Sparing Swallowing-Related Structures Reduces Post-Radiotherapy Dysphagia in Oropharyngeal Cancer.

OBJECTIVE: To identify swallowing-related structures (SRSs) predicting post-radiotherapy dysphagia in oropharyngeal carcinoma patients. MATERIAL AND METHODS: Between September 2020 and October 2022, oropharyngeal cancer patients who had completed radiotherapy at least one year before without recurrence or residuals were selected. They underwent flexible endoscopic evaluation of swallowing (FEES) assessments and dysphagia grading. The mean radiation doses delivered to their SRSs were recalculated. The correlation between radiation doses to each SRS and FEES scores was analysed. RESULTS: Twenty-nine participants, aged 51-73 years, were enrolled. Six patients had received two-dimensional radiotherapy, eight had undergone three-dimensional conformal radiotherapy, and fifteen had received intensity-modulated radiation therapy. Radiation doses to the inferior pharyngeal constrictor, cricopharyngeus and glottic larynx significantly predicted dysphagia for both semisolids (p = 0.023, 0.030 and 0.001) and liquid diets (p = 0.021, 0.013 and 0.002). The esophageal inlet significantly predicted swallowing outcomes for only the liquid diet (p = 0.007). CONCLUSIONS: This study supports that SRS-sparing during radiotherapy for oropharyngeal cancers improves swallowing outcomes.

Coinfections with additional oncoviruses in HPV+ individuals: Status, function and potential clinical implications.

Oncovirus infections account for an estimated 12%-20% of human cancers worldwide. High-risk human papillomavirus (HPV) infection is the etiological agent of some malignancies such as cervical, oropharyngeal, anal, penile, vaginal, and vulvar cancers. However, HPV infection is not the only cause of these cancers or may not be sufficient to initiate cancer development. Actually, certain other risk factors including additional oncoviruses coinfections have been reported to increase the risk of patients exposed to HPV for developing different HPV-related cancers. In the current review, we summarize recent findings about coinfections with different oncoviruses in HPV+ patients from both clinical and mechanistic studies. We believe such efforts may lead to an interesting direction for improving our understanding and developing new treatments for virus-induced cancers.

Acute and definitive management of oropharyngeal hemorrhage in patients with squamous cell carcinoma of the oropharynx.

BACKGROUND: Massive oropharyngeal bleeding post-chemoradiotherapy is a life-threatening condition that requires emergent management. METHODS: This retrospective case series included 11 patients with oropharyngeal squamous cell carcinoma who suffered from massive bleeding during or following treatment with definitive chemoradiotherapy. Details of acute and definitive management of oropharyngeal bleeding are reported. RESULTS: Nine of 11 hemorrhagic events occurred a mean (SD) of 88.6 days (53.6) after radiotherapy. Airway intubation and embolization were performed in 10 of 11 patients, followed by surgery in 7 of 11 patients. The most commonly embolized vessels were the external carotid and lingual arteries. At the time of discharge, 3 of 11 patients had a tracheostomy, and 7 of 11 continued to use a gastrostomy tube. Four patients died. CONCLUSIONS: Hemorrhagic complications in oropharyngeal cancer treatment require emergent responses. Developing a workflow for coordination between multidisciplinary teams can maximize probability of survival and decrease morbidity.

Investigating a Causal Relationship Between Diabetes Mellitus and Oropharyngeal Cancer: A Mendelian Randomization Study.

OBJECTIVE: Previous observational studies reported an association of diabetes mellitus (DM) with oropharyngeal cancer (OPC), however, the potential causality of the association between them remains unclear. METHODS: To explore this causal relationship in individuals of European descent, a two-sample Mendelian randomization (MR) study was conducted. A genome-wide association study (GWAS) of DM was used to represent the exposure factor (T1DM: n = 24,840; T2DM: n = 215,654), and GWAS of OPC represented the outcome (n = 3,448). RESULTS: Forty-one single nucleotide polymorphisms (SNPs) related to T1DM and fifty-four SNPs related to T2DM were identified as effective instrumental variables (IVs) in the two-sample MR analyses. In IVW estimates, neither T1DM nor T2DM significantly contributed to an increased risk of OPC [T1DM: OR 1.0322 (95% CI 0.9718, 1.0963), P = 0.3033; T2DM: OR 0.9998 (95% CI 0.9995, 1.0002), P = 0.2858]. Four other regression models produced similar results. MR-Egger regression results [Cochran's Q statistic was 47.1544 (P = 0.1466) in T1DM, and 35.5084 (P = 0.9512) in T2DM] suggested no horizontal pleiotropy between IVs and outcomes. CONCLUSION: Our findings suggest little evidence to support the genetic role of diabetes mellitus in OPC development in the European population.

Genital and extragenital oncological risk in women with vulvar lichen sclerosus: A multi-center Italian study.

Vulvar lichen sclerosus is a chronic inflammatory disease involving vulvar skin. The risk of developing invasive vulvar cancer for women with LS is reported in the literature, but the risk of extra-vulvar tumors has been under-investigated. This multicentric study aims to estimate the risk of developing cancers in a cohort of women with a diagnosis of vulvar lichen sclerosus. METHODS: A cohort of women diagnosed with and treated for vulvar lichen sclerosus in three Italian gynecological and dermatological clinics (Turin, Florence, and Ferrara) was retrospectively reviewed. Patient data were linked to cancer registries of the respective regions. The risk of subsequent cancer was estimated by dividing the number of observed and expected cases by the standardized incidence ratio. RESULTS: Among 3414 women with a diagnosis of vulvar lichen sclerosus corresponding to 38,210 person-years of follow-up (mean 11.2 years) we identified 229 cancers (excluding skin cancers and tumors present at the time of diagnosis). We found an increased risk of vulvar cancer (standardized incidence ratio = 17.4; 95 % CL 13.4-22.7), vaginal cancer (standardized incidence ratio = 2.7; 95 % CL 0.32-9.771), and oropharyngeal cancer (standardized incidence ratio = 2.5; 95 % CL 1.1-5.0), and a reduced risk of other gynecological tumors (cervical, endometrial, ovarian) and breast cancer. CONCLUSIONS: Patients with vulvar lichen sclerosus should undergo annual gynecological check-up with careful evaluation of the vulva and vagina. The increased risk of oropharyngeal cancer also suggests the need to investigate oropharyngeal cavity symptoms and lesions in patients with vulvar lichen sclerosus.

Investigating Predictive Factors of Dysphagia and Treatment Prolongation in Patients with Oral Cavity or Oropharyngeal Cancer Receiving Radiation Therapy Concurrently with Chemotherapy.

Radiation therapy (RT) treatment for head and neck cancer has been associated with dysphagia manifestation leading to worse outcomes and decrease in life quality. In this study, we investigated factors leading to dysphagia and treatment prolongation in patients with primaries arising from oral cavity or oropharynx that were submitted to radiation therapy concurrently with chemotherapy. The records of patients with oral cavity or oropharyngeal cancer that received RT treatment to the primary and bilateral neck lymph nodes concurrently with chemotherapy were retrospectively reviewed. Logistic regression models were used to analyze the potential correlation between explanatory variables and the primary (dysphagia ≥ 2) and secondary (prolongation of total treatment duration ≥ 7 days) outcomes of interest. The Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) were used to evaluate dysphagia. A total of 160 patients were included in the study. Age mean was 63.31 (SD = 8.24). Dysphagia grade ≥ 2 was observed in 76 (47.5%) patients, while 32 (20%) experienced treatment prolongation ≥ 7 days. The logistic regression analysis showed that the volume in the primary site of disease that received dose ≥ 60 Gy (≥118.75 cc, p < 0.001, (OR = 8.43, 95% CI [3.51-20.26]) and mean dose to the pharyngeal constrictor muscles > 40.6 Gy (p < 0.001, OR = 11.58, 95% CI [4.84-27.71]) were significantly associated with dysphagia grade ≥ 2. Treatment prolongation ≥ 7 days was predicted by higher age (p = 0.007, OR = 1.079, 95% CI [1.021-1.140]) and development of grade ≥ 2 dysphagia (p = 0.005, OR = 4.02, 95% CI [1.53-10.53]). In patients with oral cavity or oropharyngeal cancer that receive bilateral neck irradiation concurrently with chemotherapy, constrictors mean dose and the volume in the primary site receiving ≥ 60 Gy should be kept below 40.6 Gy and 118.75 cc, respectively, whenever possible. Elderly patients or those that are considered at high risk for dysphagia manifestation are more likely to experience treatment prolongation ≥ 7 days and they should be closely monitored during treatment course for nutritional support and pain management.

Antimicrobial photodynamic therapy for the treatment of oral mucositis-A comparative study.

OBJECTIVES: The aim was to evaluate the effectiveness of photobiomodulation and antimicrobial photodynamic therapy in the treatment of oral mucositis. BACKGROUND: Oral Mucositis is a frequent complication of oral cavity and oropharynx cancer. Considering the OM aggravation by microorganisms contamination, disinfection provide by antimicrobial photodynamic therapy could be an effective approach. MATERIAL AND METHODS: This comparative study included fourteen patients undergoing radiochemotherapy for oral cavity and oropharynx cancer treatment, who developed oral mucositis. CONTROL GROUP: photobiomodulation. Intervention group: photobiomodulation and antimicrobial photodynamic therapy. The lesion size, duration, pain, and identification of microorganisms were evaluated. RESULTS: The mean reduction in oral mucositis size in the intervention group was 0.70 cm² (±0.35) and 0.30 cm² (±1.10) for the control group. The mean duration of oral mucositis was 18.37 days (±12.12) for the intervention group and 23 days (±14.78) for the control group. The intervention group had a mean reduction of 3.40 points on the pain scale (±2.44), while the control group had 0.17 (±2.28). In the intervention group, the predominant isolated microbiota was featured as mixed culture (n = 4/ 50%), followed of Gram Positive (n = 3/ 37.50%), and Gram Negative (n = 1/ 12.55%). In the control group, mixed culture was also more frequent (n = 4 / 66%), followed by Gram Positive (n = 2 /34%). Gram Negative was not predominantly isolated in the control group. CONCLUSION: No statistical significance was found between PBM-T alone and PBM-T + PDT. However, the better outcomes reached by PBM-T + PDT group would suggest there could be a role for combined treatment in the management of OM lesions.

Tooth extraction prior to radiotherapy for oropharyngeal cancer increases the risk of osteoradionecrosis.

PURPOSE: Osteoradionecrosis of the jaw is a therapy-resistant condition that may occur after treatment for head and neck cancer. The aim of this study was to investigate the incidence of osteoradionecrosis in patients with oropharyngeal cancer in relation to tooth extraction prior to radiation therapy. METHODS: Patients who had undergone radiation therapy for oropharyngeal cancer 5-10 years earlier were included and evaluated for the development of osteoradionecrosis (n = 75). RESULTS: Among the 75 patients, 62 had molar teeth present in the >50 Gy radiation field and 36 of those patients had teeth extracted prior to radiation therapy. Extraction of molars before radiotherapy significantly increased the risk of developing osteoradionecrosis (P < 0.05). There were no identifiable statistically significant correlations between the time from tooth extraction and the start of radiation therapy, the number of teeth in the radiation field, smoking habits, human papillomavirus-status, gender, age or tumor location and the development of osteoradionecrosis. CONCLUSION: Tooth extraction prior to radiation therapy increases the risk of developing osteoradionecrosis. For patients with good oral hygiene and absence of dental disease, avoidance of tooth extraction in the radiation field could therefore reduce the risk of complications.

Bacterial epiglottitis superimposed on oropharyngeal cancer: A case report.

BACKGROUND: Patients undergoing chemotherapy and radiotherapy are placed in an immunocompromised state worth consideration in the event of potential airway compromise, especially when superimposed on an airway-obstructing tumor. We report a case of bacterial epiglottitis in a patient with active oropharyngeal cancer (OPC), who presented in such a way that an infectious etiology was not initially considered in the patient's care. To our knowledge, such a circumstance has not been reported in the literature. CASE: Here, we report a case of a 68-year-old male with advanced-stage OPC who developed respiratory distress and underwent emergent tracheostomy. The patient was diagnosed postoperatively with Haemophilus influenza and Pseudomonas aerugeniosa. Following antibiotic treatment, the patient recovered to the point in which he could then undergo concomitant chemoradiation. The patient later had a recurrence of P. aerugeniosa during their radiotherapy that was also treated with antibiotics. The patient experienced continued symptoms related to their OPC and underwent pharyngectomy. Despite the initial success of this procedure, the patient experienced tumor recurrence and succumbed to his disease. CONCLUSION: This case underscores the importance of considering multiple etiologies concerning airway compromise, as the consequence of delayed cancer treatment may be loss of local cancer control.

Temporal Trends in Clinician-Assessed and Patient-Reported Swallowing Outcomes in Oropharyngeal Cancer Patients.

BACKGROUND: Dysphagia is a consequence of oropharyngeal squamous cell carcinoma (OPSCC) treatments and often results in a devastating reduction in quality of life (QoL; Nguyen et al., 2005; Pauloski, 2008). OBJECTIVES: This study aimed to report temporal trends in swallowing outcomes using the Modified Barium Swallow Impairment Profile (MBSImP) and the M.D. Anderson Dysphagia Inventory (MDADI) and to study the relationship between these two measures. METHOD: This was a retrospective review of clinical data collected in January 2013 to December 2017 from a tertiary care center. MBSImP PI scores and MDADI composite scores were collected pretreatment and 1, 6, and 12 months posttreatment. Data were analyzed in aggregate and stratified by treatment modality. To address the primary objective, descriptive statistics were used. To address the secondary objective, four Spearman tests were run between MBSImP PI and MDADI composite scores. RESULTS: A total of 123 OPSCC participants were included. With respect to trends, MBSImP PI scores worsened 1 month posttreatment and remained impaired at 6 and 12 months. For MDADI composite scores, patient reports worsened 1 month posttreatment and subsequently improved at 6 and 12 months. MBSImP PI and MDADI composite scores were weakly negatively correlated (i.e., in agreement) at the pre- and 12-month posttreatment appointments. CONCLUSIONS: Swallowing outcomes in OPSCC patients have distinct yet predictable trends for both clinician-assessed and patient-reported swallowing outcomes during the first year following cancer treatment. However, unlike previous findings, these two types of measures were in agreement at the pretreatment and 12 months posttreatment appointments.

[Infection of human papillomavirus and head and neck cancer].

High-risk human papillomavirus (HPV)-related cancers consist of cervical cancer, anal cancer, penile cancer, vulvar cancer, vaginal cancer, and head and neck cancer (HNC). Of these, the disease burden of HNC is second only to cervical cancer. HNC mostly originates from malignant lesions of squamous epithelial cells and mainly includes oral cavity cancer, pharyngeal cancer (including nasopharyngeal cancer, oropharyngeal cancer, and hypopharyngeal cancer), and laryngeal cancer. Tobacco use, alcohol abuse, and HPV infection are three primary risk factors. Recently, there is an upward trend of HNC incidence globally, especially in high-income countries. In China, the disease burden and trends of HPV-related HNC are still not clear. A few small sample size and single-center studies suggest a high HPV prevalence and increasing trend in HNC. Methodological differences in HPV testing and regional variabilities still exist among these studies. Among the anatomic sites, oropharyngeal cancer has been shown to be caused by HPV infection, but the association of HPV with other sites is still under debate. In addition, there is a paucity of relevant studies. Here, this review narrates the association between HPV infection and HNC, compares the differences between global and Chinese studies, and then explores the importance of HPV infection in various anatomical sites. The main objective is to highlight the research on HPV-related HNC and promote relevant prevention and treatment programs.

Transoral robotic surgery in a modified Trendelenburg position for oropharyngeal squamous cell carcinoma in a patient with severe thoracic kyphosis.

BACKGROUND: Excessive flexion of the neck and upper back from severe kyphosis of the thoracic spine may limit treatment options for head and neck cancer (HNC). METHODS: We describe an innovative approach to transoral robotic surgery (TORS) in a patient with severe thoracic kyphosis and oropharyngeal squamous cell carcinoma (OPSCC) who was unsuitable for definitive radiotherapy. RESULTS: Detailed discussion of management pathway, perioperative considerations, and surgical challenges is presented. TORS lateral oropharyngectomy was successfully performed with the robotic system docked from the caudal end in a modified Trendelenburg position. CONCLUSIONS: With appropriate surgical and anesthetic planning, TORS for patients with severe thoracic kyphosis is a feasible and suitable treatment.

Immunogenetic Determinants of Susceptibility to Head and Neck Cancer in the Million Veteran Program Cohort.

Increasing rates of human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) have largely offset declines in tobacco-associated head and neck squamous cell carcinoma (HNSCC) at non-OPC sites. Host immunity is an important modulator of HPV infection, persistence, and clearance, and also of immune evasion in both virally- and nonvirally-driven cancers. However, the association between collective known cancer-related immune gene variants and HNSCC susceptibility has not been fully characterized. Here, we conducted a genetic association study in the multiethnic Veterans Affairs Million Veteran Program cohort, evaluating 16,050 variants in 1,576 immune genes in 4,012 HNSCC cases (OPC = 1,823; non-OPC = 2,189) and 16,048 matched controls. Significant polymorphisms were further examined in a non-Hispanic white (NHW) validation cohort (OPC = 1,206; non-OPC = 955; controls = 4,507). For overall HNSCC susceptibility in NHWs, we discovered and validated a novel 9q31.1 SMC2 association and replicated the known 6p21.32 HLA-DQ-DR association. Six loci/genes for overall HNSCC susceptibility were selectively enriched in African-Americans (6p21.32 HLA-G, 9q21.33 GAS1, 11q12.2 CD6, 11q23.2 NCAM1/CD56, 17p13.1 CD68, 18q22.2 SOCS6); all 6 genes function in antigen-presenting regulation and T-cell activation. Two additional loci (10q26 DMBT1, 15q22.2 TPM1) were uncovered for non-OPC susceptibility, and three loci (11q24 CRTAM, 16q21 CDH5, 18q12.1 CDH2) were identified for HPV-positive OPC susceptibility. This study underscores the role of immune gene variants in modulating susceptibility for both HPV-driven and non-HPV-driven HNSCC. Additional large studies, particularly in racially diverse populations, are needed to further validate the associations and to help elucidate other potential immune factors and mechanisms that may underlie HNSCC risk. SIGNIFICANCE: Several inherited variations in immune system genes are significantly associated with susceptibility to head and neck cancer, which could help improve personalized cancer risk estimates.

Analysis of a hit-and-run tumor model by HPV in oropharyngeal cancers.

Several viruses are known to be associated with the development of certain cancers, including human papilloma virus (HPV), an established causative agent for a range of anogenital and head and neck cancers. However, the causality has been based on the presence of the virus, or its genetic material, in the sampled tumors. We have long wondered if viruses cause cancer via a "hit and run" mechanism such that they are no longer present in the resulting tumors. Here, we hypothesize that the absence of viral genes from the tumor does not necessarily exclude the viral aetiology. To test this, we used an HPV-driven oropharyngeal cancer (OPC) tumor model and CRISPR to delete the viral oncogene, E7. Indeed, the genetic removal of HPV E7 oncogene eliminates tumors in vivo. Remarkably, E7 deleted tumors recurred over time and develop new mutations not previously seen in HPV+ OPC tumors. Importantly, a number of these new mutations are found to be already present in HPV- OPC tumors.

Association of hearing loss and tinnitus symptoms with health-related quality of life among long-term oropharyngeal cancer survivors.

BACKGROUND: This study investigated the association of hearing loss and tinnitus with overall health-related quality of life (HRQoL) among long-term oropharyngeal cancer (OPC) survivors. METHODS: This study included OPC survivors treated between 2000 and 2013 and surveyed from September 2015 to July 2016. Hearing loss and tinnitus were measured by asking survivors to rate their "difficulty with hearing loss and/or ringing in the ears" from 0 (not present) to 10 (as bad as you can imagine). Hearing loss and tinnitus scores were categorized as follows: 0 for none, 1-4 for mild, and 5-10 for moderate to severe. The primary outcome was the mean score of MD nderson Symptom Inventory Head & Neck module interference component as a HRQoL surrogate dichotomized as follows: 0 to 4 for none to mild and 5 to 10 for moderate to severe interference. RESULTS: Among 880 OPC survivors, 35.6% (314), reported none, 39.3% (347) reported mild, and 25.1% (221) reported moderate to severe hearing loss and tinnitus. On multivariable analysis, mild (OR, 5.83; 95% CI; 1.48-22.88; p = 0.012) and moderate (OR, 30.01; 95% CI; 7.96-113.10; p < 0.001) hearing loss and tinnitus were associated with higher odds of reporting moderate to severe symptom interference scores in comparison to no hearing loss and tinnitus. This association of hearing dysfunction was consistent with all domains of HRQoL. CONCLUSIONS: Our findings provide preliminary evidence to support the need for continued audiological evaluations and surveillance to detect hearing dysfunction, to allow for early management and to alleviate the long-term impact on QoL.

Successful Hypoglossal Nerve Upper Airway Stimulator Implantation After Chemoradiotherapy for Oropharynx Malignancy Complicated by Mandibular Osteoradionecrosis.

This case demonstrates the first successful treatment of obstructive sleep apnea with hypoglossal nerve upper airway stimulation in a patient with prior radiation for oropharynx cancer complicated by osteoradionecrosis of the mandible.

Acute Swallowing Outcomes After Surgical Resection of Oral Cavity and Oropharyngeal Cancers With the Mandibular Lingual Release Approach.

OBJECTIVE: To investigate the incidence, nature, severity, and recovery of early dysphagia in patients following surgical resection of oral and/or oropharyngeal squamous cell carcinoma with a mandibular lingual release approach (MLRA). STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary head and neck cancer center. METHODS: Inclusion of patients' after surgical resection of oral cavity and/or oropharyngeal squamous cell carcinoma via an MLRA between 2012 and 2017. Data collection included acute medical care, enteral feeding, and swallowing outcomes derived from clinical swallow examination and videofluoroscopic swallowing study assessments at baseline, after surgery, and prior to discharge. RESULTS: Twenty-eight patients were eligible for participation (23 males; mean age, 63 years). Baseline clinical swallow examination findings revealed that 32% (n = 9) were tolerating normal diet and fluids preoperatively (Functional Oral Intake Scale [FOIS] = 7). Following surgery, the majority (n = 21, 75%) experienced severe dysphagia (FOIS ≤4), of which 15 were nil by mouth. Twelve patients received a postoperative videofluoroscopic swallowing study, with silent aspiration observed in 9 cases. At discharge, 12 (43%) patients had persistent severe functional dysphagia (FOIS ≤4) with ongoing enteral feeding requirements, of which 7 were nil by mouth. Eleven (39%) were managing diets of modified fluid/diet consistencies (FOIS = 5), and 5 (18%) had mild dysphagia (FOIS ≥6) at discharge. None were able to manage a normal diet. The average length of hospital stay was 27.9 days. CONCLUSIONS: Early dysphagia post-MLRA is a common and often severe complication of surgery. Patients require extended hospital admission with prolonged enteral feeding, which may persist postdischarge. This cohort requires early intervention by speech-language pathology services to aid swallow rehabilitation.

Does Human Papillomavirus Infection Influence the Frequency and Severity of Nutritional Disorders in Head and Neck Cancer?

BACKGROUND: About 87% of head and neck cancer (HNC) patients (mostly oropharyngeal cancer-OPC) are infected with human papillomavirus (HPV). Recent studies have demonstrated a significant correlation between HPV infection and nutritional disorders in HNC patients. Therefore, we formed a hypothesis that nutritional disorders or their severity in HNC patients may be associated with the occurrence of HPV infection due to known molecular differences in involved tissue. This literature review aimed to evaluate the influence of HPV infection on the occurrence and severity of nutritional disorders in HNC patients. MATERIALS AND METHODS: The PubMed database was used to search papers with the keywords "HPV", "HNC", and "nutritional disorders" in different variants and combinations. CONCLUSIONS: The data available in the discussed papers indicate, among other things, that HPV-positive patients may be at higher risk of malnutrition, critical weight loss, and necessity for gastrostomy after radiotherapy or chemoradiotherapy (C-RT). It should be highlighted that despite some studies demonstrating positive results, currently available data regarding the influence of HPV infection on the occurrence and severity of nutritional disorders in HNC remain limited and inconclusive, and thus further research on this issue is warranted.