Consensuses, controversies, and future directions in treatment deintensification for human papillomavirus-associated oropharyngeal cancer.

The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long-term morbidities with chemoradiation and the favorable prognosis of HPV-positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head-and-neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de-escalation. National database studies estimate that up to one third of patients receive nonstandard de-escalated treatments, which have subspecialty-specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV-positive OPC de-escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de-escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy-based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de-escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real-time surveillance.

Association of human papillomavirus genotype and phylogenic clade with oropharyngeal cancer outcomes.

BACKGROUND: Human papillomavirus (HPV)+ oropharynx cancer (OPC) has a more favorable prognosis than HPV-negative disease, but the impact of specific HPV genotype and phylogenic clade on patient outcomes is not well understood and has profound implications for treatment de-intensification. METHODS: The objective of this single-institution cohort study was to investigate the association of HPV genotype (16 vs high-risk non-16) and clade (A9 vs A7) with OPC outcomes. The primary endpoints were overall survival (OS) and event-free survival (EFS) in patients with M0 disease treated with curative intent. RESULTS: The cohort included 598 patients (87% HPV16, 98% A9). Compared to those with HPV16 OPC, individuals with non-HPV16 OPC had a higher age, comorbidity index, and proportion of non-whites, HIV+ patients, T4 tumors, and stage IV disease (AJCC 7th edition). Non-HPV16 genotype was associated with worse OS in univariate (HR = 2.17, 95% CI, 1.24-3.80, P = .0066), but not in multivariate analysis (HRadj = 0.84, 95% CI, 0.43-1.62, P = .5921). A7 clade was associated with worse OS in univariate (HR = 4.42, 95% CI, 1.60-12.30, P = .0041), but not in multivariate analysis (HRadj = 2.39, 95% CI, 0.57-9.99, P = .2325). Neither HPV genotype (HR = 1.60, 95% CI, 0.99-2.60, P = .0566) nor phylogenic clade (HR = 2.47, 95% CI, 0.91-6.72, P = .0761) was associated with EFS. CONCLUSION: Non-HPV16 genotype and A7 clade were associated with worse OS and trended toward worse EFS in univariate analyses. The survival differences were more pronounced by phylogenic clade than by HPV16 status, suggesting that the former may be a more useful classification for future studies. However, neither HPV16 status nor phylogenic clade was prognostic when adjusting for patient and tumor covariates, raising the question as to whether possible differences in outcomes are related to distinct clinical profiles rather than inherent viral properties.

Deep learning-based multimodal segmentation of oropharyngeal squamous cell carcinoma on CT and MRI using self-configuring nnU-Net.

PURPOSE: To evaluate deep learning-based segmentation models for oropharyngeal squamous cell carcinoma (OPSCC) using CT and MRI with nnU-Net. METHODS: This single-center retrospective study included 91 patients with OPSCC. The patients were grouped into the development (n = 56), test 1 (n = 13), and test 2 (n = 22) cohorts. In the development cohort, OPSCC was manually segmented on CT, MR, and co-registered CT-MR images, which served as the ground truth. The multimodal and multichannel input images were then trained using a self-configuring nnU-Net. For evaluation metrics, dice similarity coefficient (DSC) and mean Hausdorff distance (HD) were calculated for test cohorts. Pearson's correlation and Bland-Altman analyses were performed between ground truth and prediction volumes. Intraclass correlation coefficients (ICCs) of radiomic features were calculated for reproducibility assessment. RESULTS: All models achieved robust segmentation performances with DSC of 0.64 ± 0.33 (CT), 0.67 ± 0.27 (MR), and 0.65 ± 0.29 (CT-MR) in test cohort 1 and 0.57 ± 0.31 (CT), 0.77 ± 0.08 (MR), and 0.73 ± 0.18 (CT-MR) in test cohort 2. No significant differences were found in DSC among the models. HD of CT-MR (1.57 ± 1.06 mm) and MR models (1.36 ± 0.61 mm) were significantly lower than that of the CT model (3.48 ± 5.0 mm) (p = 0.037 and p = 0.014, respectively). The correlation coefficients between the ground truth and prediction volumes for CT, MR, and CT-MR models were 0.88, 0.93, and 0.9, respectively. MR models demonstrated excellent mean ICCs of radiomic features (0.91-0.93). CONCLUSION: The self-configuring nnU-Net demonstrated reliable and accurate segmentation of OPSCC on CT and MRI. The multimodal CT-MR model showed promising results for the simultaneous segmentation on CT and MRI. CLINICAL RELEVANCE STATEMENT: Deep learning-based automatic detection and segmentation of oropharyngeal squamous cell carcinoma on pre-treatment CT and MRI would facilitate radiologic response assessment and radiotherapy planning. KEY POINTS: • The nnU-Net framework produced a reliable and accurate segmentation of OPSCC on CT and MRI. • MR and CT-MR models showed higher DSC and lower Hausdorff distance than the CT model. • Correlation coefficients between the ground truth and predicted segmentation volumes were high in all the three models.

Patterns of recurrence in head and neck squamous cell carcinoma to inform personalized surveillance protocols.

BACKGROUND: Development of evidence-based post-treatment surveillance guidelines in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is limited by comprehensive documentation of patterns of recurrence and metastatic spread. METHODS: A retrospective analysis of patients diagnosed with R/M HNSCC at a National Cancer Institute-designated cancer center between 1998- 2019 was performed (n = 447). Univariate and multivariate analysis identified patterns of recurrence and predictors of survival. RESULTS: Median overall survival (mOS) improved over time (6.7 months in 1998-2007 to 11.8 months in 2008-2019, p = .006). Predictors of worse mOS included human papillomavirus (HPV) negativity (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.2-2.6), high neutrophil/lymphocyte ratio (HR, 2.1 [1.4-3.0], disease-free interval (DFI) ≤6 months (HR, 1.4 [1.02-2.0]), and poor performance status (Eastern Cooperative Oncology Group, ≥2; HR, 1.91.1-3.4). In this cohort, 50.6% of recurrences occurred within 6 months of treatment completion, 72.5% occurred within 1 year, and 88.6% occurred within 2 years. Metachronous distant metastases were more likely to occur in patients with HPV-positive disease (odds ratio [OR], 2.3 [1.4-4.0]), DFI >6 months (OR, 2.4 [1.5-4.0]), and body mass index ≥30 (OR, 2.3 [1.1-4.8]). Oligometastatic disease treated with local ablative therapy was associated with improved survival over polymetastatic disease (HR, 0.36; 95% CI, 0.24-0.55). CONCLUSION: These data regarding patterns of distant metastasis in HNSCC support the clinical utility of early detection of recurrence. Patterns of recurrence in this population can be used to inform individualized surveillance programs as well as to risk-stratify eligible patients for clinical trials. PLAIN LANGUAGE SUMMARY: After treatment for head and neck cancer (HNC), patients are at risk of recurrence at prior sites of disease or at distant sites in the body. This study includes a large group of patients with recurrent or metastatic HNC and examines factors associated with survival outcomes and recurrence patterns. Patients with human papillomavirus (HPV)-positive HNC have good survival outcomes, but if they recur, this may be in distant regions of the body and may occur later than HPV-negative patients. These data argue for personalized follow-up schedules for patients with HNC, perhaps incorporating imaging studies or novel blood tests.

Analysis of cells of epithelial, connective tissue and immune differentiation in HPV-positive-, HPV-negative oropharyngeal carcinoma and normal oropharyngeal tissue by immunofluorescence multiplex image cytometry: a preliminary report.

BACKGROUND: Epithelial, connective tissue and immune cells contribute in various ways to the pathophysiology of HPV positive (HPV+) and HPV negative (HPV-) oropharyngeal squamous cell carcinoma (OPSCC). We aimed to investigate the abundance of these cell lineages and their coexpression patterns in patients with HPV + and HPV- OPSCC. METHODS: We used a 4-channel immunofluorescence-microscopy technique for the simultaneous detection of three direct-conjugated antibodies (pancytokeratin, vimentin and CD45/CD18) and DAPI (4',6-Diamidin-2-phenylindole) in formalin fixed paraffin-embedded tissue samples (FFPE) of patients with HPV + and HPV- OPSCC, and of control patients. Image acquisition and analysis were performed with TissueFAXS and StrataQuest (TissueGnostics, Vienna, Austria), respectively, in tumor cell clusters/stroma in OPSCC specimens and epithelial layer/lamina propria in control specimens. Cell populations were created based on antibodies' coexpression patterns. Isotype and positive controls were examined for plausibility. RESULTS: The proportion of cells of epithelial differentiation in tumor cell clusters was higher in HPV + OPSCC (55%) than in HPV- OPSCC samples (44%). The proportion of connective tissue cells in tumor cell cluster was lower in HPV + OPSCC patients (18%) than in HPV- OPSCC patients (26%). The proportion of immune cells in tumor cell clusters was higher in HPV + OPSCC patients (25%) than in HPV- OPSCC patients (18%). The percentage of anaplastic, potentially de-differentiated cells, was 2% in control patients, and it was higher in HPV- OPSCC (21%) than in HPV + OPSCC samples (6%). CONCLUSIONS: This study provided the first quantitative data for the abundance of cells of epithelial, connective tissue and immune differentiation, in patients with OPSCC and control patients. The abundance of these different crucial cell populations was consistently originating from the same tissue sample. De-differentiation of tumor cells was higher in HPV- OPSCC than in HPV + OPSCC. In tumor cells clusters, the antitumoral host immune response was higher in HPV + OPSCC than in HPV- OPSCC, whereas the fibroblast response was higher in HPV- OPSCC than in HPV + OPSCC. This study contributed to the understanding of histopathologic differences between HPV + OPSCC and HPV- OPSCC patients.

External validation of an MR-based radiomic model predictive of locoregional control in oropharyngeal cancer.

OBJECTIVES: To externally validate a pre-treatment MR-based radiomics model predictive of locoregional control in oropharyngeal squamous cell carcinoma (OPSCC) and to assess the impact of differences between datasets on the predictive performance. METHODS: Radiomic features, as defined in our previously published radiomics model, were extracted from the primary tumor volumes of 157 OPSCC patients in a different institute. The developed radiomics model was validated using this cohort. Additionally, parameters influencing performance, such as patient subgroups, MRI acquisition, and post-processing steps on prediction performance will be investigated. For this analysis, matched subgroups (based on human papillomavirus (HPV) status of the tumor, T-stage, and tumor subsite) and a subgroup with only patients with 4-mm slice thickness were studied. Also the influence of harmonization techniques (ComBat harmonization, quantile normalization) and the impact of feature stability across observers and centers were studied. Model performances were assessed by area under the curve (AUC), sensitivity, and specificity. RESULTS: Performance of the published model (AUC/sensitivity/specificity: 0.74/0.75/0.60) drops when applied on the validation cohort (AUC/sensitivity/specificity: 0.64/0.68/0.60). The performance of the full validation cohort improves slightly when the model is validated using a patient group with comparable HPV status of the tumor (AUC/sensitivity/specificity: 0.68/0.74/0.60), using patients acquired with a slice thickness of 4 mm (AUC/sensitivity/specificity: 0.67/0.73/0.57), or when quantile harmonization was performed (AUC/sensitivity/specificity: 0.66/0.69/0.60). CONCLUSION: The previously published model shows its generalizability and can be applied on data acquired from different vendors and protocols. Harmonization techniques and subgroup definition influence performance of predictive radiomics models. KEY POINTS: • Radiomics, a noninvasive quantitative image analysis technique, can support the radiologist by enhancing diagnostic accuracy and/or treatment decision-making. • A previously published model shows its generalizability and could be applied on data acquired from different vendors and protocols.

Use of tongue base palpation among oral healthcare providers: Cross-sectional survey.

OBJECTIVES: To assess the use of tongue base palpation during cancer screening exams by Oral Healthcare Providers (OHPs) and explore attitudes about (1) the usefulness of oral cancer screening (OCS) in detecting early, asymptomatic lesions and (2) routine OCS of the general population. STUDY DESIGN: Survey study. SETTING: Private and hospital-based clinical practices of OHPs located in Massachusetts and Connecticut, United States. METHODS: An anonymous, online 9-item survey assessing beliefs and practice patterns about cancer screening exams was distributed to OHPs with practices in Massachusetts and Connecticut from August 2020 to June 2021. Data were analyzed using chi-square tests and Pearson correlations. Statistically significant levels were established at P < .050. RESULTS: One hundred seventy-one responses were analyzed (response rate 17 %). Tongue base palpation was performed as part of a routine cancer screening exam by 55 % of otolaryngologists, 34 % of dentists and 29 % of OMFS (P = .030). Providers who palpated the tongue base were also more likely to use palpation as an exam technique in the tonsils (r = 0.52 [95 % CI 0.40-0.62]; P < .001) among other intra-and extra-oral anatomical subsites. Almost all dentists (92 %) and OMFS (98 %) but only 58 % of otolaryngologists considered OCS useful for detection of early, asymptomatic malignant lesions in the oral cavity (P < .001). CONCLUSIONS: While tongue base palpation can detect oropharyngeal cancers in a pre-symptomatic stage, it is underutilized during routine cancer screening exams. Considering the rising incidence of oropharyngeal cancer, tongue base palpation should be established as a routine part of cancer screening by OHPs.

Global prevalence of human papillomavirus-related oral and oropharyngeal squamous cell carcinomas: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review to determine the global prevalence of HPV in oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: Literature was searched through October 2022 in main databases to address the question "What is the global prevalence of Human Papillomavirus in oral and oropharyngeal cancer?" Studies had to identify HPV by PCR, ISH, or p16 immunohistochemistry to be eligible. Quality was assessed using the JBI checklist for prevalence studies. Meta-analyses were performed, and reporting followed PRISMA guidelines. RESULTS: Sixty-five studies were included, and most of them had methodological limitations related to sampling and the HPV detection tool. The pooled prevalence of HPV-positivity was 10% (event rate = 0.1; 95% CI: 0.07, 0.13; P < 0.01; I2 = 88%) in the oral cavity and 42% (event rate = 0.42; 95% CI: 0.36, 0.49; P = 0.02; I2 = 97%) in oropharynx. The highest HPV prevalence in OSCC was reached by Japan, meanwhile, in OPSCC, Finland and Sweden were the most prevalent. HPV16 is the genotype most frequent with 69% in OSCC and 89% in OPSCC, being the tonsils the intraoral location more affected by HPV (63%, p < 0.01, I2 76%). CONCLUSION: The evidence points to an apparent burden in HPV-related OPSCC, mostly in North America, Northern Europe, and Oceania, especially due to the HPV16 infection suggesting different trends across continents. CLINICAL RELEVANCE: This updated systematic review and meta-analysis provide sufficient evidence about the global HPV prevalence in OSCC and OPSCC and the most frequent HPV subtype worldwide.

[Data from the 2022 ASCO Annual Meeting on surgical therapy]. / Daten vom ASCO-Kongress 2022 zum Thema "chirurgische Therapie".

Last year, studies on immuno-oncologic treatment approaches for recurrent or metastatic head and neck cancer were the main focus at the two major international cancer congresses of the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO). The success of these therapeutic strategies has led to many new studies, including their use in the neoadjuvant setting. This review article summarizes presented studies from ASCO 2022 in which surgical therapy is the focus of the study protocol and also includes study results on neoadjuvant treatment strategies. No surgical trials were presented at ESMO 2022. At ASCO 2022 as well as in previous years, it became increasingly clear that treatment de-escalation in the context of human papillomavirus (HPV)-associated oropharyngeal carcinoma treatment involving surgical measures appears to be oncologically safe and functionally beneficial. In addition, a number of studies indicate that in the setting of neoadjuvant administration of immuno-oncologic agents, a proportion of patients have pathologic complete remission. In this fraction of patients, which is usually significantly smaller than 50%, survival data are better than in those who have already failed to respond to neoadjuvant therapy. Unfortunately, however, significant toxicities or tumor progression with the risk of inoperability were also seen under these current therapeutic regimens, leading to discontinuation of therapy in 5-20% of cases. It remains to be seen whether neoadjuvancy with immune checkpoint inhibitors can establish itself, in contrast to the failed attempts of the past with the use of cytostatics.

Outcomes of Oral and Oropharyngeal Squamous Cell Carcinoma Related to Healthcare Coverage: A Retrospective Cohort Study in Brazil.

We investigated the differences in prognosis according to the type of healthcare coverage of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). This study included 875 medical records. Patients covered by the publicly funded Unified Health System (SUS) had a low educational level, with advanced T stage and delayed treatment initiation. Multivariate analyses revealed an association between T stage (p = .035) and poor prognosis in oral squamous cell carcinoma, and age (p = .029) in oropharyngeal squamous cell carcinoma. Surgical treatment (p = .036) and marital status (p = .015) were considered predictors of better prognosis in OOSCC. Exclusive SUS-dependency can be considered an indirect prognostic factor for OOSCC.

2011-2021 rising prevalence of HPV infection among oropharyngeal carcinoma in France.

BACKGROUND: The objective of our study was to investigate changes over the past decade in patient age and the prevalence of HPV in the population of patients with oropharyngeal carcinoma (OPC) treated at our center. METHODS: We performed a retrospective cohort study of patients treated at our cancer center for OPC between 2011 and 2021. Tissue biopsies were assessed for HPV status based on p16 staining for all patients. RESULTS: There were 1,365 treated patients. The proportion of p16-positive patients increased from 43% in 2011 to 57.3% in 2021 (p = 0.01). The sex ratio was 3.6 M/1F for p16-positive and 3.7 M/1F for p16-negative patients (p = 0.94). The mean age increased from 60.2 y in 2011 to 63.6 y in 2021. The mean ages were 61.9 y for p16-positive and 61.7 y for p16-negative patients (p = 0.71), but there was a broader age distribution for the p16-positive patients (p = 0.03). The proportion of patients older than 70 y increased from 11% in 2011 to 28.2% in 2021, and this aging was similar between p16-positive (30.7% in 2021) and p16-negative (26.3% in 2021) patients. The 2-year and 5-year OS rates were 73.7% and 56.5% for the entire cohort. p16-positive patients had 2-year and 5-year OS rates of 86.8% and 77.4%, respectively, whereas p16-negative patients had 2-year and 5-year OS rates of 63.9% and 40.5%. CONCLUSIONS: Assessment of the change over the past decade in the population of patients with OPC at our center showed that HPV-positive OPC now appear to have overtaken HPV-negative cases in France, with 57.3% in 2021, and showed significant aging, with almost thirty percent of patients now older than 70 years. Those combined changes emphasize some of the challenges to be addressed in future OPC management.

The impact of radiomics for human papillomavirus status prediction in oropharyngeal cancer: systematic review and radiomics quality score assessment.

PURPOSE: Human papillomavirus (HPV) status assessment is crucial for decision making in oropharyngeal cancer patients. In last years, several articles have been published investigating the possible role of radiomics in distinguishing HPV-positive from HPV-negative neoplasms. Aim of this review was to perform a systematic quality assessment of radiomic studies published on this topic. METHODS: Radiomics studies on HPV status prediction in oropharyngeal cancer patients were selected. The Radiomic Quality Score (RQS) was assessed by three readers to evaluate their methodological quality. In addition, possible correlations between RQS% and journal type, year of publication, impact factor, and journal rank were investigated. RESULTS: After the literature search, 19 articles were selected whose RQS median was 33% (range 0-42%). Overall, 16/19 studies included a well-documented imaging protocol, 13/19 demonstrated phenotypic differences, and all were compared with the current gold standard. No study included a public protocol, phantom study, or imaging at multiple time points. More than half (13/19) included feature selection and only 2 were comprehensive of non-radiomic features. Mean RQS was significantly higher in clinical journals. CONCLUSION: Radiomics has been proposed for oropharyngeal cancer HPV status assessment, with promising results. However, these are supported by low methodological quality investigations. Further studies with higher methodological quality, appropriate standardization, and greater attention to validation are necessary prior to clinical adoption.

The characteristics of missed pharyngeal and laryngeal cancers at gastrointestinal endoscopy.

OBJECTIVES: Understanding the miss rate and characteristics of missed pharyngeal and laryngeal cancers during upper gastrointestinal endoscopy may aid in reducing the endoscopic miss rate of this cancer type. However, little is known regarding the miss rate and characteristics of such cancers. Therefore, the aim of this study was to investigate the upper gastrointestinal endoscopic miss rate of oro-hypopharyngeal and laryngeal cancers, the characteristics of the missed cancers, and risk factors associated with the missed cancers. METHODS: Patients who underwent upper gastrointestinal endoscopy and were pathologically diagnosed with oro-hypopharyngeal and laryngeal squamous cell carcinoma from January 2019 to November 2020 at our institution were retrospectively evaluated. Missed cancers were defined as those diagnosed within 15 months after a negative upper gastrointestinal endoscopy. RESULTS: A total of 240 lesions were finally included. Eighty-five lesions were classified as missed cancers, and 155 lesions as non-missed cancers. The upper gastrointestinal endoscopic miss rate for oro-hypopharyngeal and laryngeal cancers was 35.4%. Multivariate analysis revealed that a tumor size of <13 mm (odds ratio: 1.96, P=0.026), tumors located on the anterior surface of the epiglottis/valleculae (odds ratio: 2.98, P=0.045) and inside of the pyriform sinus (odds ratio: 2.28, P=0.046) were associated with missed cancers. CONCLUSIONS: This study revealed a high miss rate of oro-hypopharyngeal and laryngeal cancers during endoscopic observations. High-quality upper gastrointestinal endoscopic observation and awareness of missed cancer may help reduce this rate.

Cytokeratin 7 and 19 expression in oropharyngeal and oral squamous cell carcinoma.

PURPOSE: The precise etiopathogenesis of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC), and reasons for predilection for crypt epithelium, remain uncertain. The purpose of this study is to investigate the interaction between HPV and specific cytokeratins 7 (CK7) and 19 (CK19) in crypt epithelium. METHODS: This is a retrospective cohort study of patients presenting between 1999 and 2015 at a tertiary referral center. CK7 and CK19 positivity and H Scores were determined by immunohistochemistry. Disease-specific and overall survival rates were analyzed. RESULTS: There were 253 patients presenting with OPSCC (134), squamous cell carcinoma (SCC) of unknown primary site (22), and oral tongue SCC (97). Primary tumor CK7 and CK19 positivity and H Scores were significantly higher in HPV-positive OPSCC than HPV-negative OPSCC and oral tongue SCC. Higher CK19 Scores, but not CK7 Scores, were also seen in regional metastases from HPV-positive OPSCC than other sites. No impact on disease-specific or overall survival was identified on multivariate analysis. CONCLUSION: The increased expression of CK7 and CK19 in HPV-positive OPSCC compared to HPV-negative disease supports the theory for a role for these cytokeratins in the etiopathogenesis of HPV-related OPSCC.

The impact of HPV vaccination on the prevention of oropharyngeal cancer: A scoping review.

INTRODUCTION: HPV-associated oropharyngeal cancer (OPC) has one of the most rapidly rising incidences of any cancer in high-income countries. HPV vaccination is being tested to prevent HPV-associated OPC. OBJECTIVE: To determine the effect of Human Papilloma Virus (HPV) vaccination on the prevention of OPC in adults worldwide. BASIC RESEARCH DESIGN: Scoping review conducted using PRISMA-ScR Checklist. METHOD: An electronic literature search identified relevant records. Titles and abstracts were screened to assess eligibility by two researchers, and data from relevant full-text articles were extracted and synthesised. RESULTS: Three-hundred-and-forty-three studies were identified, with eleven articles meeting the inclusion criteria. The most common study design was cross-sectional (n = 7), the most common location was the US (n = 6) and data collection periods spanned 2004 to 2020. One article found unvaccinated participants had a 19 times increased risk of developing OPC compared with those who had been vaccinated against HPV. The remaining papers showed that prevalence of HPV-vaccine-type oral infection was significantly lower in vaccinated participants than unvaccinated participants, with a reduction of oral HPV detection ranging from 72% to 93%. This reduction varied by sex. CONCLUSIONS: There is evidence to suggest that HPV vaccination reduces oral HPV infection and decreases the incidence of HPV-associated OPC. There is substantial need for further research which directly examines the relationship between HPV vaccination status and subsequent OPC development.

[Chemotherapy and targeted therapy of head and neck squamous cell carcinomas at the 2021 ASCO meeting]. / Chemotherapie und zielgerichtete Therapie von Kopf-Hals-Plattenepithelkarzinomen beim ASCO-Kongress 2021.

BACKGROUND: This article summarizes new findings on chemo- and targeted therapy of head and neck squamous cell carcinoma presented at the 2021 American Society of Clinical Oncology (ASCO) conference. OBJECTIVE: Relevant publications were evaluated and summarized. METHODS: The abstract database of the 2021 ASCO conference was searched. Publications were selected if they focused on chemo- or targeted therapies in head and neck squamous cell carcinoma. Publications covered in other articles of this issue were omitted, as were study proposals without results. RESULTS: The authors present six articles. Dosage and novel forms of application are shown for cisplatin. Cetuximab is used in the neoadjuvant setting and for progressive disease following immune therapy. Lastly, two new drugs in the form of liposomal irinotecan and the mHRAS inhibitor tipifarnib are discussed. CONCLUSION: Patient-specific and possibly local application of cisplatin might be considered in the future. Moreover, mHRAS inhibition might also be useful for selected patients after sequencing.

[New data on surgical therapy from the 2021 ASCO Annual Meeting]. / Neue Daten vom ASCO-Kongress 2021 zum Thema "chirurgische Therapie".

In addition to medical therapy studies and translational basic projects, surgically oriented studies are also regularly presented at the ASCO Annual Meeting. At the virtual conference in 2021, an US group presented a well-designed study on the de-escalation of adjuvant therapy after transoral robotic surgery of HPV-positive oropharyngeal cancer. Furthermore, the results of an Italian group on induction therapy for resectable sinunasal carcinomas were presented. An ongoing multicenter study on the surgical treatment of early-stage oral cavity cancer will investigate the impact of sentinel lymph node biopsy compared to elective neck dissection. In addition to these presentations, the following review article summarizes other studies in which surgical therapy was part of the investigational workflow.

Characteristics and in-hospital morbidity trends associated with oral and oropharyngeal cancers in Brazil.

BACKGROUND: Brazil experienced an expansion of the population's access to oral health policies after the creation of the Unified Health System (SUS, Sistema Único de Saúde). Through public policies, the consolidation of Primary Health Care (PHC) and the incorporation of dental care into primary and hospital care took place. The objective of this study was to identify epidemiological aspects, including the temporal trend, of hospital morbidity from oral and oropharyngeal cancer in Brazil, considering hospitalizations for this neoplasm in a hospital network linked to the public care system. METHODS: Observational study based on information on hospital admissions for oral cancer throughout Brazil. The research used data from the Brazilian Cancer Registry Information System. For the temporal series analysis, generalized linear regression model was used with the Prais-Winsten method. RESULTS: Of the 121,971 patients hospitalized with oral and oropharyngeal cancers, 76.40% were male and 23.60% were female, resulting in a M:F ratio of 3.24:1. Regarding the anatomical region of involvement among hospitalized patients with oral cavity neoplastic lesions, there was a predominance in non-specific places in the mouth, such as the floor of the mouth, soft and hard palate, among others (32.68%), followed by lesions in the region of tongue (28.89%). In this population, the predominant age group was between the fifth decade (31.09%) and sixth decade of life (24.99%); men presented neoplastic lesions of oral and oropharyngeal cancers at an earlier age than women. In all regions of the country, the staging of cases diagnosed in the tertiary health network accredited to the José Alencar Gomes da Silva National Cancer Institute (INCA) was late, with higher tendency for metastasis. The temporal trend of the adjusted in-hospital morbidity rates showed to be increasing in the Northeast, South and Midwest regions for the male gender. For females, they were increasing in the Northeast and South regions. CONCLUSIONS: It is concluded that the distribution of in-hospital morbidity rates of oral and oropharyngeal cancers in the country is irregular. There is a greater number of cases identified by the study in male patients and in the Southeast and South regions; with an increasing tendency of this coefficient in both genders.

Timing, number, and type of sexual partners associated with risk of oropharyngeal cancer.

BACKGROUND: Case-control studies from the early 2000s demonstrated that human papillomavirus-related oropharyngeal cancer (HPV-OPC) is a distinct entity associated with number of oral sex partners. Using contemporary data, we investigated novel risk factors (sexual debut behaviors, exposure intensity, and relationship dynamics) and serological markers on odds of HPV-OPC. METHODS: HPV-OPC patients and frequency-matched controls were enrolled in a multicenter study from 2013 to 2018. Participants completed a behavioral survey. Characteristics were compared using a chi-square test for categorical variables and a t test for continuous variables. Adjusted odds ratios (aOR) were calculated using logistic regression. RESULTS: A total of 163 HPV-OPC patients and 345 controls were included. Lifetime number of oral sex partners was associated with significantly increased odds of HPV-OPC (>10 partners: odds ratio [OR], 4.3 [95% CI, 2.8-6.7]). After adjustment for number of oral sex partners and smoking, younger age at first oral sex (<18 vs >20 years: aOR, 1.8 [95% CI, 1.1-3.2]) and oral sex intensity (>5 sex-years: aOR, 2.8 [95% CI, 1.1-7.5]) remained associated with significantly increased odds of HPV-OPC. Type of sexual partner such as older partners when a case was younger (OR, 1.7 [95% CI, 1.1-2.6]) or having a partner who had extramarital sex (OR, 1.6 [95% CI, 1.1-2.4]) was associated with HPV-OPC. Seropositivity for antibodies to HPV16 E6 (OR, 286 [95% CI, 122-670]) and any HPV16 E protein (E1, E2, E6, E7; OR, 163 [95% CI, 70-378]) was associated with increased odds of HPV-OPC. CONCLUSION: Number of oral sex partners remains a strong risk factor for HPV-OPC; however, timing and intensity of oral sex are novel independent risk factors. These behaviors suggest additional nuances of how and why some individuals develop HPV-OPC.

The diagnostic performance of CT and MRI for detecting extranodal extension in patients with head and neck squamous cell carcinoma: a systematic review and diagnostic meta-analysis.

OBJECTIVE: To review the diagnostic performance of CT and MRI for detecting extranodal extension (ENE) in head and neck squamous cell carcinoma (HNSCC) patients. METHODS: MEDLINE and EMBASE databases were searched up to October 7, 2019. Studies that evaluated the diagnostic performance of CT and/or MRI for detecting ENE in HNSCC patients were included. A 2 × 2 table was reconstructed for each study. Pooled sensitivity and specificity were calculated using the bivariate model and hierarchical summary receiver operating characteristic (HSROC) model. Subgroup analyses were performed according to HPV status and radiological features. Pooled correlation coefficient for interobserver agreement was calculated. RESULTS: Twenty-two studies including 2478 patients were included. The pooled sensitivity and specificity for detecting ENE were 73% (95% CI, 62-82%) and 83% (95% CI, 75-89%), respectively, for CT, and 60% (95% CI, 49-70%) and 96% (95% CI, 85-99%), respectively, for MRI. There was substantial heterogeneity for both CT and MRI. A threshold effect was present for MRI. On subgroup analysis, the pooled specificity of CT was significantly lower in patients with HPV+ OPSCC than in patients with HPV­ oral cavity cancer or all HNSCC (74% vs. 87%; p = 0.01). Central node necrosis showed significantly higher pooled sensitivity (81% vs. 51%; p = 0.02), while infiltration of adjacent planes showed significantly higher pooled specificity (94% vs. 65%; p = 0.03). The pooled correlation coefficient was 0.72 (95% CI, 0.60-0.81). CONCLUSION: Both CT and MRI show reasonable diagnostic performance for detecting ENE in HNSCC patients and interobserver agreement was substantial. KEY POINTS: • Pooled sensitivity and specificity were 73% and 83% for CT and 60% and 96% for MRI without significant difference. • Pooled specificity was lower for HPV+ OPSCC than for HPV­ oral cavity cancer or all HNSCC (74% vs. 87%, p = 0.01), likely due to central node necrosis. • Central node necrosis showed higher sensitivity (81% vs. 51%; p = 0.02), while infiltration of adjacent planes showed higher specificity (94% vs. 65%; p = 0.03).