Human Papillomavirus-associated Oropharyngeal Carcinoma Research Articles

Trends in the treatment of human papillomavirus-associated oropharyngeal carcinoma in Slovakia.

The optimal treatment of oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) is currently a subject of clinical research. This questionnaire study investigated current trends in the treatment of HPV-associated (HPV+) OPC in Slovakia with the incorporation of deintensification of oncological treatment into routine clinical practice outside of clinical trials. The Slovak Cooperative Head and Neck Cancer Group (SCHNCG) developed a questionnaire aimed at identifying trends in the oncological treatment of HPV+ OPC intended for all radiation oncology (RO) facilities in Slovakia. Specialists in the field of RO responded to general questions about the character of their individual institutions as well as to 4 theoretical clinical scenarios (case reports) regarding the treatment of HPV+ OPC, focusing primarily on the applied dose of radiotherapy (RT), the extent of target volumes, and the type of concurrent chemotherapy (CHT). The questionnaire study involved 35 RO specialists from 14 institutions in Slovakia. Regarding primary chemoradiotherapy (CRT) in T1N1M0 HPV+ OPC, 16 respondents (45.7%) would consider de-escalation of the RT dose to <70 Gy. In the case of postoperative RT in pT1pN1M0 HPV+ OPC with negative resection margins (R0) and absent extracapsular extension (ECE), 4 physicians (11.4%) would consider de-escalation of the RT dose to <60 Gy in the tumor bed area, while the majority of the treating specialists (n=19, 54.3%) would omit concurrent CHT. In the case of primary RT in elderly patient with T2N1M0 HPV+ OPC, the same number of physicians (n=16, 45.7%) would consider de-escalation of the RT dose to <70 Gy, and 14 respondents (40.0%) would completely omit CHT. In a high-risk patient with T2N3M0 HPV+ OPC with a complete response after 3 cycles of induction chemotherapy (iCHT), none of the respondents would indicate a reduction in the RT dose to the area of the original tumor and lymphadenopathy to <60 Gy. The doses and extent of irradiated volumes in the treatment of HPV+ OPC in Slovakia vary among different institutions. The tendency to de-escalate RT doses and reduce doses of concurrent systemic therapy in Slovakia is high and there was also an observed trend to reduce the extent of radiation treatment fields.

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.

Evaluation of Substantial Reduction in Elective Radiotherapy Dose and Field in Patients With Human Papillomavirus–Associated Oropharyngeal Carcinoma Treated With Definitive Chemoradiotherapy

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). 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). 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. 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. 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. 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. 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.

Fear of Cancer Recurrence in Survivors of Human Papillomavirus–Associated Oropharyngeal Carcinoma

To estimate the prevalence of and characteristics associated with fear of cancer recurrence (FCR) among human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) survivors. We conducted a cross-sectional study in HPV-OPC survivors ≥12 months from completion of definitive (chemo)radiation therapy (RT/CRT). Eligible patients completed the Fear of Cancer Recurrence Inventory short-form (FCRI-SF), the European Organisation for research and Treatment of Cancer QLQ-C30, MD Anderson Symptom Inventory-Head and Neck, and PROMIS Anxiety and Depression short forms. Associations between FCRI-SF scores and other variables were investigated using linear regression models. A total of 136 HPV-OPC survivors were enrolled; the median age was 61 years (range, 42-87 years), 84% were male, 72% were currently partnered, 83% were current nonsmokers, 67% were regular alcohol consumers, and the median time since treatment was 2.8 years (range, 1.0-5.5 years). Clinical levels of FCR (≥13) were observed in 72 of 135 patients (53%; 95% confidence interval [CI], 45%-62%). Characteristics significantly associated with increasing FCR scores were younger age (-0.9/5 years; 95% CI, -1.7 to -0.01; P = .031), lower global quality of life (-0.8/10 unit increase; 95% CI, -1.4 to -0.2; P=.012), higher symptom interference (0.8/unit increase; 95% CI, 0.1-1.5; P=.017), and a higher burden of anxiety (0.4/unit; 95% CI, 0.3-0.5; P <.001) and depression (0.3/unit; 95% CI, 0.1-0.4; P <.001). Other sociodemographic tumor- and treatment-related characteristics were not statistically significant. Compared with patients reporting nonclinical levels of FCR, significantly more patients reporting clinical levels of FCR than expected believed professional psychological assistance would have been beneficial (60% vs 33%; P = .002). Clinical levels of FCR were observed in approximately half of the HPV-OPC survivors. Survivors reporting higher FCR were younger with worse self-reported global quality of life and higher symptom interference and emotional distress. No other patient, tumor, or treatment factors were associated with higher FCR.

Oncologic Outcomes Following Transoral Robotic Surgery for Human Papillomavirus–Associated Oropharyngeal Carcinoma in Older Patients

While early epidemiologic studies ascribed increases in the incidence of human papillomavirus-associated oropharyngeal cancers to middle-aged patients, recent analyses have demonstrated an increasing median age of diagnosis. Treatment of patients older than 70 years is controversial as their inclusion in the practice-defining clinical trials has been limited and the survival benefit conferred by chemotherapy may be outweighed by treatment toxic effects. To assess the oncologic outcomes of older adults with human papillomavirus-associated oropharyngeal cancer who underwent upfront transoral robotic surgery and pathologic characteristics-guided adjuvant therapy in a large cohort of patients with close follow-up. A retrospective cohort analysis was conducted in a tertiary care academic medical center between January 1, 2010, and December 30, 2017. Patients aged 70 years or older at time of diagnosis with biopsy-proven and surgically resectable p16-positive oropharyngeal cancers were included. Data analysis was conducted from March 1 to June 1, 2020. Transoral robotic surgery oropharyngeal resection and neck dissection with pathologic characteristic-guided adjuvant therapy. Three-year estimates of disease-specific survival, overall survival, and disease-free survival, as well as rates of adjuvant therapy (radiotherapy and chemoradiotherapy) and perioperative complications. Seventy-seven patients were included (median age, 73.0; interquartile range, 71.0-76.0; range, 70-89 years); of these, 58 were men (75.3%). Perioperative mortality was 1.3% and the rate of oropharyngeal hemorrhage was 2.6%. Twenty-seven patients (35.1%) underwent postoperative radiotherapy and 20 patients (26.0%) underwent postoperative chemoradiotherapy. The median length of follow-up was 39.6 (range, 0.1-96.2) months, and the 3-year estimates of survival were 92.4% (95% CI, 82.4%-96.9%) for disease-specific survival, 90.0% (95% CI, 79.4%-95.0%) for overall survival, and 84.3% (95% CI, 73.4%-91.0%) for disease-free survival. The findings of this cohort study suggest that transoral robotic surgery and pathologic characteristic-guided adjuvant therapy can provide beneficial survival outcomes, infrequent perioperative mortality, and, for most carefully selected older adults, obviate the need for chemotherapy.

Reducing the Radiation Therapy Dose Prescription for Elective Treatment Areas in Human Papillomavirus–Associated Oropharyngeal Carcinoma Being Treated With Primary Chemoradiotherapy at Memorial Sloan Kettering Cancer Center

AbstractData on the biology and radiosensitivity of human papillomavirus–related cancers have led many expert radiation oncologists to decrease the radiation dose to target areas in selected situations. At Memorial Sloan Kettering Cancer Center, we have altered our radiation guidelines to allow substantial dose reduction to elective treatment regions and to omit radiation completely in other regions that have historically been included in the elective treatment volume. Here we summarize our current dose prescriptions and briefly explain the rationale behind these choices, which we anticipate will change when additional data mature. These recommendations are based on the American Joint Committee on Cancer seventh edition TNM Staging System and applicable only to patients who receive concurrent platinum-based chemotherapy and in whom both p16 immunohistochemistry and human papillomavirus RNA in situ hybridization tests are positive.

Human papillomavirus-associated oropharyngeal carcinoma: trends in epidemiology and methods for detecting the virus in tumors

Oropharyngeal squamous cell carcinoma has been traditionally associated with tobacco and alcohol consumption. Nevertheless, latter 30 years have shown squamous cell carcinoma (OPSCC) incidence stagnation and increasing, despite the decrease in smoking prevalence. The incidence was recognized among white men of middle age, often non-smokers or former smokers in the investigations with smoking cessation data. It differs from traditional patient with OPSCC, older men, heavy smoker or alcohol drinker. The incidence of OPSCC is increased due human papilloma virus (HPV) infection. The infection transition is associated with sex and oro-genital contact may lead to HPV-infection of oropharynx and oral cavity. There are multiple types of HPV, but the majority of OPSCC is associated with HPV 16 type. Epidemiology of HPV-associated OPSCC, HPV-infection of oral cavity and/or oropharynx and HPV detection are discussed in the review.

Sparing Level IB in Node-Positive, Human Papillomavirus–Associated Oropharyngeal Carcinoma: An Early Safety and Efficacy Analysis

Sparing Level IB in Node-Positive, Human Papillomavirus–Associated Oropharyngeal Carcinoma: An Early Safety and Efficacy Analysis

Sparing Level IB in Node-Positive, Human Papillomavirus–Associated Oropharyngeal Carcinoma: An Early Safety and Efficacy Analysis

Sparing Level IB in Node-Positive, Human Papillomavirus–Associated Oropharyngeal Carcinoma: An Early Safety and Efficacy Analysis

Postoperative Radiation Therapy for Human Papillomavirus–Associated Oropharyngeal Carcinoma

Postoperative Radiation Therapy for Human Papillomavirus–Associated Oropharyngeal Carcinoma

Characteristics and kinetics of cervical lymph node regression after radiation therapy for human papillomavirus-associated oropharyngeal carcinoma: Quantitative image analysis of post-radiotherapy response

We sought to characterize the pattern of lymph node regression and morphology following definitive radiation therapy (RT) for human papilloma virus (HPV)-associated oropharyngeal carcinoma in patients with disease control. Radiographically positive cervical lymph nodes from patients treated with definitive RT for HPV-associated oropharyngeal carcinoma were segmented on initial pre- and subsequent post-RT contrast enhanced CT images. Pre-specified quantitative nodal parameters were calculated. Initial nodal parameter correlates of final nodal size, final nodal volume, and time to <1 cm short-axis diameter were determined. Sixty-six radiographically positive lymph node were analyzed in 36 patients. Lymph nodes exhibited initial volume decreases with size stabilization at ∼4 months. Fifteen nodes (23%) underwent complete radiographic response (median 6.4 months following RT; range 2.9-25.6 months). On multivariate time-to-event analysis, initial hypodense/fat component, nodal volume, and short-axis diameter exhibited inverse association, while higher HU standard deviation exhibited a positive association, with reaching <1 cm short-axis diameter (all p<0.05). Our results showed a substantial decrease in nodal volume within the first 1-2 months following RT. These findings support our current nodal imaging paradigm, propose a quantitative methodology, and describe a reference dataset for further validation and comparison studies.

Histological subtypes and characteristic structures of HPV-associated oropharyngeal carcinoma; study with Japanese cases

BackgroundHuman papillomavirus-associated oropharyngeal carcinoma (HPV-OPC) is clinicopathologically distinct entity from the HPV-unassociated one (nHPV-OPC). This study aimed to determine the relationship between histological subtypes of OPC and HPV status for Japanese cases and to identify histological structures of HPV-OPC.Methods66 OPC cases were categorized into conventional squamous cell carcinoma (SCC) and the variants. Conventional SCC was subcategorized into keratinizing (KSCC), non-keratinizing (NKSCC), and hybrid SCC (HSCC). HPV status of all cases was determined using p16-immunohistochemistry and HPV-DNA ISH.ResultsTwo histological subtypes, NKSCC and HSCC, tended to be HPV-OPC and KSCC tended to be nHPV-OPC with statistical significance. Two histological structures, abrupt keratinization, defined in the text, and comedo-necrosis among non-maturing tumor island, were observed for 58.1% and 38.7% of HPV-OPC, and tended to exist for HPV-OPC with statistical significance.ConclusionsThis study showed the association of NKSCC/HSCC with HPV-OPC in Japanese cases, and two histological structures, abrupt keratinization and comedo-necrosis among non-maturing island, were considered characteristic histological features of HPV-OPC.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1816432541113073.

Retrospective review of positron emission tomography with contrast-enhanced computed tomography in the posttreatment setting in human papillomavirus-associated oropharyngeal carcinoma.

To determine the value of positron emission tomography (PET) with contrast-enhanced computed tomography (CT) in assessing the need for neck dissection by retrospectively reviewing the pathology reports of patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC). Retrospective cohort study. Tertiary medical center. Seventy-seven patients with HPV-related SCC. Seventy-seven consecutive patients with a diagnosis of HPV-related SCC who were treated with radiotherapy as the primary treatment between August 2007 and October 2010 were retrospectively evaluated for radiologic and pathologic rate of persistence of nodal metastasis after completion of definitive radiotherapy. Pretreatment and posttreatment imaging included contrast-enhanced CT and PET. Response to treatment was measured on CT, PET at standardized uptake value (SUV) thresholds of 2 and 2.5, and PET/CT by a neuroradiologist in a blinded fashion. Then, the pathology report of the patients who underwent neck dissections was reviewed for nodal status after resection and correlated with the imaging findings. Of the 77 patients, 67 met the study criteria, with an average follow-up PET/CT scan at 90.5 days after completion of radiotherapy. Ten patients did not undergo follow-up PET/CT imaging. Twenty patients underwent neck dissections after completion of radiation therapy. Of these 20 patients, 4 had persistent tumor and 16 did not have viable tumor. Using the final pathology report to correlate with imaging responses, CT had a negative predictive value (NPV) of 85.7% (95% CI, 48.7%-97.4%), PET with SUV thresholds of 2 had an NPV of 91.7% (95% CI, 64.6%-98.5%), PET with a cutoff SUV of 2.5 had an NPV of 85.7% (95% CI, 60.1%-96.0%), PET/CT with an SUV of 2 had an NPV of 100% (95% CI, 59.8%-100.0%), and PET/CT with an SUV of 2.5 had an NPV of 85.7% (95% CI, 48.7%-97.4%). The 47 patients who did not undergo neck dissection had a median follow-up of 26 months without an isolated neck failure. Analysis of all 67 patients in the cohort revealed the following values: CT had an NPV of 95.7% (95% CI, 85.8%-98.8%), PET with an SUV of 2 had an NPV of 98.2% (95% CI, 90.4%-99.7%), PET with an SUV of 2.5 had an NPV of 95.0% (95% CI, 86.3%-98.3%), PET/CT with an SUV of 2 had an NPV of 100.0% (95% CI, 92.0%-100.0%), and PET/CT with an SUV of 2.5 had an NPV of 95.7% (95% CI, 85.8%-98.8%). Positron emission tomography combined with contrast-enhanced CT has a better NPV than either imaging modality alone in patients with HPV-associated oropharyngeal SCC. Furthermore, PET/CT with an SUV threshold of 2 used in patients with HPV-related SCC offers an imaging modality with a high NPV that may obviate the need for unnecessary neck dissections.