Human Papillomavirus-associated Oropharyngeal Cancer Research Articles

Comparison of Induction Cisplatin, Docetaxel, and 5-Fluorouracil to An Induction Platinum Doublet Regimen for Locally Advanced Human Papillomavirus-Associated Oropharyngeal Cancer

Comparison of Induction Cisplatin, Docetaxel, and 5-Fluorouracil to An Induction Platinum Doublet Regimen for Locally Advanced Human Papillomavirus-Associated Oropharyngeal Cancer

Sexual Behavior and Perceived Risk for Oropharyngeal Cancer Among Men Who Have Sex With Men: A Psychometric Scale Validation.

Men who have sex with men (MSM) are at increased risk for human papillomavirus-associated oropharyngeal cancer (HPV-OPC). The objective of this analysis was to create a psychometrically validated scale to measure perception of risk for HPV-OPC. We conducted an exploratory and a confirmatory factor analysis to determine and confirm the latent factor structure. We used a path diagram to evaluate the relationship between the validated scale and perceived risk for HPV-OPC. The model was determined to be a good fit if it met all criteria: root mean square error of approximation ≤0.06, standardized root mean residual ≤0.08, Comparative Fit Index ≥0.90, and Tucker-Lewis Index ≥0.90. We report standardized estimates and 95% confidence intervals. This cross-sectional study recruited 1315 MSM. A majority (73.33%) of MSM had performed fellatio on ≥20 partners, 36.98% had rimmed ≥20 partners, and 5.31% had performed cunnilingus on ≥10 partners in their lifetime.Six sexual history survey items loaded onto 2 latent factors: sexual risk behaviors: class 1 and sexual risk behaviors: class 2. The final model statistics indicated good fit: root mean square error of approximation = 0.064, standardized root mean residual = 0.059, Comparative Fit Index = 0.996, and Tucker-Lewis Index = 0.993. Sexual risk behaviors: class 1 was associated with greater perceived risk for HPV-OPC (0.217; 95% confidence interval, 0.138-0.295). Age, HIV status, HPV vaccination status, and sexual risk behaviors: class 2 were not associated with perceived risk for HPV-OPC. Men who have sex with men assessed risk for HPV-OPC based on their lifetime number of cisgender male sexual partners, rimming partners, and fellatio partners but not other sexual behaviors. Men who have sex with men may be responsive to future HPV-OPC educational interventions and opportunities for screening.

Capecitabine for Salvage Treatment of Patients With Heavily Pretreated Human Papillomavirus-Associated Oropharynx Cancer With Distant Metastases.

Patients with metastatic human papillomavirus-associated oropharyngeal cancer (HPV-OPC) have a median overall survival exceeding 2 years and are often candidates for multiple lines of palliative therapy. With the approval of immunotherapy as first-line treatment, salvage therapeutic options are limited. We describe our experience using capecitabine as salvage therapy for patients with recurrent or metastatic (R/M) HPV-OPC. We performed a retrospective study of patients with R/M HPV-OPC with distant metastatic disease. Eligible patients were identified from a medical oncology clinical database. Demographic and clinical data were abstracted from the medical record. Survival probabilities were estimated with the Kaplan-Meier method. 10 patients were identified. Sites of metastatic disease included lung, liver, mediastinal lymph nodes, bone, abdominal lymph nodes, and soft tissue. Most patients received capecitabine as fourth-line treatment. The median duration from start of capecitabine therapy until death was 10.5 months. Best treatment response was as follows: partial responses (PR) were seen in 4 of 10 (40%), stable disease (SD) in 3 of 10 (30%), and progressive disease (PD) in 2 of 10 (20%). The clinical benefit rate (CR + PR + SD) was 70%. Reasons for discontinuation included disease progression (n = 8) and side effects (n = 2). One patient notably had prolonged benefit from capecitabine and continued to be on treatment for 34 months total. Capecitabine is a potential salvage treatment for heavily pretreated patients with R/M HPV-OPC, with some patients experiencing prolonged response. Clinical or molecular predictors of response would be helpful to identify patients likely to benefit; a larger prospective study would be useful to confirm efficacy in this patient population.

A Longitudinal Study Evaluating Sexual Health Outcomes and Prioritization in Patients Undergoing Chemoradiation for Human Papillomavirus-Associated Oropharyngeal Cancer

PurposeThe primary objectives were to describe the longitudinal course of sexual health in people undergoing curative (chemo)radiotherapy ([C]RT) for human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPVOPSCC) and identify factors associated with higher sexual satisfaction 12 months after [C]RT. MethodsEligible participants from three sites were recruited to a prospective observational study between October 2020 and November 2021. Measures of sexual health (QLQ-SHQ22), treatment outcome priorities (Chicago priorities scale), quality of life (QLQ-C30), symptom burden (MDASI-HN), emotional distress (PROMIS), and facial appearance and appearance distress (FACE-Q) were administered before, at the end and three and 12 months after [C]/RT. ResultsOf 128 eligible participants, 100 were recruited; sexual health measure data was available for 89 of 98 patients alive at 12 months. Mean sexual satisfaction scores were 51.8 (SD=26.6) before [C]RT. Mixed model results indicated a clinically significant reduction in sexual satisfaction by the end of (-25.4, 95% CI -30.7 to -20.2) and three months after [C]RT (-12.2, -17.3 to -7.0), but not 12 months after [C]RT (-3.8, 95% CI -9.0 to 1.4). Of 13 treatment outcome priorities, ‘keeping sexual function’ had a median rank of 10 and 9 before and 12 months after [C]RT, respectively; 24% and 26% identified it as a top priority at these times. Cohabiting, having a sexual partner, being sexually active, higher global health status, lower sexual health issues, lower depression, and considering sexual function a top priority were associated with higher sexual satisfaction scores 12 months after [C]RT. ConclusionsWhile affected acutely by [C]RT, average sexual satisfaction returns to near pre-treatment levels after 12 months. Sexual function is considered a ‘top’ survivorship priority by approximately one-quarter of HPVOPSCC patients.

Fear of Cancer Recurrence (FCR) in Human Papillomavirus-Associated Oropharyngeal Cancer (HPVOPC) Patients 12 months (12m) after (Chemo)Radiation (RT/CRT)

This study constitutes a planned secondary endpoint analysis from a longitudinal unmet needs study. The aim was to: (1) describe FCR outcomes 12m after RT/CRT; (2) examine associations between FCR severity scores 12m after RT/CRT and patient and disease characteristics and other patient-reported outcomes (PROs); and (3) to evaluate preferred FCR referral pathways. Eligible HPVOPC patients scheduled for curative RT/CRT were approached for enrolment. FCR was assessed with the 42-item Fear of Cancer Recurrence Inventory (FCRI) 12m after RT/CRT, as were patients' preferences for FCR referral pathways, using customized questions. Optimism (LOT-R) and resilience (Connor-Davidson Resilience Scale) were assessed at enrolment. Health-related quality of life (HRQL, EORTC QLQ-C30), disease-specific symptom severity and interference (MDASI-HN) and emotional distress (PROMIS Anxiety 7a, Depression 8a) were assessed 12m after RT/CRT. A total of 100/129 eligible patients were enrolled between October 2020 and November 2021. 85/93 (91%) alive patients without recurrence completed the FCRI; patients were mostly men (n = 73, 86%), with a median age of 60 years (range 44-77). A majority had stage I disease (n = 46, 54%) and received CRT (n = 82, 96%). The mean FCRI total score was 45.4 (SD = 26.3, range 0-102, possible range 0-168). The mean FCRI severity score was 12.1 (SD = 7.4, median = 11.0, range 0-29); 13%, 31% and 56% of respondents scored in the severe (≥22), moderate (>12-22) and low (≤12) range, respectively. Univariable regression analysis indicated that lower resilience, lower HRQL (global health status, all functional domains), higher emotional distress (anxiety, depression), and higher symptom severity and interference were associated with higher FCR severity scores 12m after RT/CRT. Apart from lower levels of education, associations between FCRI severity scores and other patient and disease factors were not statistically significant. If FCR had been a problem (n = 66), 86%, 44%, 14% and 5% of patients indicated they would like to discuss it with their oncologist, primary care physician, a psychologist or nurse, respectively (multiple responses allowed). If specific FCR interventions were available, 70/85 indicated their preferred sources for delivery (ordered by median rank) were oncologist, primary care physician, psychologist or nurse (tied), self-management or group sessions (tied). Almost half of HPVOPC patients reported moderate-to-severe FCR 12m after RT/CRT. Increased FCR severity was associated with education and self-reported resilience at baseline and with other measures of HRQL, toxicity and emotional distress at 12m. While patients view oncologists as central in FCR management, education about the benefits of other FCR-reducing approaches may be necessary.

Performance of Liquid Biopsy for Diagnosis and Surveillance of Human Papillomavirus–Associated Oropharyngeal Cancer

There is growing interest in the use of circulating plasma tumor human papillomavirus (HPV) DNA for diagnosis and surveillance of patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Recent advances in the assays, combining the identification of circulating HPV tumor DNA and tumor DNA fragment analysis (tumor tissue-modified viral [TTMV]-HPV DNA), have been shown to be highly accurate. However, use of these newer techniques has been limited to small cohort studies and clinical trials. To establish the clinical efficacy of plasma TTMV-HPV DNA testing in the diagnosis and surveillance of HPV-associated OPSCC in a contemporary clinical setting. This retrospective observational cohort study included patients with OPSCC who underwent TTMV-HPV DNA testing between April 2020 and September 2022 during the course of routine clinical care. For the diagnosis cohort, patients with at least 1 TTMV-HPV DNA measurement prior to initiation of primary therapy were included. Patients were included in the surveillance cohort if they had at least 1 TTMV-HPV DNA test performed after completion of definitive or salvage therapy. Per-test performance metrics, including sensitivity, specificity, positive predictive value, and negative predictive value, for TTMV-HPV DNA testing. Of 399 patients included in the analysis, 163 were in the diagnostic cohort (median [IQR] age, 63 [56-68.5] years; 142 [87.1%] male), and 290 were in the surveillance cohort (median [IQR] age, 63 [57-70] years; 237 [81.7%] male). Of the 163 patients in the diagnostic cohort, 152 (93.3%) had HPV-associated OPSCC while 11 (6.7%) had HPV-negative OPSCC. The TTMV-HPV DNA sensitivity in pretreatment diagnosis was 91.5% (95% CI, 85.8%-95.4% [139 of 152 tests]), and the specificity was 100% (95% CI, 71.5%-100% [11 of 11 tests]). In the surveillance cohort, 591 tests conducted in 290 patients were evaluated. A total of 23 patients had molecularly confirmed pathologic recurrences. The TTMV-HPV DNA test demonstrated sensitivity of 88.4% (95% CI, 74.9%-96.1% [38 of 43 tests]) and specificity of 100% (95% CI, 99.3%-100% [548 of 548 tests]) in detecting the recurrences. Positive predictive value was 100% (95% CI, 90.7%-100% [38 of 38 tests]), and negative predictive value was 99.1% (95% CI, 97.9%-99.7% [548 of 553 tests]). The median (range) lead time from positive TTMV-HPV DNA test to pathologic confirmation was 47 (0-507) days. This cohort study demonstrated that when evaluated in a clinical setting, the TTMV-HPV DNA assay demonstrated 100% specificity in both diagnosis and surveillance. However, the sensitivity was 91.5% for the diagnosis cohort and 88.4% for the surveillance cohort, signifying that nearly 1 in 10 negative tests among patients with HPV-associated OPSCC was a false negative. Additional research is required to validate the assay's performance and, if validated, then further research into the implementation of this assay into standard clinical practice guidelines will be required.

Post-treatment 18F-fludeoxyglocuse-positron emission tomography in human papillomavirus-associated oropharyngeal cancer.

Human papillomavirus association has changed the landscape of treatment for oropharyngeal squamous cell carcinoma; it remains to be seen whether current post-treatment surveillance schedules are effective. Evaluate whether post-treatment surveillance of oropharyngeal cancer through FDG-PET imaging is modified by human papillomavirus association. A prospective cohort analysis of retrospective data was conducted for patients undergoing treatment of oropharyngeal cancer between 2016 and 2018. This study was conducted at a single large tertiary referral center in Brisbane, Australia. Two-hundred and twenty-four patients were recruited for the purposes of the study, 193 (86%) with HPV-associated disease. In this cohort FDG-PET had a sensitivity of 48.3%, specificity of 72.6%, positive predictive value of 23.7%, and negative predictive value of 88.8% in detecting disease recurrence. FDG-PET in HPV-associated oropharyngeal cancer has significantly lower positive predictive value when compared to non-HPV-associated oropharyngeal cancer. Caution should be used when interpreting positive post-treatment FDG-PET.

Patient-Reported Symptom Severity, Health-Related Quality of Life, and Emotional Distress Trajectories During and After Radiation Therapy for Human Papillomavirus–Associated Oropharyngeal Cancer: A TROG 12.01 Secondary Analysis

This secondary analysis of clinical trial TROG 12.01, involving patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma, aimed to identify patient-reported outcome (PRO) trajectories before, during, and after chemoradiotherapy. Head and neck cancer symptom severity (HNSS) and interference (HNSI), generic health-related quality of life (HRQL), and emotional distress were assessed with the MD Anderson Symptom Inventory-Head and Neck, Functional Assessment of Cancer Therapy-General, and Hospital Anxiety and Depression Scale questionnaires, respectively. Latent class growth mixture modeling (LCGMM) was used to identify distinct underlying trajectories. Baseline and treatment variables were compared between trajectory groups. The LCGMM identified latent trajectories for all PROs: HNSS, HNSI, HRQL, anxiety, and depression. Four HNSS trajectories (HNSS1-4) were identified, distinguished by differences in HNSS at baseline, during the peak of treatment symptoms, and during early and intermediate recovery. All trajectories were stable beyond 12 months. The reference trajectory (HNSS4, n=74) score was 0.1 (95% confidence interval [CI], 0.1-0.2) at baseline, peaking at 4.6 (95% CI, 4.2-5.0), with rapid early recovery (1.1; 95% CI, 0.8-2.2) and gradual improvement to 12 months (0.6; 95% CI, 0.5-0.8). Patients in HNSS2 (high baseline, n=30) reported higher baseline scores (1.4; 95% CI, 0.8-2.0) but were otherwise similar to HNSS4. Patients in HNSS3 (low acute, n=53) reported reduced acute symptoms (2.5; 95% CI, 2.2-2.9) with stable scores beyond 9 weeks after chemoradiotherapy (1.1; 95% CI, 0.9-1.4). Patients in HNSS1 (slow recovery, n=25) had slower recovery from an acute peak of 4.9 (95% CI, 4.3-5.6) to 0.9 (95% CI, 0.6-1.3) at 12 months. Age, performance status, education, receipt of cetuximab, and baseline anxiety varied between trajectories. The other PRO models demonstrated clinically relevant trajectories, with distinct associations with baseline factors. LCGMM identified distinct PRO trajectories during and after chemoradiotherapy. These and their associations with variations in the characteristics and treatment factors of patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma provide clinically relevant insights into identifying patients who may require increased support before, during, or after chemoradiotherapy.

Top advances of the year: Head and neck cancer.

Advances in treatment deintensification for human papillomavirus-associated oropharyngeal cancer include use of transoral surgery to permit reduction in pathologic risk-based postoperative therapy after transoral resection. The E3311 cooperative group trial demonstrated 3-year progression-free survival (PFS) of 95% for intermediate risk patients treated with 50Gy radiation alone, with no decrement for those with a smoking history. Favorable risk patients could be observed, with a 3-year PFS of 93%. Reduction in radiation dose is also feasible for favorable risk patients (low or no smoking history and low stage) treated with chemoradiation on the NRG HN002 trial, where 2-year PFS was 90.7%. For those favorable risk patients treated with radiation alone, 2-year PFS was 87.7% and this arm did not meet criteria for further testing. Important phase 3 trials of immunotherapy in first-line treatment of recurrent and/or metastatic head and neck cancer were also reported in 2022. For patients with nonnasopharyngeal sites of disease, the combination of the programmed death-1-directed antibody nivolumab plus the anti-CTLA-4 agent ipilimumab was not superior to chemotherapy plus cetuximab in the Checkmate 651 trial. However, in an important breakthrough for patients with nasopharyngeal cancer, the JUPITER-02 trial, conducted in China, Singapore, and Taiwan among patients with predominantly Epstein-Barr virus-related cancers, demonstrated a significant improvement in PFS (hazard ratio, 0.52) when toripalimab was added to gemcitabine/cisplatin chemotherapy. Immature survival data indicate overall survival will likely also be impacted.

Treatment Deintensification for Human Papillomavirus-Associated Oropharyngeal Cancer: Focused Review of Published Data

Human papillomavirus (HPV) is a causative agent for a subset of oropharyngeal cancer (OPC). The current standard of care (SOC) for locally advanced OPC is 70 Gy definitive radiotherapy (RT) concurrent with cisplatin, which entails significant proportions of acute and late grade 3 or higher toxicities. Accordingly, discovery of favorable prognosis of HPV-related OPC has led to enthusiasm to attenuate subspecialties therapy in multidisciplinary treatment. Diverse deintensification strategies were investigated in multiple phase 2 trials with an assumption that attenuated treatments result in comparable oncologic outcome and less toxicities compared with SOC. Several trials on chemotherapy deintensification revealed that concomitant administration of cisplatin is not to be omitted or substituted for cetuximab without compromising progression-free survival or local control. A transoral robotic surgery (TORS) is investigated as alternative local treatment, but TORS plus SOC or mild deintensified adjuvant RT showed similar toxicities and inferior oncologic outcomes compared with SOC definitive RT or moderately deintensified RT. However, it has been reported that TORS plus deintensified 30-36 Gy adjuvant RT results in excellent outcome and less late toxicity compared with SOC adjuvant RT. Several phase 2 trials reported apparently equivalent progression-free survival and local control and similar adverse effects with moderately deintensified 60 Gy RT compared with SOC 70 Gy RT. Further dose reduction below 60 Gy has been investigated using biology-directed approaches, which use response to induction chemotherapy or metabolic images to triage HPV-positive OPC for deintensified RT. In summary, these trials provide valuable insights for future directions. Available evidence consistently showed that moderately deintensified RT is effective and safe for HPV-positive OPC in both definitive and adjuvant settings. Concurrent cisplatin remains an essential component without which progression-free survival is significantly compromised for advanced HPV-positive OPC. A simple incorporation of TORS to SOC may be detrimental for oncologic outcome without anticipated toxicity reduction. Given the lack of level 1 evidence, it is prudent to curb an unjustified deviation from the current SOC and limit any deintensified strategies to clinical trials and adhere to the current SOC.

Human Papillomavirus-Directed Therapeutics for Human Papillomavirus-Associated Oropharyngeal Cancer.

Despite the availability of prophylactic human papillomavirus (HPV) vaccines, there is a growing incidence of HPV-associated head and neck squamous cell carcinomas (HPV-HNSCC) worldwide. The viral etiology of HPV-HNSCC provides an opportunity to develop personalized immune-based therapies, which target the unique viral- or tumor-specific proteins. Novel HPV-targeted immunotherapeutic approaches in clinical development are reviewed. Early results from these trials highlight new opportunities and potential challenges ahead. Immunotherapies for HPV-associated HNSCCs will require a tailored combinatorial approach based on preexisting mechanisms of host immune resistance. As the field continues to identify the relevant HPV types 16 and 18 immunogenic epitopes that are presented by diverse HLA class I alleles, improved HPV-targeted biologics and clinical monitoring tools can be developed and applied to a broader cancer patient population.

The Number of Radiographically Positive Lymph Nodes Further Stratifies Patient Survival Among Clinical N1 Patients With Human Papillomavirus–Associated Oropharyngeal Cancer

PurposeHuman papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV[+]OPSCC) requires further study to optimize the existing clinical staging system and guide treatment selection. We hypothesize that incorporation of the number of radiographically positive lymph nodes will further stratify patients with clinical N1 (cN1) HPV(+)OPSCC. Methods and MaterialsA post hoc analysis from 2 prospective clinical trials at a high-volume referral center was conducted. Patients underwent primary tumor resection and lymphadenectomy, followed by either standard-of-care radiation therapy (60 Gy in 30 fractions) with or without cisplatin (40 mg/m2 weekly) or de-escalated radiation therapy (30 Gy in 20 twice-daily fractions) with concomitant 15 mg/m2 docetaxel once weekly. Imaging studies were independently reviewed by a blinded neuroradiologist classifying radiographic extranodal extension (rENE) and the number and maximal size of involved lymph nodes. Patients without pathologic data available for assessment were excluded. ResultsA total of 260 patients were included. Of these, 216 (83%) were cN1. Patients had a median of 2 radiographically positive lymph nodes (range, 0-12), and 107 (41%) had rENE. For cN1 patients, stratifying by radiographically positive lymph nodes (1-2 vs 3-4 vs >4) was predictive of progression-free survival (PFS) (P = .017), with 2-year PFS rates of 96%, 88%, and 81%, respectively. More than 2 radiographically positive lymph nodes was identified as a significant threshold for PFS (P = .0055) and overall survival (P = .029). Radiographic ENE and lymph node size were not predictive of PFS among cN1 patients. ConclusionsThe number of radiographically positive lymph nodes is predictive of PFS and overall survival and could be used to meaningfully subcategorize cN1 patients with HPV(+)OPSCC. We recommend further validation of our proposal that cN1 patients with 1 to 2 radiologically positive lymph nodes be categorized as cN1a, patients with 3 to 4 radiologically positive lymph nodes categorized as cN1b, and patients with >4 radiographically positive lymph nodes categorized as cN1c.

Estimated Cost of Circulating Tumor DNA for Posttreatment Surveillance of Human Papillomavirus–Associated Oropharyngeal Cancer

Estimated Cost of Circulating Tumor DNA for Posttreatment Surveillance of Human Papillomavirus–Associated Oropharyngeal Cancer

Risk and response adapted de-intensified treatment for HPV-associated oropharyngeal cancer: Optima paradigm expanded experience

BackgroundFavorable prognosis for Human papillomavirus-associated (HPV+) oropharyngeal cancer (OPC) led to investigation of response-adaptive de-escalation, yet long-term outcomes are unknown. We present expanded experience and follow-up of risk/response adaptive treatment de-intensification in HPV+ OPC. MethodsA phase 2 trial (OPTIMA) and subsequent cohort of sequential off-protocol patients treated from September 2014 to November 2018 at the University of Chicago were reviewed. Eligible patients had T3-T4 or N2-3 (AJCC 7th edition) HPV+ OPC. Patients were stratified by risk: High-risk (HR) (T4, ≥N2c, or >10PYH), all others low-risk (LR). Induction chemotherapy (IC) included 3 cycles of carboplatin and nab-paclitaxel (OPTIMA) or paclitaxel (off-protocol). LR with ≥50% response received low-dose radiotherapy (RT) alone to 50 Gy (RT50). LR with 30–50% response and HR with ≥50% response received intermediate-dose chemoradiotherapy (CRT) to 45 Gy (CRT45). All others received full-dose CRT to 75 Gy (CRT75). Results91 patients consented and 90 patients were treated, of which 31% had >10PYH, 34% had T3/4 disease, and 94% had N2b/N2c/N3 disease. 49% were LR and 51% were HR. Overall response rate to induction was 88%. De-escalated treatment was administered to 83%. Median follow-up was 4.2 years. Five-year OS, PFS, LRC, and DC were 90% (95% CI 81,95), 90% (95% CI 80,95), 96% (95% CI 90,99), and 96% (88,99) respectively. G-tube placement rates in RT50, CRT45, and CRT75 were 3%, 33%, and 80% respectively (p < 0.05). ConclusionRisk/response adaptive de-escalated treatment for an inclusive cohort of HPV+ OPC demonstrates excellent survival with reduced toxicity with long-term follow-up.

Symptom burden, quality of life, functioning and emotional distress in survivors of human papillomavirus associated oropharyngeal cancer: An Australian cohort

BackgroundThis cross-sectional study examines patient-reported outcomes and functioning-based subgroups in human papillomavirus-associated oropharyngeal cancer survivors treated with chemoradiotherapy ≥12 months prior. MethodSurvivors completed EORTC QLQ-C30, MDASI-HN and PROMIS-Emotional distress questionnaires. Subgroups were identified via two-step clustering of QLQ-C30 functioning scales. Results136 patients were enrolled. Clinicians’ graded 19/136 (14%) patients as having at least one severe (Grade 3 CTCAE) toxicity, whereas 68/136 (50%) patients self-reported at least one toxicity in the severe range (MDASI-HN ≥ 7). QLQ-C30 Global health status score (mean 76, SD = 20) was comparable to population norms. Rates of moderate/severe anxiety (10%/1%) and depression (4%/1%) were low. Two functioning-based subgroups were formed based on auto-clustering statistics: high- (n = 93) and low-functioning (n = 41). Differences on all functioning scales were large (d: 1.57–2.29), as were differences on the remaining QLQ-C30 scales/items, most MDASI-HN symptom severity/interference scales, and PROMIS scales (d: 0.80–2.03). Differences and associations with patient/clinical characteristics were not significant. ConclusionIn this Australian cohort of HPV-OPC survivors there was significant discordance between clinician- and patient-reported toxicity. We observed population comparable global quality of life and low rates of emotional distress. However, we identified a low-functioning subgroup reporting significantly worse outcomes on a range of patient-reported measures who may benefit from targeted support.

Gastrostomy tube dependence and patient-reported quality of life outcomes based on type of treatment for human papillomavirus-associated oropharyngeal cancer: Systematic review and meta-analysis.

We examined the impact of treatment modality on gastrostomy tube dependence and patient-reported outcomes in human papillomavirus-associated oropharyngeal cancer (HPV-OPSCC). We performed systematic review and meta-analysis of functional outcomes 1-3 years after treatment. Twenty-three studies were included, reporting on 3127 patients treated for HPV-OPSCC. Gastrostomy tube dependence failed to show statistically significant difference between surgery with adjuvant therapy and chemoradiotherapy with cisplatin at 12 months (8.3% [95% CI: 3.1-15.9] vs. 4.2% [1.1-9.2], p=0.37) and 24-36 months (10.5% [95% CI: 3.2-21.5] vs. 3.3% [2.0-4.9], p=0.06). Surgery with adjuvant therapy was associated with worse University of Washington Quality of Life (UW-QOL) Swallowing (84 [95% CI: 80-88] vs. 89 [87-90], p=0.03) and UW-QOL Overall scores (76 [95% CI: 72-80] vs. 84 [81-86], p=0.001) compared to chemoradiotherapy with cisplatin at 12 months. Surgery with adjuvant therapy was associated with worse performance on certain measures of patient-reported swallow and overall function compared to chemoradiotherapy with cisplatin. Further randomized controlled trials are needed to directly compare functional outcomes after treatment for HPV-OPSCC.

Disease Profile and Oncologic Outcomes After Delayed Diagnosis of Human Papillomavirus-Associated Oropharyngeal Cancer.

Diagnostic delay in human papillomavirus-associated oropharynx squamous cell carcinoma (HPV(+)OPSCC) is common due to nonspecific symptoms. We aim to describe the disease burden and oncologic outcomes of patients with HPV(+)OPSCC diagnosed >12 months after symptom onset. This is a retrospective cohort study of HPV(+)OPSCC patients receiving intent-to-cure treatment (including surgery ± adjuvant therapy or primary chemoradiation). 2006-2016, tertiary care center. Tumor stage was compared between patients with and without delayed diagnosis using χ2 tests. Kaplan-Meier survival analysis with univariate and multivariable Cox regressions were used to determine the effect of diagnostic delay on oncologic outcomes. In total, 664 patients were included. Compared to patients diagnosed <12 months from symptom onset (n = 601), those diagnosed at >12 months (n = 63) were more likely to have T4 disease and higher overall American Joint Committee on Cancer (AJCC) clinical stage at presentation (P < .01 for both). At 5 years, rates of overall survival, cancer-specific survival, progression-free survival, and distant metastases-free survival in the delayed diagnosis cohort were 80%, 90%, 80%, and 89%, respectively. A >12-month delay in diagnosis did not significantly impact overall survival (adjusted hazard ratio [aHR], 1.16; 95% CI, 0.58-2.31), cancer-specific survival (aHR, 0.83; 95% CI, 0.29-2.39), progression-free survival (aHR, 1.15; 95% CI, 0.56-2.37), or distant metastases-free survival (aHR, 1.00; 95% CI, 0.42-2.40) after adjusting for age, sex, and clinical AJCC stage (P > .05 for all). Delayed diagnosis of HPV(+)OPSCC is associated with greater burden of disease at presentation, but oncologic outcomes remain favorable across treatment modalities. When appropriate, intent-to-cure therapy should be pursued despite diagnostic delay. Level III.

Triplet induction chemotherapy followed by less invasive surgery without reconstruction for human papillomavirus-associated oropharyngeal cancers: Why is it successful or unsuccessful?

De-escalating treatments have been focused on for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). We assessed the efficacy of a triplet induction chemotherapy (ICT) followed by surgery with or without neck dissection (ND) for locally advanced OPSCC, aiming at less invasive surgery without free-flap reconstruction and avoiding postoperative irradiation. This was a retrospective study of 41 patients with advanced resectable HPV-positive OPSCC who underwent ICT followed by surgery of primary resection with or without ND. Patients underwent triplet ICT, including docetaxel, cisplatin, and 5-fluorouracil, or carboplatin, paclitaxel, and cetuximab. Twenty-nine patients had tonsillar cancer, 15 patients were current smokers, and 18 and 12 patients had T2N1M0 and T1N1M0 status (UICC 8th), respectively. After ICT, a surgical procedure without free-flap reconstruction and tracheostomy was possible in 90.2%. Pathological complete response at both the primary site and lymph nodes was achieved in 73.2%. Of the patients who underwent surgery, no adjuvant radiotherapy was required in 85.0%. Two patients (4.9%) experienced recurrence at regional lymph nodes, but were cured by salvage ND followed by adjuvant radiotherapy. Upfront ICT using highly responsive triplet chemotherapeutic regimens may enable us to perform less invasive surgery without free-flap reconstruction and to avoid postoperative irradiation to the locoregional field through excellent postoperative pathological features.

Prospective Evaluation of Swallowing Symptoms in Human Papillomavirus-Associated Oropharynx Cancer.

To demonstrate that the lack of significant swallowing-related symptoms in patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma is attributable to smaller mucosal primaries. A validated dysphagia symptom questionnaire and eating assessment tool was prospectively provided to patients presenting with untreated human papillomavirus-associated oropharyngeal cancer at the University of Maryland from July 2017 to December 2018. A 10-item Eating Assessment Tool (EAT-10) was completed by each patient prior to intervention. All EAT-10 data were collected prospectively. Patient demographic and oncologic characteristics were also obtained. Seventy consecutive patients were enrolled and included in the study. This study cohort included 66 (94%) male patients. Sixty (86%) of patients were Caucasian. The mean EAT-10 score was 3.77 (95% CI 2.04, 5.50). Fifty-two (74.3%) patients presented with normal swallowing (EAT-10 scores less than 3). Spearman correlation indicated there was a significant positive association between tumor size and EAT-10 score (r(68) = 0.429, p < 0.005), with larger tumors associated with increased swallowing-related symptoms. The majority of patients presenting with HPV-associated oropharyngeal squamous cell carcinoma do not report any swallowing difficulties. Dysphagia-related symptoms are associated with large size tumors when they do occur.

The importance of smoking status at diagnosis in human papillomavirus-associated oropharyngeal cancer.

Smoking status at point of diagnosis is not used in defining risk groups for human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) despite its prognostic value in head and neck cancer. Retrospective analysis of consecutive patients treated with chemoradiotherapy between January 2005 and July 2017 was performed with multivariable analysis to explore the impact of smoking status at diagnosis (current/former/never) on overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). Median follow-up was 61 months. Four hundred and four patients were included. Current smokers had inferior OS versus never and former smokers [adjusted HR 2.37 (95% CI 1.26-4.45, p < 0.01) and 2.58 (95% CI 1.40-4.73, p < 0.01), respectively] and inferior PFS versus never smokers [adjusted HR 1.83 (95% CI 1.00-3.35, p = 0.04)]. Smoking status did not predict for CSS. Detailed smoking behavior should be considered in refining risk groups in HPV-associated OPC treated with radiotherapy and in future trial design eligibility and stratification.