HPV-related Oropharyngeal Carcinoma Research Articles

Circulating tumour HPV16 DNA quantification – A prognostic tool for progression-free survival in patients with HPV-related oropharyngeal carcinoma receiving curative chemoradiotherapy

Background and PurposeCirculating tumour (ct) human papillomavirus (HPV) DNA is detectable in HPV-related oropharyngeal carcinoma (OPSCC) patients and has the potential to become an important clinical tool. This study aimed to evaluate the prognostic significance of ctHPV16-DNA kinetics during treatment with chemoradiotherapy in HPV-related OPSCC. Patients with p16-positive OPSCC recruited to the ARTSCAN III trial, comparing radiotherapy plus cisplatin with radiotherapy plus cetuximab, constituted the study cohort. Materials and methodsBlood samples before start and at the end of treatment of 136 patients were analysed. ctHPV16-DNA was quantified by real-time (q)PCR. The correlation between ctHPV16-DNA levels and tumour burden was investigated with Pearson regression analysis. The prognostic value of ctHPV16-DNA levels at baseline and decline during treatment was evaluated by area-under-the-curve (AUC) calculations and analysed with univariable and multivariable Cox proportional hazards models. ResultsctHPV16-DNA was detectable with qPCR in 108/136 patients before start of treatment and cleared in 74% of these patients at the end of treatment. Disease burden was significantly correlated with baseline ctHPV16-DNA levels (R = 0.39, p=<0.001). Both lower baseline levels and AUC-ctHPV16DNA were associated with improved progression-free survival (p = 0.01 and p < 0.001), overall survival (p = 0.013 and p = 0.002), but not local tumour control (p = 0.12 and p = 0.2, respectively), with a stronger association for AUC-ctHPV16DNA (likelihood ratio test 10.5 vs 6.5 in Cox regression analyses of progression-free survival). In multivariable analysis including tumour volume (GTV-T) and treatment allocation (cisplatin vs cetuximab), AUC-ctHPV16DNA remained a significant prognostic marker of progression-free survival. ConclusionctHPV16-DNA is an independent prognostic factor in HPV-related OPSCC.

Cellular states are coupled to genomic and viral heterogeneity in HPV-related oropharyngeal carcinoma.

Head and neck squamous cell carcinoma (HNSCC) includes a subset of cancers driven by human papillomavirus (HPV). Here we use single-cell RNA-seq to profile both HPV-positive and HPV-negative oropharyngeal tumors, uncovering a high level of cellular diversity within and between tumors. First, we detect diverse chromosomal aberrations within individual tumors, suggesting genomic instability and enabling the identification of malignant cells even at pathologically negative margins. Second, we uncover diversity with respect to HNSCC subtypes and other cellular states such as the cell cycle, senescence and epithelial-mesenchymal transitions. Third, we find heterogeneity in viral gene expression within HPV-positive tumors. HPV expression is lost or repressed in a subset of cells, which are associated with a decrease in HPV-associated cell cycle phenotypes, decreased response to treatment, increased invasion and poor prognosis. These findings suggest that HPV expression diversity must be considered during diagnosis and treatment of HPV-positive tumors, with important prognostic ramifications.

The Interplay between Age and Viral Status in EBV-Related Nasopharyngeal and HPV-Related Oropharyngeal Carcinoma Patients.

The aim of this work was to analyze the interplay between age and viral status on the outcomes in loco-regionally advanced oropharyngeal and nasopharyngeal cancer patients treated with radiotherapy and different chemotherapy combinations. A retrospective (2006-2017) analysis was performed on non-metastatic loco-regionally advanced oropharyngeal (both HPV+ and HPV-) and EBV+ nasopharyngeal cancer patients (young: &lt;65 years vs. elderly: ≥65 years) treated with radiotherapy with or without chemotherapy. The impact of age and viral status on overall (OS) and disease-free survival (DFS) were studied with multivariable models, which were adjusted for smoking, stage, comorbidities, chemotherapy dose intensity and treatment strategy. We analyzed 324 patients (146 HPV+ oropharynx, 63 HPV-, 115 nasopharynx). Elderly patients had more comorbidities, and received less intensive treatments when compared to younger subjects. Although OS and DFS were shorter in older patients, after adjustment for stage, smoking, comorbidities, treatment strategy and dose intensity, no significant differences in terms of survival were observed according to age (65 vs. 50 years of age: HR 1.89, 95% CI 0.45-7.84 for HPV+ OPC; HR 0.91, 95% CI 0.29-2.89 for HPV- OPC; HR 1.99, 95% CI 0.9-4.39 for NPC; p = 0.395). Several potential age-related (comorbidities, treatment intensity) and disease-related (stage) confounding factors play a prognostic role with differential impacts on both virus and non-virus-related tumors. In HPV+ oropharyngeal cancer and in EBV+ nasopharyngeal cancer patients, age should be considered as the expression of an array of host- and tumor-related features rather than an independent prognostic factor.

Reduced-dose radiation in human papillomavirus-associated oropharyngeal carcinoma can improve outcome: a systematic review and meta-analysis.

Despite its effectiveness, the standard course of chemoradiation for the treatment of human papillomavirus (HPV)-related oropharyngeal carcinoma (OPC) results in considerable treatment-related adverse effects. Studies proved that HPV-positive OPC is very sensitive to radiotherapy. Using de-escalation therapy as a new strategy is critical to maintaining positive outcomes while alleviating side effects. However, some studies hold that reduced dose causes insufficient effect on tumor killing. We conducted this systematic review and meta-analysis of survival and adverse reactions in patients with HPV-related OPC by retrospective analysis and evaluated the therapeutic effect of reducing the radiation dose. Data were double-selected and extracted by searching seven electronic databases, Original studies in all language treated HPV-associated OPC with reduced-dose and standard-dose therapies were included. Overall survival (OS), progression-free survival (PFS), and incidence rates of adverse events were obtained by pooling analyses. Statistical analyses were performed using RStudio Version 1.1.383 (RStudio, Boston, MA, USA) via the Meta-Analysis R Package (metafor). Heterogeneity was evaluated using the I2 statistic and the Cochran Q test. We used Stata (version 15.0) for forest graph. Thirteen studies were included in this meta-analysis, involving a dose range of 66-70 Gy for the standard treatment regimen and <66 Gy for the reduced-dose group. There was no significant difference in the age of the patients in the standard and the reduced treatment groups (60.9±5.9 vs. 58.6±2.4 years). Nine studies were included as standard cohort and thirteen studies were enrolled as reduced-dose cohort. The 2- and 3-year overall survival rates in the reduced-dose group (95.66% and 91.51%, respectively) were superior to those in the standard-dose group (88.36% and 87.46%, respectively). There was no significant difference in PFS between the two groups. A systematic review of articles on dose reduction and the standard dose was also conducted. The most common complication in reduced-dose radiation was oral mucositis (36.4%), followed by decreased white blood cell (WBC) count (30.5%) and dry mouth (29.1%). Reducing the radiation dose in patients with HPV-related OPC substantially alleviates the treatment toxicities and optimizes the quality of life of patients while at the same time maintaining favorable oncologic outcomes.

Tumor Volume Predicts for Baseline Hypoxia Status in HPV Related Oropharyngeal Carcinomas (OPC) that Underwent Major Radiation De-escalation: The 30 Reduction in Oropharyngeal Cancer Trial

<h3>Purpose/Objective(s)</h3> The 30 ROC Trial utilizes functional imaging, specifically pre-treatment (Tx) and intra-Tx fluorine-18-labeled fluoromisonidazole positron emission tomography (18F-FMISO PET) to select appropriate human papillomavirus positive (HPV+) OPC patients for major de-escalation to 30 Gy. In this trial, patients also underwent pre-Tx and weekly multiparametric magnetic resonance imaging (MRI) scans to correlate with hypoxia status. The aim of the present study was to assess the value of MRI tumor volume to predict baseline hypoxia status in HPV+OPC patients who underwent major dose de-escalation. <h3>Materials/Methods</h3> A total (N = 158) patients with cT0-2,N1-2b (AJCC 7^th ed.) p16+ OPC were enrolled. All patients had pre-Tx 18F-FMISO PET scans to assess baseline hypoxia status, and only those with baseline hypoxia underwent a repeat intra-Tx scan. Pre-Tx and weekly intra-Tx MRI scans were acquired on technology company's 3T MRI scanner using a neurovascular phased array coil. Radiation oncologists delineated gross nodal disease as regions of interest on T₂w images. Tumor volume (cm³) was calculated in ITK SNAP for each patient using the segmentation software. All standard statistical analyses were performed on RStudio 2021.09.2. <h3>Results</h3> Of the 158 patients, N=95 patients had analyzable pre-Tx and weekly on-Tx MRI scans. Based on pre-Tx 18F-FMISO PET results, increased tumor volume was associated with baseline nodal hypoxia (N=69, median 18.55 cm³, range: 3.15- 60.62) compared to initially non-hypoxic tumors (N= 26, median 6.44 cm³, range: 0.48 – 47.74, p<0.001). After the intra-Tx 18F-FMISO PET result, patients were further stratified into converted negative (N= 57), persistently hypoxic (N=12), and never hypoxic (N=26). We found that the median pre-Tx nodal volume for the persistently hypoxic (median 17.75 cm³, range 5.54- 42.93, p=0.006) and converted negative (median 18.55 cm³, range 3.15 – 60.62, p<0.001) groups was significantly (P= <0.05) increased compared to the initially hypoxia negative patients (6.44 cm³, range 0.48 – 47.74). We performed further assessment of this pattern with intra-Tx MRIs (weeks 1-4) and found that this correlation of groups with baseline hypoxia (converted negative and persistently hypoxic) continued to exhibit larger nodal volume compared to the never hypoxic group. <h3>Conclusion</h3> Pre-Tx nodal volume on MRI correlates with pre-Tx hypoxia status where the larger the volume, the higher the likelihood of hypoxia. This correlation continued throughout radiation Tx as evidenced by the weekly MRI scans.

Which future for de-intensified treatments in HPV-related oropharyngeal carcinoma?

The development of deintensified therapies aiming at reducing the treatment-related toxicity while not impairing the outcome is an unmet need in HPV+ oropharyngeal carcinoma patients. Several deintensification approaches have been explored in this setting, including induction chemotherapy with reduced chemoradiation dose in responding pts. The findings of the studies conducted so far show that the available deescalated therapy should be based on the disease risk profile. At present, we still lack robust high level data to infer that the cited interventions are equivalent or superior to standard of care treatments. However, literature data suggest that approximately 70% of low-risk patients might receive a deintensified approach by including either surgery or induction chemotherapy. In the context of high-risk disease, more than 80% of patients may undergo a deintensified loco-regional treatment by neoadjuvant systemic therapy. Epidemiological data suggest that in the next decades, most of the HPV-related OPSCC patients will be made of old and possibly frail individuals. However, this patient population was excluded from most of the studies conducted so far. Therefore, there is a strong need for clinical trials to define risk-based deescalation strategies in this population and in younger patients as well.

Investigation of the diversity of human papillomavirus 16 variants and L1 antigenic regions relevant for the prevention of human papillomavirus-related oropharyngeal cancer in Japan

ObjectiveThis study aimed to investigate the distribution of human papillomavirus 16 (HPV16) variants that contribute to the development of HPV-related oropharyngeal carcinoma (HPV-OPC) in the Japanese population and to evaluate genetic variations in the sequence encoding the L1 antigen region of the viral outer shell that is targeted by existing vaccines and is relevant for designing a prevention strategy to combat the exponential increase in HPV-OPC cases in Japan. MethodsSeventy Japanese HPV-OPC patients treated at Tohoku University Hospital were included in the study. DNA was extracted from formalin-fixed, paraffin-embedded tissue samples. Polymerase chain reaction and direct nucleotide sequencing were performed to determine the nucleotide polymorphisms necessary for the classification of HPV16 variants and to assess genetic diversity in the HPV16 L1 antigen region, including the BC, DE, EF, FG, and HI loops. ResultsThe most common variant of HPV16 was the A4 sublineage (88.6%), conventionally called the Asian type, followed by the A1/2/3 (10.0%) sublineage, classified as the European type. The only nonsynonymous substitution detected in the L1 antigen loop region was p.N181T in the EF loop, which was found in 28/70 (40%) cases. In contrast, no nonsynonymous substitutions were observed in the DE, FG, and HI loops, which are particularly important regions in the antigen loop targeted by existing HPV vaccines. ConclusionThe most common HPV16 variant in Japanese HPV-OPC patients was the A4 subtype. The L1 antigen region is highly conserved, suggesting sufficient efficacy of existing HPV vaccines. These findings provide important information that will aid in the design of an HPV16 infection control strategy using existing HPV vaccines to prevent the spread of HPV-OPC in Japan.

Mixed HPV-related Neuroendocrine Carcinoma and HPV-related Squamous Cell Carcinoma of the Base of Tongue in a Patient With Incidental Identification of Synchronous Metastatic Papillary Thyroid Carcinoma

While it is not uncommon in patients with head and neck cancer to present with multiple metachronous primary neoplasms, rarely do these present as a singular mass composed of intertwined, histologically distinct malignant tumors. Sometimes referred to as collision tumors, these entities are poorly understood and only appear in a handful of case studies in the literature. Here we present a 58-year-old male diagnosed with a human papillomavirus-related collision tumor consisting of oropharyngeal squamous cell carcinoma and small-cell neuroendocrine carcinoma, as well as an incidentally discovered metastatic thyroid papillary carcinoma, despite an unremarkable thyroid gland. The patient underwent transoral robotic base-of-tongue resection and partial pharyngectomy with selective neck dissection followed by chemoradiotherapy. At the 18-month follow-up the patient was doing well. His thyroid was normal and no recurrent or metastatic carcinoma was identified on the computed tomography and positron-emission tomography/computed tomography imaging findings. To the best of our knowledge, this is the first such case in English literature. This case demonstrates the importance of tumor morphology and immunohistochemical testing in HPV-related oropharyngeal carcinomas, despite the overall good prognosis of such tumors, due to the possibility of synchronous or colliding primary neoplasms.

De-Escalation Strategies of (Chemo)Radiation for Head-and-Neck Squamous Cell Cancers-HPV and Beyond.

Simple SummaryHPV-related oropharyngeal squamous cell carcinoma patients have a very good prognosis but are often suffering from long-term treatment-induced toxicities. Therefore, a plethora of de-escalation trials is examining whether treatment for HPV-induced oropharyngeal carcinoma can be de-escalated without compromising the favorable outcomes. The purpose of this review was to present and critically discuss the published as well as the ongoing de-escalation trials in head-and-neck squamous cell carcinoma, in particular for HPV-related oropharyngeal carcinoma. De-escalation studies are using several approaches such as radiotherapy dose reduction, target volume reduction, omission of concomitant chemotherapy, replacement of cisplatin through less toxic systemic agents, omission of adjuvant (chemo)radiation after primary surgery and selection of suitable patients by induction chemotherapy or peritherapeutic hypoxia imaging. Although many promising results have been obtained from several Phase I and II trials, the two Phase III de-escalation trials failed to show the equivalence of the de-escalated treatment arm, so that so far, no treatment de-escalation can be recommended outside of clinical trials.Oncological outcomes for head-and-neck squamous cell carcinoma (HNSCC) patients are still unsatisfactory, especially for advanced tumor stages. Besides the moderate survival rates, the prevalence of severe treatment-induced normal tissue toxicities is high after multimodal cancer treatments, both causing significant morbidity and decreasing quality of life of surviving patients. Therefore, risk-adapted and individualized treatment approaches are urgently needed for HNSCC patients to optimize the therapeutic gain. It has been a well-known fact that especially HPV-positive oropharyngeal squamous cell carcinoma (OSCC) patients exhibit an excellent prognosis and may therefore be subject to overtreatment, resulting in long-term treatment-related toxicities. Regarding the superior prognosis of HPV-positive OSCC patients, treatment de-escalation strategies are currently investigated in several clinical trials, and HPV-positive OSCC may potentially serve as a model for treatment de-escalation also for other types of HNSCC. We performed a literature search for both published and ongoing clinical trials and critically discussed the presented concepts and results. Radiotherapy dose or volume reduction, omission or modification of concomitant chemotherapy, and usage of induction chemotherapy are common treatment de-escalation strategies that are pursued in clinical trials for biologically selected subgroups of HNSCC patients. While promising data have been reported from various Phase II trials, evidence from Phase III de-escalation trials is either lacking or has failed to demonstrate comparable outcomes for de-escalated treatments. Therefore, further data and a refinement of biological HNSCC stratification are required before deescalated radiation treatments can be recommended outside of clinical trials.

Cranium metastasis of HPV positive oropharyngeal squamous cell carcinoma

Head and neck squamous cell carcinomas rarely cause cranial metastases, but HPV related subgroup is known for unusual metastasis sites on the body. Despite the good overall treatment responses in this group, intracranial metastases are always accepted as a sign of rapid deterioration. We present a case of cranium metastasis of HPV related oropharyngeal squamous cell carcinoma, which had been very well responded to the treatment for years but deteriorates in a short period after the cranium metastasis.

Impact of Smoking on Survival Outcomes in HPV-Related Oropharyngeal Carcinoma: A Meta-analysis.

Characterize the survival impact of smoking on HPV-related (human papillomavirus) oropharyngeal squamous cell carcinoma. Articles from 2000 to 2019 in the PubMed, Embase, and Cochrane Library databases were systematically reviewed for content and inclusion/exclusion criteria. Two reviewers independently analyzed the databases for eligibility and quality of the articles. Demographic data, smoking history, and survival outcomes were recorded. Hazard ratios and 95% CIs were collectively analyzed through a random effects meta-analysis model. Fifteen articles were included in the meta-analysis for overall survival, disease-specific survival, disease-free survival, progression-free survival, and locoregional recurrence outcomes. The overall survival hazard ratio was 2.4 for ever having smoked (95% CI, 1.4-4.0; P = .0006, I2 = .384) and 3.2 for current smoking (95% CI, 2.2-4.6; P < .0001, I2 = 0). The hazard ratio for disease-specific survival in current smokers was 6.3 (95% CI, 1.3-29.3; P = .0194, I2 = 0). Ever smoking had a larger impact on overall survival and disease-specific survival than the 10-pack year smoking threshold. Smoking negatively affects survival in patients with HPV-related oropharyngeal carcinoma across all outcomes. Current smoking during treatment is associated with the greatest reduction in survival, possibly secondary to diminished radiation therapy efficacy.

Distinguishing between HPV-Associated Metastatic Anal Squamous Cell Cancer and HPV-Associated Oropharyngeal Cancer

The histology and immunohistochemistry (IHC) of primary and metastatic diseases from a human papilloma virus- (HPV-) related anal squamous carcinoma (ASCC) would typically demonstrate the same histology as an HPV-related oropharyngeal squamous carcinoma (OPSCC). However, determining whether a site of squamous cell carcinoma represents distant metastatic ASCC versus a metastatic HPV-related metastasis from an OPSCC to a regional lymph node carries profound prognostic and therapeutic implications. A patient with a history of locally advanced ASCC treated with standard concurrent radiation therapy and chemotherapy in 2015 is described. In 2018, an enlarged supraclavicular lymph node was excised demonstrating squamous cell carcinoma and radiographic staging revealed no other areas suspicious for malignancy. Direct laryngoscopy with operating telescope and biopsies demonstrated squamous cell carcinoma at the tongue base. Described here are assays that might be considered in distinguishing between whether a focus distant from a previously identified ASCC represents metastatic disease or instead a separate primary HPV-related cancer.

Demographic and Socioeconomic Factors Associated With Metastases at Presentation in HPV-Related Squamous Cell Carcinoma of the Head and Neck: An NCDB Analysis.

Human papillomavirus (HPV)-related squamous cell carcinomas of the head and neck (SCCHNs) tend to have a distinct prognosis. Socioeconomic and demographic factors associated with metastatic disease at presentation and diagnosis in patients with HPV-related SCCHN tumors were examined. The National Cancer Database (NCDB) was queried to assess patients with HPV-related oropharyngeal carcinomas (HPVOPCAs) and HPV-related nonoropharyngeal carcinomas (HPVNOPCAs) diagnosed between 2010 and 2014. Rate of metastases at presentation was analyzed using clinical M stage. Multivariable analysis was performed evaluating race, ethnicity, sex, age, facility location, facility type, insurance status, income, education, and tumor and nodal stage using logistic regression. A total of 12,857 patients with HPVOPCA and 952 patients with HPVNOPCA were included. Private insurance was carried by 64% and 47% of patients with HPVOPCA and HPVNOPCA, respectively. HPVOPCA was located in the tonsil in 56% of patients. For both HPVOPCA and HPVNOPCA, there was no meaningful difference in distant metastasis at presentation based on facility type or location, sex, race, Hispanic ethnicity, or urban or rural location. For HPVOPCA, there were significantly lower odds of metastasis in privately insured patients compared with uninsured patients (odds ratio [OR], 0.37; 95% CI, 0.21 to 0.64; P < .001) and higher odds of metastasis for patients living in census tracts with the lowest rates of high school graduates compared with the highest rates (OR, 1.81; 95% CI, 1.02 to 3.19; P = .041) and for patients with higher tumor stage (OR, 3.67, 95% CI, 2.25 to 5.99; P < .001) and nodal stage (OR, 3.34; 95% CI, 2.11 to 5.29; P < .001). For HPVNOPCA, neither higher T or N stage nor any demographic features were found to be associated with metastasis at presentation. This large retrospective analysis identifies likely modifiable risk factors for metastatic presentation in HPVOPCA. Educational interventions may result in modifications of these patterns.

HPV-related oropharyngeal carcinoma remains infrequent over 25 years in a Brazilian Oral Pathology Center: A cross-sectional study with literature review.

The aim was to evaluate the frequency, clinicopathological features, and HPV status of oropharyngeal squamous cell carcinoma (OP-SCC) and benign HPV-related epithelial lesions of the oropharynx over the last 25 years. Moreover, a literature review was performed to investigate HPV frequency in OP-SCC samples diagnosed in Brazilian Centers. A cross-sectional study analyzed OP-SCC, squamous papilloma, verruca vulgaris, and condyloma accuminatum, diagnosed from 1997 to 2021. HPV status of OP-SCC was determined by immunohistochemistry and "in situ" hybridization. Bivariate statistics were performed (p≤0.05). For the literature review, MEDLINE/PubMed, Web of Science, EMBASE, and Scopus were searched. Two independent reviewers assessed the studies for eligibility. Cross-sectional: 211 OP-SCC (63.0%) and 124 benign lesions (37.0%) were included. OP-SCC frequency increased gradually over time, whereas benign lesions had steady trends. OP-SCC affected more males (n= 171; 81.0%), though the relative frequency in females rose over time. Smoking (n= 127; 60.2%) was common in OP-SCC. Nineteen OP-SCC (13.0%) were positive for HPV. HPV-positive and HPV-negative tumors had similar clinicopathological features (p>0.05). Benign lesions predominated in middle-aged (n= 32; 26.7%) women (n= 71; 57.3%), in the soft palate (n=101; 81.5%). 32 studies were included, and in 60% of them, HPV frequency in OP-SCC was less than 25%. OP-SCC prevalence has been increasing, and it was mostly associated with smoking and alcohol rather than with HPV infection in Brazil. Benign lesions had a stationary frequency over the evaluated period.

Roles of APOBEC in carcinogenesis and clinical feature of HPV-related oropharyngeal carcinoma

Roles of APOBEC in carcinogenesis and clinical feature of HPV-related oropharyngeal carcinoma

Current Perspective on HPV-Associated Oropharyngeal Carcinomas and the Role of p16 as a Surrogate Marker of High-Risk HPV

The incidence of oropharyngeal carcinomas associated with human papillomavirus (HPV) is continuously increasing. HPV-positive and -negative oropharyngeal carcinomas have different epidemiological, clinical, and molecular features, with HPV-positive tumors having a better response to treatment and better prognosis. An adequate staging system for HPV-related oropharyngeal carcinomas is needed, as the American Joint Committee on Cancer 7th Edition did not consider their unique biological behavior. At present, oropharyngeal carcinomas are subdivided into p16 positive and p16 negative tumors, based on their expression of p16, a surrogate marker of high-risk HPV. This review summarizes current knowledge of HPV-associated oropharyngeal carcinomas with emphasis on their molecular features and histopathology, as well as summarizes and compares HPV detection methods and genotyping techniques. This review also describes the prognostic significance of p16 expression in these tumors and significant changes in the staging of oropharyngeal carcinomas based on p16 expression, together with the justifications for these changes. Finally, this review reports the recommendations of the College of American Pathologists for testing HPV in head and neck cancers, supported by the American Society of Clinical Oncology. This work was supported by the Ministry of Health of the Czech Republic, grant No. 15-31627A. All rights reserved. Auto&#345;i deklarují, &#382;e v souvislosti s p&#345;edm&#283;tem studie nemají &#382;ádné komer&#269;ní zájmy. Redak&#269;ní rada potvrzuje, &#382;e rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských &#269;asopis&#367;. Submitted: 18. 2. 2019 Accepted: 30. 5. 2019.

De-escalation Protocols in HPV-related Oropharyngeal Carcinoma in Chinese Populations

De-escalation Protocols in HPV-related Oropharyngeal Carcinoma in Chinese Populations

Factors associated with metastatic presentation in HPV-related squamous cell carcinoma of the head and neck (SCCHN): A National Cancer Database (NCDB) analysis.

e18213 Background: Metastasis is an ominous sign in SCCHN. Human papillomavirus (HPV) infection-associated SCCHN cancers tend to have a distinct prognosis. Factors that are associated with metastatic disease at the time of presentation and diagnosis in patients with HPV-related SCCHN tumors were examined. Methods: NCDB was queried to assess 12,857 patients with HPV-related oropharyngeal carcinomas (HPVOPCA) and 952 patients with HPV related non-oropharyngeal carcinomas (HPVNOPCA) diagnosed between between 2010-2014 with non-missing survival or M stage. Rate of metastases at presentation was analyzed using clinical M stage. Multivariable analysis was performed evaluating race, ethnicity, sex, age, facility location, facility type, insurance status, income, education, urban/rural location, surgery, radiation, and chemotherapy using logistic regression. Results: In both HPVOPCA and HPVNOPCA, over 90% of patients were white. Private insurance was carried by 64% and 47% of patients with HPVOPCA and HPVNOPCA, respectively. HPVOPCA cancer was located in the tonsil in 47% of cases. Patients with HPVOPCA were more likely to present with advanced nodal disease than patients with HPVNOPCA. For both HPVOPCA and HPVNOPCA, there was no meaningful difference in the rate of distant metastasis at presentation in facility type or location, sex, race, Hispanic ethnicity, or urban rural location. For HPVOPCA, there were significantly lower odds of metastasis in privately insured patients vs. uninsured patients (HR: 0.35, 95% CI: 0.21-0.59, p &lt; 0.001), and higher odds of metastasis for those living in census tracts with the lowest rates of high school graduates vs. those living in census tracts with the highest rates of high school graduates (HR: 1.82, 95% CI: 1.07-3.09, p = 0.026). For HPVNOPCA, patients living in census tracts with the lowest rates of high school graduates were less likely to develop metastasis compared to those living in census tracts with the highest rates of high school graduates (p = 0.031). Conclusions: This large retrospective analysis identifies likely modifiable risk factors for metastatic presentation in HPV-related SCCHN. Health policies and educational interventions may result in modifications of these patterns.

Impact of AJCC 8th Edition Clinical T- and N-Classifications on Oncologic Outcomes and Patterns of Failure in HPV-Related Oropharyngeal Carcinoma

Impact of AJCC 8th Edition Clinical T- and N-Classifications on Oncologic Outcomes and Patterns of Failure in HPV-Related Oropharyngeal Carcinoma

The Association of Canonical Speech- and Swallow-Related Dosimetric Constraints with Patient-Reported Quality of Life Outcomes: Results from a Phase II Trial of Dose De-Escalated Chemoradiation for HPV-Associated, Locally-Advanced Oropharyngeal Carcinoma

Radiation dose de-escalation for patients with human papillomavirus (HPV)-related oropharyngeal carcinoma may improve quality of life. We conducted an exploratory exercise to examine potential relationships between canonical dosimetric parameters and speech- and swallow-related and overall patient-reported quality of life outcomes on a subset of patients treated on a phase II trial of de-escalated chemoradiation for HPV-related oropharyngeal carcinoma. An analysis was performed of 24 patients treated at a single-institution on a phase II, prospective study of induction chemotherapy followed by dose de-escalated chemoradiation for HPV-related, locally-advanced oropharyngeal carcinoma. Following two cycles of induction carboplatin/paclitaxel, reduced-dose chemoradiation with concurrent paclitaxel was administered to 54-60 Gy in 27-30 fractions. Intensity-modulated radiotherapy was used for all patients. Univariable logistic regression analysis was used to evaluate potential associations between multiple speech-and swallow-related dosimetric constraints and quality of life domains at 3 and 12 months post-treatment involving swallowing, chewing, speech, taste, and saliva, as well as overall quality of life, using the University of Washington Quality of Life instrument. Canonical models were constructed to analyze dosimetry to the temporomandibular joints, oral cavity, lips, parotid glands, submandibular glands, larynx, pharynx, cricopharyngeal inlet, and cervical esophagus, as analyzed by maximum, mean, and/or partial-volume parameters. The post-chemotherapy gross tumor volume, planning target volume (PTV) receiving the high, intermediate, and low dose levels, and combined volume of all PTV dose levels were also analyzed. Twenty-five percent of patients had T3-T4 tumors, and 13% had N2c nodal disease. Thirteen percent had >10 pack-year smoking history. At 12 months, a decreased taste domain score was significantly associated with a higher volume of high-dose level PTV (p=0.028). Also, a decreased health-related quality of life score at 12 months was significantly associated with a higher contralateral parotid gland mean dose (p=0.037), higher contralateral parotid gland V30Gy (p=0.046), and higher cricopharyngeal inlet mean dose (p=0.036). No dosimetric parameters were significantly associated with quality of life differences at 3 months (p>0.05, for all). For patients treated by de-escalated chemoradiation, canonical dosimetric constraints for conventional chemoradiation are poorly correlated with speech- and swallow-related and overall quality of life outcomes. While a smaller high-dose PTV, lower contralateral parotid gland dose, and lower cricopharyngeal inlet dose appear to be related to better quality of life outcomes, these require additional validation. Future studies of de-escalated chemoradiation may reveal new dosimetric constraints to help guide treatment planning.