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Viruses Jan 2023The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased in the past decades due to carcinogenic HPV infection. As this patient group suffers from...
The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased in the past decades due to carcinogenic HPV infection. As this patient group suffers from considerable mortality and treatment morbidity it is important to improve prognostic strategies in OPSCC. Inflammation plays a key role in cancer and the neutrophil-to-lymphocyte ratio (NLR) in blood has been suggested as a prognostic factor for OPSCC. This study aimed to investigate the prognostic impact of NLR on overall survival (OS) and recurrence-free survival (RFS) in a retrospective cohort of 1370 patients. Included patients had pretreatment neutrophil and lymphocyte counts available, as well as a known HPV status. Patients were treated with curative intent according to Danish national guidelines. We stratified patients in groups by NLR < 2, NLR 2−4, or NLR > 4 and analyzed the influence of the NLR tertile on OS and RFS. Kaplan−Meier curves illustrated survival probability in OS and RFS in the general cohort and were stratified by HPV status. We found that an increasing NLR was associated with inferior OS (HR = 1.5 for NLR > 4) and RFS (HR = 1.6 for NLR 2−4; HR = 1.8 for NLR > 4) in multivariable analysis. The Kaplan−Meier curves displayed inferior OS and RFS with an increasing NLR for both HPV+ and HPV− patients. In conclusion, we showed that an increasing NLR is prognostic for a worse outcome of OPSCC independently of HPV status. There are possible uses of NLR in prognostication and treatment de-escalation although further studies are warranted to determine the clinical utility.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Prognosis; Retrospective Studies; Neutrophils; Papillomavirus Infections; Oropharyngeal Neoplasms; Carcinoma, Squamous Cell; Lymphocytes; Head and Neck Neoplasms
PubMed: 36680237
DOI: 10.3390/v15010198 -
Journal of Experimental & Clinical... Sep 2022Immune checkpoint inhibitors (ICI) are approved for treatment of recurrent or metastatic oropharyngeal head and neck squamous cell carcinoma in the first- and...
The immune microenvironment of HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma: a multiparametric quantitative and spatial analysis unveils a rationale to target treatment-naïve tumors with immune checkpoint inhibitors.
BACKGROUND
Immune checkpoint inhibitors (ICI) are approved for treatment of recurrent or metastatic oropharyngeal head and neck squamous cell carcinoma in the first- and second-line settings. However, only 15-20% of patients benefit from this treatment, a feature increasingly ascribed to the peculiar characteristics of the tumor immune microenvironment (TIME).
METHODS
Immune-related gene expression profiling (GEP) and multiplex immunofluorescence (mIF) including spatial proximity analysis, were used to characterize the TIME of 39 treatment-naïve oropharyngeal squamous cell carcinomas (OPSCC) and the corresponding lymph node metastases. GEP and mIF results were correlated with disease-free survival (DFS). HPV-positive tumors disclosed a stronger activation of several immune signalling pathways, as well as a higher expression of genes related to total tumor-infiltrating lymphocytes, CD8 T cells, cytotoxic cells and exhausted CD8 cells, than HPV-negative patients. Accordingly, mIF revealed that HPV-positive lesions were heavily infiltrated as compared to HPV-negative counterparts, with a higher density of T cells and checkpoint molecules. CD8+ T cells appeared in closer proximity to tumor cells, CD163+ macrophages and FoxP3+ cells in HPV-positive primary tumors, and related metastases. In HPV-positive lesions, PD-L1 expression was increased as compared to HPV-negative samples, and PD-L1+ tumor cells and macrophages were closer to PD-1+ cytotoxic T lymphocytes. Considering the whole cohort, a positive correlation was observed between DFS and higher levels of activating immune signatures and T cell responses, higher density of PD-1+ T cells and their closer proximity to tumor cells or PD-L1+ macrophages. HPV-positive patients with higher infiltration of T cells and macrophages had a longer DFS, while CD163+ macrophages had a negative role in prognosis of HPV-negative patients.
CONCLUSIONS
Our results suggest that checkpoint expression may reflect an ongoing antitumor immune response. Thus, these observations provide the rationale for the incorporation of ICI in the loco-regional therapy strategies for patients with heavily infiltrated treatment-naïve OPSCC, and for the combination of ICI with tumor-specific T cell response inducers or TAM modulators for the "cold" OPSCC counterparts.
Topics: B7-H1 Antigen; Carcinoma, Squamous Cell; Forkhead Transcription Factors; Head and Neck Neoplasms; Humans; Immune Checkpoint Inhibitors; Oropharyngeal Neoplasms; Papillomavirus Infections; Programmed Cell Death 1 Receptor; Spatial Analysis; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment
PubMed: 36123711
DOI: 10.1186/s13046-022-02481-4 -
Wiener Klinische Wochenschrift Nov 2021The aim was to assess the prognostic value of the newly proposed prognostic index (PI) in patients with p16-positive oropharyngeal squamous cell carcinoma.
BACKGROUND
The aim was to assess the prognostic value of the newly proposed prognostic index (PI) in patients with p16-positive oropharyngeal squamous cell carcinoma.
METHODS
Patients treated with primary surgery from 2012 to 2019 with available preoperative (0-2 days) values of C‑reactive protein and white blood cell counts needed for calculation of the PI, were included. Main outcome measures were overall survival (OS) and disease-free survival (DFS). The PI was dichotomized into low (PI = 0) and high (PI ≥ 1).
RESULTS
In this study 36 patients were included. Average overall (OS) and disease-free survival (DFS) were 3.3 years (range 0.2-12.3 years) and 2.8 years (0.0-9.8 years), respectively. The overall mortality was 16.7% (n = 6) and a recurrent disease was observed in 30.6% of patients (n = 11). Low PI was associated with better overall survival (mean OS 10.1 ± 1.4 years, 95% confidence interval, CI 7.3-12.9 years vs. 1.9 ± 0.4, 95% CI 1.3-2.6 years, p < 0.01; mean DFS 8.5 ± 0.7 years, 95% CI 7.1-9.6 years vs. 1.0 ± 0.3 years, 95% CI 0.5-1.5 years, p < 0.01).
CONCLUSION
The PI might be an easily obtainable outcome prognosticator in p16-positive oropharyngeal squamous cell carcinoma patients. Analyzing routinely obtained blood samples can contribute to identifying high-risk patients.
Topics: Disease-Free Survival; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Prognosis; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck
PubMed: 34143263
DOI: 10.1007/s00508-021-01885-0 -
ORL; Journal For Oto-rhino-laryngology... 2023The aim of this study was to investigate the impact of primary transoral robotic surgery (TORS) versus radiotherapy (RT) on progression-free survival (PFS), overall...
INTRODUCTION
The aim of this study was to investigate the impact of primary transoral robotic surgery (TORS) versus radiotherapy (RT) on progression-free survival (PFS), overall survival (OS), and 1-year swallowing function for patients with early-stage HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).
METHODS
Patients with stage I-II (AJCC 8th Ed.) HPV-associated OPSCC treated with TORS followed by risk-adapted adjuvant therapy or (chemo)radiotherapy between 2014 and 2019 were identified. PFS, OS, and swallowing outcomes including gastrostomy tube (GT) use/dependence, and Functional Oral Intake Scale (FOIS) change over 1 year were compared.
RESULTS
One hundred sixty-seven patients were analyzed: 116 treated with TORS with or without adjuvant RT and 51 treated with RT (50 chemoRT). The RT group had more advanced tumor/nodal stage, higher comorbidity, and higher rates of concurrent chemotherapy. There were no differences in 3-year PFS (88% TORS vs. 75% RT) or OS (90% vs. 81%) between groups, which persisted after adjusting for stage, age, and comorbidity. GT use/dependence rates were higher in the RT group. Mean (SD) FOIS scores in the TORS group were 6.9 (0.4) at baseline and 6.4 (1.0) at 1 year, compared with 6.7 (0.6) and 5.6 (1.7) for the RT group. Only clinical nodal stage was found to be significantly associated with FOIS change from baseline to 1 year.
CONCLUSION
There were no differences in PFS or OS between patients treated with primary TORS or RT for early-stage HPV-associated OPSCC. Clinical N2 status is associated with FOIS change at 1 year and may be the major factor affecting long-term swallowing function, irrespective of primary treatment modality.
Topics: Humans; Deglutition; Head and Neck Neoplasms; Human Papillomavirus Viruses; Oropharyngeal Neoplasms; Papillomavirus Infections; Robotic Surgical Procedures; Squamous Cell Carcinoma of Head and Neck; Postoperative Complications
PubMed: 37647863
DOI: 10.1159/000531995 -
European Journal of Cancer (Oxford,... May 2024Uncertainty persists regarding clinical and treatment variations crucial to consider when comparing high human papillomavirus (HPV)-prevalence oropharyngeal squamous...
BACKGROUND
Uncertainty persists regarding clinical and treatment variations crucial to consider when comparing high human papillomavirus (HPV)-prevalence oropharyngeal squamous cell carcinoma (OPSCC) cohorts for accurate patient stratification and replicability of clinical trials across different geographical areas.
METHODS
OPSCC patients were included from The University of Texas MD Anderson Cancer Center (UTMDACC), USA and from The University Hospital of Copenhagen, Denmark from 2015-2020, (n = 2484). Outcomes were 3-year overall survival (OS) and recurrence-free interval (RFI). Subgroup analyses were made for low-risk OPSCC patients (T1-2N0M0) and high-risk patients (UICC8 III-IV).
RESULTS
There were significantly more HPV-positive (88.2 % vs. 63.1 %), males (89.4 % vs. 74.1 %), never-smokers (52.1 % vs. 23.7 %), lower UICC8-stage (I/II: 79.3 % vs. 68 %), and fewer patients treated with radiotherapy (RT) alone (14.8 % vs. 30.3 %) in the UTMDACC cohort. No difference in the adjusted OS was observed (hazard ratio [HR] 1.21, p = 0.23), but a significantly increased RFI HR was observed for the Copenhagen cohort (HR: 1.74, p = 0.003). Subgroup analyses of low- and high-risk patients revealed significant clinical and treatment differences. No difference in prognosis was observed for low-risk patients, but the prognosis for high-risk patients in the Copenhagen cohort was worse (OS HR 2.20, p = 0.004, RFI HR 2.80, p = 0.002).
CONCLUSIONS
We identified significant differences in clinical characteristics, treatment modalities, and prognosis between a Northern European and Northern American OPSCC population. These differences are important to consider when comparing outcomes and for patient stratification in clinical trials, as reproducibility might be challenging.
Topics: Male; Humans; Squamous Cell Carcinoma of Head and Neck; Prognosis; Carcinoma, Squamous Cell; Human Papillomavirus Viruses; Oropharyngeal Neoplasms; Papillomavirus Infections; Prevalence; Reproducibility of Results; Head and Neck Neoplasms; Denmark; Papillomaviridae
PubMed: 38452723
DOI: 10.1016/j.ejca.2024.113983 -
Radiotherapy and Oncology : Journal of... Jul 2023This study provides a review of the literature assessing whether semiquantitative PET parameters acquired at baseline and/or during definitive (chemo)radiotherapy... (Review)
Review
Prognostic and predictive values of baseline and mid-treatment FDG-PET in oropharyngeal carcinoma treated with primary definitive (chemo)radiation and impact of HPV status: Review of current literature and emerging roles.
BACKGROUND AND PURPOSE
This study provides a review of the literature assessing whether semiquantitative PET parameters acquired at baseline and/or during definitive (chemo)radiotherapy ("prePET" and "iPET") can predict survival outcomes in patients with oropharyngeal squamous cell carcinoma (OPC), and the impact of human papilloma virus (HPV) status.
MATERIAL AND METHODS
A literature search was carried out using PubMed and Embase between 2001 to 2021 in accordance with PRISMA.
RESULTS
The analysis included 22 FDG-PET/CT studies [1-22], 19 pre-PET and 3 both pre-PET and iPET, The analysis involved 2646 patients, of which 1483 are HPV-positive (17 studies: 10 mixed and 7 HPV-positive only), 589 are HPV-negative, and 574 have unknown HPV status. Eighteen studies found significant correlations of survival outcomes with pre-PET parameters, most commonly primary or "Total" (combined primary and nodal) metabolic tumour volume and/or total lesional glycolysis. Two studies could not establish significant correlations and both employed SUVmax only. Two studies also could not establish significant correlations when taking into account of the HPV-positive population only. Because of the heterogeneity and lack of standardized methodology, no conclusions on optimal cut-off values can be drawn. Ten studies specifically evaluated HPV-positive patients: five showed positive correlation of pre-PET parameters and survival outcomes, but four of these studies did not include advanced T or N staging in multivariate analysis, and two studies only showed positive correlations after excluding high risk patients with smoking history or adverse CT features. Two studies found that prePET parameters predicted treatment outcomes only in HPV-negative but not HPV-positive patients. Two studies found that iPET parameters could predict outcomes in HPV-positive patients but not prePET parameters.
CONCLUSION
The current literature supports high pre-treatment metabolic burden prior to definitive (chemo)radiotherapy can predict poor treatment outcomes for HPV-negative OPC patients. Evidence is conflicting and currently does not support correlation in HPV-positive patients.
Topics: Humans; Prognosis; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Human Papillomavirus Viruses; Carcinoma, Squamous Cell; Oropharyngeal Neoplasms; Head and Neck Neoplasms; Retrospective Studies; Radiopharmaceuticals
PubMed: 37142128
DOI: 10.1016/j.radonc.2023.109686 -
Cancer Research and Treatment Apr 2022This study aimed to compare the outcomes of primary radiotherapy (RT) versus surgery in early-stage human papilloma virus-positive oropharyngeal squamous cell carcinoma...
PURPOSE
This study aimed to compare the outcomes of primary radiotherapy (RT) versus surgery in early-stage human papilloma virus-positive oropharyngeal squamous cell carcinoma (hpv+OPC), and investigate the preoperative clinical factors that can predict the requirement for postoperative adjuvant treatment.
MATERIALS AND METHODS
This multicenter study included 166 patients with American Joint Committee on Cancer 8th edition-Stages I-II hpv+OPC. Sixty (36.1%) and 106 (63.9%) patients underwent primary (concurrent chemo)radiotherapy [(CC)RT] and surgery, respectively. Seventy-eight patients (73.6%) in the surgery group received postoperative (CC)RT.
RESULTS
With a median follow-up of 45.6 months for survivors, the 2-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) for RT/surgery were 97.8%/96.4%, 91.1%/92.0%, and 92.9%/93.3%, respectively. In multivariate analyses, patients with synchronous radiologic extranodal extension and conglomeration (ENEcong) of metastatic lymph nodes (LNs) showed significantly poorer OS (p=0.047), PFS (p=0.001), and LC (p=0.003). In patients undergoing primary surgery, two or more clinically positive LN metastases (odds ratio [OR], 5.15; p=0.004) and LN metastases with ENEcong (OR, 3.75; p=0.009) were predictors of postoperative chemoradiotherapy. No patient in the primary RT group demonstrated late severe toxicity whereas three (2.8%), one (0.9%), and one (0.9%) patient in the surgery group showed grade 3 dysphagia, grade 3 xerostomia, and fatal oral cavity bleeding.
CONCLUSION
We found no differences in OS, PFS, and LC between upfront RT and surgery in stage I-II hpv+OPC which warrants comparison through a prospective trial in the treatment de-escalation era. However, most early-stage hpv+OPC patients undergoing surgery received adjuvant (CC)RT. Pretreatment LN findings were prognostic and predictive for adjuvant treatment.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prospective Studies; Squamous Cell Carcinoma of Head and Neck
PubMed: 34176249
DOI: 10.4143/crt.2021.441 -
The British Journal of Radiology Sep 2022The clinical behaviour and outcomes of patients with oropharyngeal cancer (OPC) may be dichotomised according to their association with human papilloma virus (HPV)... (Review)
Review
The clinical behaviour and outcomes of patients with oropharyngeal cancer (OPC) may be dichotomised according to their association with human papilloma virus (HPV) infection. Patients with HPV-associated disease (HPV+OPC) have a distinct demographic profile, clinical phenotype and demonstrate considerably better responses to chemoradiotherapy. This has led to a reappraisal of staging and treatment strategies for HPV+OPC, which are underpinned by radiological data. Structural modalities, such as CT and MRI can provide accurate staging information. These can be combined with ultrasound-guided tissue sampling and functional techniques (such as diffusion-weighted MRI and F-fludeoxyglucose positron emission tomography-CT) to monitor response to treatment, derive prognostic information, and to identify individuals who might benefit from intensification or deintensification strategies. Furthermore, advanced MRI techniques, such as intravoxel incoherent motion and perfusion MRI as well as application of artificial intelligence and radiomic techniques, have shown promise in treatment response monitoring and prognostication. The following review will consider the contemporary role and knowledge on imaging in HPV+OPC.
Topics: Alphapapillomavirus; Artificial Intelligence; Head and Neck Neoplasms; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis; Squamous Cell Carcinoma of Head and Neck; Tomography, X-Ray Computed
PubMed: 35687667
DOI: 10.1259/bjr.20220149 -
JAMA Oncology Mar 2022Several de-escalation strategies for human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC) have focused on deintensifying gross disease treatment....
Evaluation of Substantial Reduction in Elective Radiotherapy Dose and Field in Patients With Human Papillomavirus-Associated Oropharyngeal Carcinoma Treated With Definitive Chemoradiotherapy.
IMPORTANCE
Several de-escalation strategies for human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC) have focused on deintensifying gross disease treatment. Reduction of radiotherapy dose and target volume to subclinical regions may achieve good clinical outcomes with favorable patient quality of life (QOL).
OBJECTIVE
To determine outcomes from a systematic approach of reducing radiotherapy dose and target volume to the elective treatment regions in patients with HPV-associated OPC undergoing concurrent chemoradiotherapy (CCRT).
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study included 276 consecutive patients with HPV-positive OPC receiving CCRT from March 1, 2017, to July 31, 2019. Data were analyzed from February 23 to September 13, 2021.
INTERVENTIONS
Elective nodal and subclinical regions received 30 Gy of radiotherapy in 15 fractions, followed by a cone down of 40 Gy in 20 fractions to gross disease for a total dose of 70 Gy. The high retropharyngeal nodal basins in the node-negative neck and bilateral levels IB and V basins were omitted.
MAIN OUTCOMES AND MEASURES
Patients were followed up to evaluate locoregional control as the primary outcome and distant metastasis-free survival, progression-free survival, and overall survival as secondary outcomes. Quality-of-life data were obtained at each visit when feasible.
RESULTS
Among the 276 patients included in the analysis, the median age was 61 (range, 36-87) years; 247 (89.5%) were men; and 183 (66.3%) had less than 10 pack-years of smoking history. Most patients (251 [90.9%]) were White. Overall, 87 (31.5%) had cT3-cT4 disease and 65 (23.5%) had cN2-cN3 disease per the 8th edition of the American Joint Committee on Cancer Staging Manual. One hundred seventy-two patients (62.3%) completed 300-mg/m2 high-dose cisplatin therapy. During a median follow-up of 26 (range, 21-32) months, 8 patients developed locoregional recurrence, including 7 at the primary site or gross nodes that received a total dose of 70 Gy and 1 with a persistent node not previously identified as gross disease that received a total dose of only 30 Gy. The 24-month locoregional control was 97.0%; progression-free survival, 88.0%; distant metastasis-free survival, 95.2%; and overall survival, 95.1%. During treatment, 17 patients (6.2%) required a feeding tube. At 24 months, most of the QOL composite scores (jaw-related problems, pain, social contact, eating, speech, and swallow) were comparable or superior to baseline measures except for senses, dry mouth, muscular tension, and cognitive functioning, which improved over time but remained marginally worse than baseline.
CONCLUSIONS AND RELEVANCE
This cohort study found that the evaluated de-escalation strategy for elective regions showed favorable clinical outcomes and QOL profiles. Long-term follow-up data will help affirm the efficacy of this strategy as a care option for treating HPV-associated OPC with primary CCRT.
Topics: Adult; Aged; Aged, 80 and over; Alphapapillomavirus; Carcinoma; Chemoradiotherapy; Cohort Studies; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Quality of Life; Retrospective Studies
PubMed: 35050342
DOI: 10.1001/jamaoncol.2021.6416 -
The Journal of International Medical... Jun 2021Oropharyngeal squamous cell carcinoma (OPSCC) is a malignant tumor that occurs at the tongue base, soft palate, palatine tonsil, and pharyngeal wall. Few studies of...
OBJECTIVE
Oropharyngeal squamous cell carcinoma (OPSCC) is a malignant tumor that occurs at the tongue base, soft palate, palatine tonsil, and pharyngeal wall. Few studies of OPSCC have been performed in elderly patients.
METHODS
Patients with human papilloma virus (HPV)-related OPSCC were extracted from the Head and Neck with HPV Status Database of the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. We identified 355 patients with HPV-positive status, and we retrospectively evaluated elderly (≥65 years) and younger (30-64 years) patient groups to compare the differences.
RESULTS
Of the 355 patients who were diagnosed with HPV-related OPSCC, 113 constituted the elderly group. Comparing the elderly group with the younger group, the 3-year HPV-positive overall survival (OS) rates were 62.4% and 70.2%, respectively, and the 5-year OS rates were 50.4% and 59.2%, respectively. Cox regression analysis demonstrated that tumor (T) stage and chemotherapy were prognostic factors for OS.
CONCLUSION
Elderly patients with OPSCC had different clinicopathological characteristics. T stage and chemotherapy should be priorities when evaluating the OS of elderly patients with OPSCC.
Topics: Aged; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck
PubMed: 34082601
DOI: 10.1177/03000605211016662