. The patient did not have hyperparathyroidism. The parathyroid gland was submitted for intra-operative frozen section and concern for medullary thyroid carcinoma was raised. An important histologic clue arguing against medullary thyroid carcinoma was the evenly dispersed nature of the amyloid. Histologic perinuclear clearing and parathyroid hormone immunohistochemistry confirmed parathyroid origin on permanent sections. The patient was also found to have associated amyloid goiter. Mass spectrometry of the amyloid showed it to be composed of kappa light chains. On further work-up, the patient was diagnosed with multiple myeloma. Awareness of parathyroid amyloid deposition is important as it is a histologic mimic of medullary thyroid carcinoma, especially on frozen section. Amyloid typing with evaluation for multiple myeloma in any patient with kappa or lambda light chain restriction is also important.

Eliminating the limitations of manual crimping in stapes surgery: mid-term results of 90 patients in the Nitinol stapes piston multicenter trial.

OBJECTIVE: To present our mid-term results of our multicenter study using the Nitinol self-crimping stapes piston, focusing on the interindividual variations of postoperative air-bone gap closures (ABGC), postoperative hearing results, and postoperative recurrences of conductive hearing loss and to compare these findings with our pilot group of patients. STUDY DESIGN: Prospective, multicenter cohort study involving three academic tertiary care referral centers from Australia, Switzerland, and the United States. METHODS: Ninety patients with otosclerosis undergoing laser-stapedotomy with the Nitinol stapes piston were matched to reference patients from our titanium piston database. The effects of the self-crimping Nitinol piston on the postoperative ABGC, the postoperative interindividual air-bone gap (ABG) variations, and the postoperative hearing results were investigated 3, 6, 12, 18, and 24 months postoperatively. These data were statistically compared with the results of the control patients in our titanium stapes piston database and the results of our previously published pilot study. RESULTS: The mean postoperative ABG and the interindividual variations of the postoperative ABG continue to be significantly smaller in the Nitinol group; the extent of ABGC now is significantly larger in the Nitinol piston group. The postoperative mid-term stability of ABGC was similar in both groups. No adverse reactions occurred during follow-up. CONCLUSION: Our mid-term results continue to show that the self-crimping shape memory alloy Nitinol stapes piston overcomes the limitations of manual malcrimping in stapedotomy, thus simplifying and optimizing the surgical procedure. This so far has allowed reliable, safe, and consistent ABGC in patients with otosclerosis.

Biomarker and Tumor Responses of Oral Cavity Squamous Cell Carcinoma to Trametinib: A Phase II Neoadjuvant Window-of-Opportunity Clinical Trial.

Purpose: Ras/MEK/ERK pathway activation is common in oral cavity squamous cell carcinoma (OCSCC). We performed a neoadjuvant (preoperative) trial to determine the biomarker and tumor response of OCSCC to MEK inhibition with trametinib.Experimental Design: Patients with stage II-IV OCSCC received trametinib (2 mg/day, minimum 7 days) prior to surgery. Primary tumor specimens were obtained before and after trametinib to evaluate immunohistochemical staining for p-ERK1/2 and CD44, the primary endpoint. Secondary endpoints included changes in clinical tumor measurements and metabolic activity [maximum standardized uptake values (SUVmax) by F-18 fluorodeoxyglucose positron emission tomography/CT), and in tumor downstaging. Drug-related adverse events (AE) and surgical/wound complications were evaluated.Results: Of 20 enrolled patients, 17 (85%) completed the study. Three patients withdrew because of either trametinib-related (n = 2: nausea, duodenal perforation) or unrelated (n = 1: constipation) AEs. The most common AE was rash (9/20 patients, 45%). Seventeen patients underwent surgery. No unexpected surgical/wound complications occurred. Evaluable matched pre- and posttrametinib specimens were available in 15 (88%) of these patients. Reduction in p-ERK1/2 and CD44 expression occurred in 5 (33%) and 2 (13%) patients, respectively. Clinical tumor response by modified World Health Organization criteria was observed in 11 of 17 (65%) evaluable patients (median 46% decrease, range 14%-74%). Partial metabolic response (≥25% reduction in SUVmax) was observed in 6 of 13 (46%) evaluable patients (median 25% decrease, range 6%-52%). Clinical-to-pathologic tumor downstaging occurred in 9 of 17 (53%) evaluable patients.Conclusions: Trametinib resulted in significant reduction in Ras/MEK/ERK pathway activation and in clinical and metabolic tumor responses in patients with OCSCC. Clin Cancer Res; 23(9); 2186-94. ©2016 AACR.

Granulomatosis with polyangiitis (Wegener's granulomatosis) causing atlantoaxial instability: a case report.

BACKGROUND CONTEXT: No previous cases of atlantoaxial instability due to granulomatosis with polyangiitis have been reported. PURPOSE: The aim of this study was to report a case of granulomatosis with polyangiitis causing atlantoaxial instability. STUDY DESIGN: This is a case report. PATIENT SAMPLE: A 45-year-old woman participated in this study. OUTCOME MEASURES: The patient's pain and atlantoaxial instability were resolved. METHODS: A 45-year-old Caucasian woman with a large ulcerative lesion in her oropharynx initially presented with chronic sinusitis, pharyngitis, and severe odynophagia. Years after her original symptoms began, she developed neck pain radiating into her upper trapezial region and shoulders. RESULTS: Atlantoaxial fusion was performed on the patient, resolving her neck, upper trapezial, and shoulder pain. She was diagnosed with granulomatosis with polyangiitis (formerly Wegener's granulomatosis) and treated with cyclophosphamide. CONCLUSIONS: Granulomatosis with polyangiitis should be part of the working differential diagnosis for non-traumatic cervical spine injury. The atlantoaxial instability can be managed with stabilization, and the disease process itself can be treated with cyclophosphamide.

Glycan specificity of neuraminidases determined in microarray format.

Neuraminidases hydrolytically remove sialic acids from glycoconjugates. Neuraminidases are produced by both humans and their pathogens, and function in normal physiology and in pathological events. Identification of neuraminidase substrates is needed to reveal their mechanism of action, but high-throughput methods to determine glycan specificity of neuraminidases are limited. Here we use two glycan labeling reactions to monitor neuraminidase activity toward glycan substrates. While both periodate oxidation and aniline-catalyzed oxime ligation (PAL) and galactose oxidase and aniline-catalyzed oxime ligation (GAL) can be used to monitor neuraminidase activity toward glycans in microtiter plates, only GAL accurately measured neuraminidase activity toward glycans displayed on a commercial glass slide microarray. Using GAL, we confirm known linkage specificities of three pneumococcal neuraminidases and obtain new information about underlying glycan specificity.

Locoregional and free flap reconstruction of the lateral skull base.

Lateral temporal bone reconstruction after ablative surgery for malignancy, chronic infection, osteoradionecrosis, or trauma presents a challenge for the reconstructive surgeon. This complexity is due to the 3D nature of the region, potential dural exposure, and the possible need for external surface repair. Successful reconstruction therefore requires achieving separation of the dura, obliteration of volume defect, and external cutaneous repair. There is significant institutional bias on the best method of reconstruction of these defects. In this review, the advantages and disadvantages of reconstructive options will be discussed as well as the potential pitfalls and complications.

Lower Trapezius Flap for Reconstruction of Posterior Scalp and Neck Defects after Complex Occipital-Cervical Surgeries.

Objectives To review the indications, techniques, and outcomes for a series of patients in whom the lower trapezius flaps was used for repair of complex posterior scalp and neck defects after posterior occipital-cervical surgeries. Design Retrospective case series. Setting Tertiary academic hospital. Participants A retrospective review of cases that required complex occipital-cervical repair was performed to identify patients who underwent reconstruction using the lower trapezius flap. Data collected included demographics, clinical presentations, surgical anatomy, operative techniques, and outcomes with review of the pertinent literature. Outcomes Nine patients who underwent reconstruction using the lower trapezius flap were identified. Prior surgical interventions included five complex tumor resections, two patients with multiple instrumented cervical spine surgeries, one patient with a craniotomy for attempted extracranial to intracranial arterial bypass for a basilar aneurysm repair, and a posterior occipital-cervical decompression after trauma. During the median follow-up period of 7 months, all nine single-stage reconstructions resulted in successful healing without major surgical complications. Conclusion Lower trapezius island flaps provide a reliable option for the reconstruction of complex scalp and neck defects that develop after complex occipital-cervical surgeries.

Pre-radiotherapy feeding tube identifies a poor prognostic subset of postoperative p16 positive oropharyngeal carcinoma patients.

BACKGROUND: This study explores variables associated with poor prognosis in postoperative p16 positive oropharyngeal squamous cell carcinoma (OPSCC) patients undergoing adjuvant radiotherapy or chemoradiotherapy. Specifically, analysis was done related to timing of feeding tube insertion relative to radiotherapy. METHODS: From 1997-2009, of 376 consecutive patients with OPSCC, 220 received adjuvant IMRT, and 97 were p16 positive and eligible. Of these, 23 had feeding tube placement before IMRT (B-FT), 32 during/after IMRT (DA-FT), and 42 had no feeding tube (NO-FT). Feeding tubes were not placed prophylactically. These three groups were analyzed for differential tumor, patient, treatment, and feeding tube characteristics, as well as differences in overall survival (OS), disease free survival (DFS), and distant metastasis free survival (DMFS). RESULTS: Pre-RT FT insertion was associated with higher tumor size and depth, T (but not N) and overall stage, comorbidities, presence of chemotherapy, and less use of transoral laser microsurgery/transoral bovie. Additionally, time from surgery to IMRT completion was also statistically longer in the B-FT group. The feeding tube was permanent in 52% of patients in the B-FT group versus 16% in the DA-FT group (p = 0.0075). The 5-year OS for the NO-FT, DA-FT, and B-FT groups was 90%, 86%, and 50%, respectively. The 5-year DFS for the NO-FT, DA-FT, and B-FT groups was 87.6%, 83.6%, and 42.7%, respectively. Multivariate analysis showed that for OS and DFS, feeding tube placement timing and smoking history were statistically significant. CONCLUSION: Due to the poor prognosis of early FT insertion, the presence of FTs at time of radiotherapy consultation can be used as an alternate marker to identify a subset of p16 positive OPSCC patients that have a poor prognosis.

Nab-paclitaxel-based compared to docetaxel-based induction chemotherapy regimens for locally advanced squamous cell carcinoma of the head and neck.

We previously reported that nab-paclitaxel-based induction chemotherapy (IC) and concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent survival in head and neck squamous cell carcinoma (HNSCC). We compare the disease-specific survival (DSS) and overall survival (OS) between patients given nab-paclitaxel, cisplatin, and fluorouracil with cetuximab (APF-C) and historical controls given docetaxel, cisplatin, and fluorouracil with cetuximab (TPF-C). Patients with locally advanced HNSCC were treated with APF-C (n = 30) or TPF-C (n = 38). After 3 cycles of IC, patients were scheduled to receive cisplatin concurrent with definitive radiotherapy. T and N classification and smoking history were similar between the two groups and within p16-positive and p16-negative subsets. The median duration of follow-up for living patients in the APF-C group was 43.5 (range: 30-58) months versus 52 (range: 13-84) months for TPF-C. The 2-year DSS for patients treated with APF-C was 96.7% [95% Confidence Interval (CI): 85.2%, 99.8%] and with TPF-C was 77.6% (CI: 62.6%, 89.7%) (P = 0.0004). Disease progression that resulted in death was more frequent in the TPF-C group (39%) compared with the APF-C group (3%) when adjusted for competing risks of death from other causes (Gray's test, P = 0.0004). In p16 positive OPSCC, the 2-year DSS for APF-C was 100% and for TPF-C was 74.6% (CI: 47.4%, 94.6%) (P = 0.0019) and the 2-year OS for APF-C was 94.1% (CI: 65.0%, 99.2%) and for TPF-C was 74.6% (CI: 39.8%, 91.1%) (P = 0.013). In p16 negative HNSCC, the 2-year DSS for APF-C was 91.7% (CI: 67.6%, 99.6%) and for TPF-C was 82.6% (CI: 64.4%, 94.8%) (P = 0.092). A 2-year DSS and OS were significantly better with a nab-paclitaxel-based IC regimen (APF-C) compared to a docetaxel-based IC regimen (TPF-C) in p16-positive OPSCC.