Circulating tumor HPV DNA assessments after surgery for human papilloma virus-associated oropharynx carcinoma.

PURPOSE: To understand the utility of circulating tumor human papillomavirus DNA (ctHPVDNA) blood testing for HPV-associated oropharynx squamous cell carcinoma (HPV + OPSCC) after definitive surgery. MATERIALS AND METHODS: Prospective cohort study of HPV(+)OPSCC patients with ctHPVDNA test data to assess its accuracy in detecting biopsy-confirmed disease at various post-treatment time points. Eligible patients had p16(+)/HPV(+) OPSCC and ctHPVDNA testing performed at any time pre-operatively and/or postoperatively. In cases of recurrence, patients were excluded from analysis if ctHPVDNA testing was not performed within 6 months of biopsy. RESULTS: 196 all-treatment-type patients had at least one PT ctHPVDNA test. The initial post-treatment (PT) ctHPVDNA sensitivity, specificity, PPV, and NPV were 69.2 % (9/13), 96.7 % (177/183), 60.0 % (9/15), and 97.8 % (177/181). 61 surgery alone (SA) patients underwent 128 PT tests. The initial PT SA ctHPVDNA sensitivity, specificity, PPV, and NPV were 100 % (2/2), 96.0 % (48/50), 50 % (2/4), and 100 % (48/48). 35 of 61 (57.4 %) SA patients had NCCN-based histopathologic indications for adjuvant (chemo)radiation but declined. 3 of 35 (8.57 %) had a positive PT ctHPVDNA test of which 1 of 3 (33 %) had biopsy-proven recurrence. Prospectively, ten patients had a PreT positive ctHPVDNA, underwent SA, refused adjuvant treatment, had an undetectable ctHPVDNA within 2 weeks of SA, and remained free of disease (mean 10.3 months). CONCLUSION: The high specificity and NPV of ctHPVDNA after SA suggest ctHPVDNA may have a role in determining the omission of PT adjuvant (chemo)radiation in select patients.

Prospective quality of life outcomes for human papillomavirus associated oropharynx cancer patients after surgery alone.

PURPOSE: To evaluate changes in patient-reported quality of life (QOL) to inform treatment decisions for human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC). MATERIALS AND METHODS: Patients with American Joint Committee on Cancer (AJCC) 8th edition cT0-T3 and cN0-N3 HPV + OPSCC treated with transoral robotic surgery to the primary site with neck dissection completed questionnaires prior to surgery and at three-months and one-year post-operatively. Questionnaires included four validated instruments: the University of Washington Quality of Life Questionnaire (UW-QOL), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Head and Neck Module (HN35), and the Neck Dissection Impairment Index (NDII). RESULTS: Forty-eight patients filled out pretreatment and three-month questionnaires. 37 patients filled out one-year questionnaires. With the UW-QOL, at three-months, patients reported a statistically significant and clinically meaningful decreased mean score for appearance that resolved at one-year (presurgery: 92.4, 3-month: 81.0, p < 0.001; one year: 86.5). At three months and one-year, significant and clinically meaningful decreased mean taste scores persisted (presurgery: 98.0; three-months: 76.3, one-year: 80.3; all p < 0.001). With the EORTC QLQ-C30 and HN35, at one-year, only mean scores for sense of taste or smell (one-year: 13.1; p < 0.001) did not return to baseline. With the NDII, patients returned to functions comparable to baseline in all domains. CONCLUSION: Post-treatment quality of life is high for HPV+ OPSCC patients treated with surgery alone. Mild taste and possibly smell dysfunction may continue in some patients. With careful selection, surgery alone for HPV + OPSCC offers favorable QOL outcomes. LAY SUMMARY: Patients with HPV+ associated oropharynx cancer treated with surgery alone completed quality of life questionnaires before and after surgery. Quality of life remained high for most patients, with a subset of patients experiencing mild taste dysfunction one-year after surgery.

A prospective evaluation of neck and shoulder function following treatments of early-stage human papillomavirus-associated oropharynx cancer.

OBJECTIVES: To compare post-treatment neck and shoulder function between human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC) treatments. DESIGN: Prospective, repeated-measures study. SETTING: Tertiary care center. PARTICIPANTS: Treatment-naïve patients with American Joint Committee on Cancer eighth edition stage T0-3/N0-2 HPV+OPSCC. MAIN OUTCOME MEASURES: Patients completed the Neck Dissection Impairment Index (NDII) pre-treatment and 3-months and 1-year post-treatment. The NDII assesses 10 neck and shoulder functions scored 0-5 (total score 0-100), with higher scores suggesting better function. RESULTS: A total of 106 patients underwent: surgery alone (SA, n = 46, 43%), surgery with adjuvant radiation ± chemotherapy (S + a[C]XRT, n = 18, 17%), or definitive radiation ± chemotherapy (d[C]XRT, n = 42, 40%). cTN classification and pre-treatment NDII scores did not differ between groups. SA patients reported worsened 3-month post-treatment versus pre-treatment self-care (4.6 vs. 5.0), lifting light (4.6 vs. 5.0) and heavy (4.2 vs. 4.8) objects, overhead reach (4.5 vs. 4.9), activity (4.5 vs. 4.9), socialization (4.7 vs. 4.9), recreation (4.6 vs. 4.9), and overall score (86.8 vs. 95.3) (all p < 0.05). One-year post-treatment scores (n = 34) were no different than pre-treatment in all domains. S + a[C]XRT patients reported worsened 3-month versus pre-treatment stiffness (4.0 vs. 4.8), lifting heavy objects (3.8 vs. 4.9), overhead reach (4.2 vs. 4.9), socialization (4.6 vs. 5.0), recreation (4.4 vs. 4.9) and overall score (82.4 vs. 96.0) (all p < 0.05). One-year post-treatment scores (n = 13) were no different than pre-treatment in all domains. d[C]XRT patients reported worsened 3-month versus pre-treatment difficulty lifting heavy objects (4.3 vs. 4.7) and recreation (4.3 vs. 4.7). One-year posttreatment scores (n = 21) were no different than pre-treatment in all domains. CONCLUSION: HPV + OPSCC patients may experience mild shoulder/neck dysfunction 3 months after treatment that usually resolves by 1 year, independent of treatment modality.

Oncologic outcomes of human papillomavirus-associated oropharynx carcinoma treated with surgery alone: A 12-institution study of 344 patients.

BACKGROUND: The oncologic outcomes of surgery alone for patients with American Joint Committee on Cancer 7th edition (AJCC 7th) pN2a and pN2b human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+OPSCC) are not clear. METHODS: The authors performed a 12-institution retrospective study of 344 consecutive patients with HPV+OPSCC (AJCC 7th pT0-3 N3 M0) treated with surgery alone with 6 months or more of follow-up using univariate and multivariate analyses. RESULTS: The 2-year outcomes for the entire cohort were 91% (182 of 200) disease-free survival (DFS), 100% (200 of 200) disease-specific survival (DSS), and 98% (200 of 204) overall survival (OS). The 18 recurrences within 2 years were 88.9% (16 of 18) local and/or regional recurrences and 11.1% (2 of 18) distant metastases. Recurrences were not significantly associated with smoking, pT stage, or pN stage. The 16 patients with locoregional recurrences within 2 years all underwent successful salvage treatments (median follow-up after salvage: 13.1 months), 43.8% (7 of 16) of whom underwent salvage surgery alone for a 2-year overall salvage radiation need of 4.5% (9 of 200). The 2-year outcomes for the 59 evaluable patients among the 109 AJCC 7th pT0-2 N2a-N2b patients with 1 to 3 pathologic lymph nodes (LNs) were as follows: local recurrence, 3.4% (2 of 59); regional recurrence, 8.4% (5 of 59); distant metastases, 0%; DFS, 88.1% (52 of 59); DSS, 100% (59 of 59); OS, 96.7% (59 of 61); and salvage radiation, 5.1% (3 of 59). CONCLUSIONS: With careful selection, surgery alone for AJCC 7th pT0-T2N0-N2b HPV+OPSCC with zero to 3 pathologic LNs without perineural invasion, extranodal extension, or positive margins results in high DFS, DSS, OS, and salvage treatment success. Because of the short-term follow-up, these data support further investigation of treatment de-escalation in this population.

Assessment of Variability in Free Flap Color Match to Facial Skin by Donor Site and Race.

OBJECTIVES: To use portable colorimetry to quantify color differences between facial skin and potential three head and neck microvascular free tissue transfer (MFTT) donor sites-radial forearm (RF), anterolateral thigh (ALT), and fibula (FF)-and compare these differences by pigmentation of the donor site skin and self-identified race. METHODS: In this cross-sectional cohort study, healthy volunteers consented to handheld colorimeter measurements at the three potential MFTT donor sites (RF, ALT, FF) to quantify color match to the facial skin using the CIE color space (DeltaE). The comparison of ipsilateral to contralateral cheek served as control for measurements. Cross-sectional measurements in healthy volunteers were then compared to measurements obtained in postoperative head and neck MFTT patients. RESULTS: DeltaE measurements were obtained for 128 healthy controls and 24 postoperative patients (N = 152). With increasing lightness (decreased pigmentation) of the skin at the donor site, the color match significantly worsened (higher DeltaE) across all potential MFTT donor sites (all p < 0.05). DeltaE from healthy controls closely approximated postoperative color match measurements in patients who underwent cervicofacial MFTT (DeltaE RF: 5.3 vs. 6.0, p = 0.432; DeltaE ALT: 6.2 vs. 6.4, p = 0.822; DeltaE FF: 6.0 vs. 6.4, p = 0.806). CONCLUSION: Patients with decreased skin pigmentation who are undergoing head and neck MFTT may experience worse color discrepancy between cervicofacial skin and the transferred skin paddle than those with more pigmented skin. Portable colorimetry may identify patients who could benefit from interventions such as dermis-resected free tissue reconstruction with skin grafting to improve postoperative appearance. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Increasing Pedicle Reach with Musculocutaneous Perforator Dissection in Anterolateral Thigh Free Flaps.

OBJECTIVE: To measure the increase in effective pedicle reach with microdissection of musculocutaneous perforators during anterolateral thigh (ALT) free tissue harvest. METHODS: A review of our institution's free flap database was performed to identify ALT free tissue transfers. The distance from pedicle vessel origin to its perforator's insertion at the fascia lata (effective pedicle length [EPL]) was measured prior to and following intramuscular dissection of musculocutaneous perforators. Pertinent clinicopathologic variables were abstracted from the electronic medical record. RESULTS: A total of 314 ALT free flaps were performed between February 2017 and August 2022. Of these, 85 had documentation of EPL before and after musculocutaneous perforator dissection. ALT reconstruction was primarily performed for reconstruction of oncologic ablative defects (66, 78%). The mean EPL prior to perforator microdissection was 8.8 cm (standard deviation, SD 2.8 cm; range 3-15 cm). Following perforator dissection, mean EPL significantly increased to 14.0 cm (SD 3.0 cm; range 7-22 cm) with a mean net gain of 5.2 cm in distance (95% confidence interval 4.8-5.6 cm; p < 0.001). Nine patients (11%) required operating room take-back for anastomosis revision (3, 3.5%), recipient site hematoma evacuation (4, 4.7%), and wound dehiscence (2, 2.3%); one complete flap loss due to venous thrombosis was observed. CONCLUSION: Dissection of musculocutaneous perforators during ALT free flap harvest can increase effective pedicle reach by 5.2 cm or nearly 60%. This harvest technique can facilitate the performance of tension-free anastomoses when substantial vascular pedicle length or vascular pedicle tunneling is required. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:666-670, 2024.

Treatment Modality Impact on Patient-Reported Quality of Life in Human Papilloma Virus-Associated Oropharyngeal Carcinoma.

OBJECTIVE: To prospectively compare the impact of treatment modality on patient-reported quality of life (QOL) in human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC). STUDY DESIGN: Prospective cohort study. SETTING: Academic medical center. METHODS: One hundred one patients with American Joint Committee on Cancer (AJCC) 8th edition T1-3 N0-2 HPV + OPSCC completed the European Organization for Research and Treatment of Cancer Quality of Life Core questionnaire and Head and Neck Module pretreatment and 3-month and 1-year posttreatment. Mean score changes were compared to published minimal clinically important differences. RESULTS: Patients underwent surgery alone (SA: N = 42, 42%), surgery with adjuvant radiation (S-RT: N = 10, 10%), surgery with adjuvant chemoradiation (S-CRT: N = 8, 8%), definitive radiation (RT: N = 11, 11%), or definitive chemoradiation (CRT: N = 30, 30%). SA, S-[C]RT, and [C]RT patients all reported clinically significant difficulty with sense of taste/smell persisting at 1 year. S-[C]RT and [C]RT patients reported statistically and clinically significant worse salivary dysfunction and problems with social eating at 1 year than SA. S-[C]RT patients reported statistically and clinically significant worse fatigue and head and neck pain compared to [C]RT and SA patients at 3 months, but normalized at 1 year. S-CRT compared to S-RT had statistically and clinically worse physical and role functioning and swallowing difficulties at 3 months but this difference was resolved by 1-year posttreatment. CONCLUSION: HPV + OPSCC patients after SA report the lowest posttreatment QOL impact, whereas after S-CRT report the highest symptom burden. Careful selection for definitive surgery is important given the possibility of adjuvant CRT. Patients can experience persistent sense taste and smell difficulties at 1 year with all treatment modalities. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1687-1695, 2024.

Oncologic Safety of Close Margins in Patients With Low- to Intermediate-Grade Major Salivary Gland Carcinoma.

Importance: Postoperative radiation therapy for close surgical margins in low- to intermediate-grade salivary carcinomas lacks multi-institutional supportive evidence. Objective: To evaluate the oncologic outcomes for low- and intermediate-grade salivary carcinomas with close and positive margins. Design, Setting, and Participants: The American Head and Neck Society Salivary Gland Section conducted a retrospective cohort study from 2010 to 2019 at 41 centers. Margins were classified as R0 (negative), R1 (microscopically positive), or R2 (macroscopically positive). R0 margins were subclassified into clear (>1 mm) or close (≤1 mm). Data analysis was performed from June to October 2023. Main Outcomes and Measures: Main outcomes were risk factors for local recurrence. Results: A total of 865 patients (median [IQR] age at surgery, 56 [43-66] years; 553 female individuals [64%] and 312 male individuals [36%]) were included. Of these, 801 (93%) had parotid carcinoma and 64 (7%) had submandibular gland carcinoma, and 748 (86%) had low-grade tumors and 117 (14%) had intermediate-grade tumors, with the following surgical margins: R0 in 673 (78%), R1 in 168 (19%), and R2 in 24 (3%). Close margins were found in 395 of 499 patients with R0 margins (79%), for whom margin distances were measured. A total of 305 patients (35%) underwent postoperative radiation therapy. Of all 865 patients, 35 (4%) had local recurrence with a median (IQR) follow-up of 35.3 (13.9-59.1) months. In patients with close margins as the sole risk factor for recurrence, the local recurrence rates were similar between those who underwent postoperative radiation therapy (0 of 46) or observation (4 of 165 [2%]). Patients with clear margins (n = 104) had no recurrences. The local recurrence rate in patients with R1 or R2 margins was better in those irradiated (2 of 128 [2%]) compared to observed (13 of 64 [20%]) (hazard ratio [HR], 0.05; 95% CI, 0.01-0.24). Multivariable analysis for local recurrence found the following independent factors: age at diagnosis (HR for a 10-year increase in age, 1.33; 95% CI, 1.06-1.67), R1 vs R0 (HR, 5.21; 95% CI, 2.58-10.54), lymphovascular invasion (HR, 4.47; 95% CI, 1.43-13.99), and postoperative radiation therapy (HR, 0.10; 95% CI, 0.04-0.29). The 3-year local recurrence-free survivals for the study population were 96% vs 97% in the close margin group. Conclusions and Relevance: In this cohort study of patients with low- and intermediate-grade major salivary gland carcinoma, postoperative radiation therapy for positive margins was associated with decreased risk of local recurrence. In isolation from other risk factors for local recurrence, select patients with close surgical margins (≤1 mm) may safely be considered for observation.

Symptom Outcomes After Sialendoscopy-Assisted Salivary Duct Surgery: A Prospective 6-Year Study.

OBJECTIVE: The objective is to evaluate the long-term impact of sialendoscopic-assisted salivary duct surgery (SASDS) on sialadenitis symptoms using the Chronic Obstructive Sialadenitis Symptoms (COSS) questionnaire. METHODS: The COSS questionnaire, which scores symptoms on a 0-100 scale, was administered prospectively to adult patients pre-operatively, 1-year, and 6-years post-operatively. We examined COSS scores and categories representing complete (<10), partial (10-25), and no (>25) resolution of symptoms with attention to factors significantly associated with incomplete resolution (≥10). RESULTS: Approximately 6-years after SASDS, 111 patients reported scores for 128 symptomatic glands (72 with sialolithiasis, 56 without sialolithiasis). For glands with sialolithiasis, the median COSS score pre-SASDS was 27.5 (interquartile range [IQR]: 13.5-43), which was significantly reduced to 1.0 (IQR: 0-5.5) at 1-year and 1.5 (IQR 0-5) at 6-years postoperatively. Glands without sialolithiasis had a median COSS score of 40.5 (IQR: 23-52.5) preoperatively, that significantly reduced to 13.5 (IQR 5-21) at 1-year and 14 (IQR 6.5-25.5) at 6-years post-operatively. There was no significant difference in scores from 1- to 6-years. Intraoperative presence of sialolith, absence of stenosis, stenosis in the distal duct, and submandibular gland involvement were significant predictors of complete resolution of symptoms at 6-years. CONCLUSION: Approximately 6-years after SASDS for sialadenitis, the majority of patients have durable symptom improvement. The sialolithiasis group had higher rates of complete resolution compared to the non-sialolithiasis group. Presence of ductal stenosis on sialendoscopy, non-distal stenoses, and parotid gland involvement were risk factors for persistent long-term sialadenitis symptoms. Laryngoscope, 133:792-800, 2023.

Anterolateral Thigh Free Flap Versus Thigh Split Thickness Skin Graft: Comparison of Morbidity in the First 30 Days.

Background: An anterior thigh split thickness skin graft (AT-STSG) is frequently needed to close the radial forearm free flap (RFFF) donor site, conferring morbidity to two extremities. The anterolateral thigh (ALT) free flap is virtually always closed primarily. Objective: To compare donor site pain, sensation, motor function, and cosmesis associated with the AT-STSG and the ALT. Methods: Patients undergoing an ALT or an RFFF with AT-STSG were enrolled in a prospective observational cohort study. Pain, tingling, numbness, lower extremity function, and subjective donor site cosmetic satisfaction were measured at 1 week and 1 month postoperation using validated instruments. Results: Forty-eight patients were included, with a mean age of 64.2 years (female 31.2%). There were no differences in age or medical comorbidities between the two groups. The average donor defect was 50 and 180 cm2 for the AT-STSG and ALT cohorts, respectively. At 1 week and 1 month postoperatively, we did not detect a difference in donor site pain, pruritus, numbness or tingling, lower extremity function, or subjective cosmetic satisfaction between the two cohorts. Conclusion: ALT primary donor site morbidity, including pain, sensory function, motor function, and cosmesis, is equivalent to RFFF secondary donor site morbidity at 1 week and 1 month postoperatively.

Restarting Therapeutic Antibiotics Following Postoperative Prophylaxis in Head and Neck Microvascular Free Tissue Transfer.

OBJECTIVE: To determine factors associated with restarting therapeutic antibiotics within 30 days of head and neck microvascular free tissue transfer (HN-MFTT). STUDY DESIGN: Retrospective study of consecutive HN-MFTTs performed from January 2015 to July 2020. SETTING: Tertiary academic medical center. METHODS: Thirty-day postoperative antibiotic use and post-HN-MFTT surgical and medical complications were assessed. Univariable analyses and multivariable logistic regression were used to evaluate risk factors associated with restarting antibiotics. RESULTS: overall 482 patients with 501 HN-MFTTs were stratified by duration of prophylaxis: ≤24 hours (n = 136, 27.1%), 25-72 hours (n = 54, 10.8%), and >72 hours (n = 311, 62.1%). Antibiotics were restarted in 199 patients (209 procedures, 42%). The most common indications for antibiotic reinitiation were flap recipient site infection (n = 59, 28%); hospital-acquired pneumonia (n = 44, 21%); and wound dehiscence, fluctuance, or change in quality of drain output (n = 44, 21%). Shorter antibiotic prophylaxis (≤24 hours) (odds ratio [OR], 1.95; 95% CI, 1.2-3.0; P = .003), osteocutaneous flaps (OR, 2.15; 95% CI, 1.3-3.4; P = .001), and prior immunotherapy/chemotherapy (OR, 2.29; 95% CI, 1.2-4.3; P = .01) were associated with reinitiation of antibiotics for surgical infections. Restarting antimicrobials for nosocomial infections was associated with aerodigestive defects (OR, 2.45; 95% CI, 1.1-5.2; P = .019), cardiovascular disease (OR, 3.00; 95% CI, 1.5-5.9; P = .001), and medical comorbidities approximated by American Society of Anesthesiologists class 3 or 4 (OR, 2.83; 95% CI, 1.5-5.4; P = .002). CONCLUSION: Aerodigestive reconstruction, 24-hour postoperative antimicrobial prophylaxis, American Society of Anesthesiologists class 3 and 4, prior chemotherapy/immunotherapy, cardiovascular disease, and osteocutaneous flaps are associated with reinitiation of antibiotics within 30 days of HN-MFTT.

Parapharyngeal tuberculoid mass: A rare complication of Bacillus Calmette-Guérin therapy for urothelial carcinoma in situ.

Local and systemic complications of Bacillus Calmette-Guérin therapy are important to recognize as they require prolonged antimicrobial therapy; molecular genomic testing may be key to diagnosis when culture data are inconclusive.