HPV-associated Oropharyngeal Squamous Cell Carcinoma Research Articles

Oncological outcomes post transoral robotic surgery (TORS) for HPV-associated oropharyngeal squamous cell carcinoma, a single-centre retrospective Australian study

We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year period. A retrospective case series review was performed of patients undergoing primary surgical treatment for HPV-associated OPSCC through the St. Vincent’s Head and Neck Cancer service from 2011 to 2022. The primary outcomes were to investigate complete resection of the primary tumour, rates of recurrence, and survival analysis. Secondary outcomes included complications, rates of adjuvant therapy, sites of recurrence and rates of percutaneous endoscopic gastrostomy (PEG). 184 patients underwent TORS-based therapy with neck dissection, and guideline-directed adjuvant therapy for HPV-associated OPSCC. Our median follow-up was 46 months. The positive margin rate on final histopathology analysis was 10.9%. Adjuvant therapy was indicated in 85 patients (46%). The local recurrence rate was 10.9% with the majority (80%) of patients recurring in the first 3 years since treatment. The disease-specific survival at 3 years was 98.6% and at 5 years was 94.4%. The 3-year and 5-year OS for the cohort was 96.7% and 92.5%, respectively. The presence of extranodal extension and positive margins were associated with increased risk of recurrence, whereas adjuvant therapy was found to be a protective factor for both overall recurrence and survival. Major complications occurred in 12 patients (6.5%), resulting in one death. This study has demonstrated that primary surgical therapy for HPV-associated OPSCC is a safe and effective treatment modality with low local recurrence and complication rates, and overall survival benefits.

Fibroblasts from HPV-negative oropharynx squamous cell carcinomas stimulate the release of osteopontin from cancer cells via the release of IL-6.

HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) shows distinct biological and clinical behaviour when compared to HPV-negative OPSCC. The overall role of the tumour microenvironment (TME) in head and neck cancer progression and metastasis has been studied intensively, but differences in HPV-negative and HPV-positive OPSCCs are less understood. To investigate the role of cancer-associated fibroblasts (CAFs) and the functional interactions of normal tonsil fibroblasts (NTFs) and OP CAFs with HPV+ and HPV- OPSCC cells and explore novel candidates in tumour-fibroblast crosstalk. A retrospective cohort of 143 primary OPSCCs was characterised using HPV16/18 RNAScope assay, p16 IHC and ɑ-SMA. Four OPSCC, three NTF and 2 new OPSCC CAF cultures were used to assess the cytokine-based interactions using cytokine arrays on conditioned media (CM), followed by co-culture approaches to identify the role of individual cell types and the role of OPN (SPP1) and IL-6 in SCC/fibroblast communication. HPV status was associated with better overall survival. Although ɑ-SMA expression was observed in both OPSCC subtypes, it provided survival stratification only in the HPV-positive group (Log-Rank p = 0.02). Three normal tonsillar fibroblast cultures (NTFs) were characterised by induction of myofibroblastic and senescent phenotypes with similar reactivity to our published NOF phenotype. The OPSCC-derived CAF cultures were characterised and their baseline myofibroblastic and senescence phenotypes varied. Cytokine array analysis of CM to identify novel candidates in the crosstalk between OPSCC tumour cells and NTFs/CAFs identified differences in the cytokine profiles on comparison of HPV+ and HPV- OPSCC cells. Osteopontin (OPN/SPP1) was identified, particularly in HPV-negative OPSCC cell analyses. We have demonstrated that OPN was produced by the OPSCC cells and revealed an associated upregulation of IL-6 in fibroblasts. Treatment of NTFs with rOPN showed alteration in phenotype, including increased contraction and IL-6 production. Antibody-mediated inhibition of CD44v6 attenuated the production of IL-6 by OPN in NTFs. This investigation with OPSCC fibroblasts provides novel insights into the role of CAFs in OPSCC mediated by IL-6 stimulated release of OPN from HPV negative OPSCC cells. The details of HPV-positive SCC cell/fibroblast cytokine crosstalk remain elusive.

Assessing the Knowledge of HPV-Associated Oropharyngeal Squamous Cell Carcinoma, HPV Vaccination, and Practice Scope among Saudi Dental Students in the Western Region.

(1) Background: Human papillomavirus (HPV) infection is significantly associated with oropharyngeal squamous cell carcinoma (HPV-OPSCC), which is one of the fastest-growing cancer incidences globally. Dental practitioners play a crucial role in the primary and secondary prevention of HPV-OPSCC. There is little known about dental students' awareness regarding HPV-OPSCC and HPV vaccination, as well as their intention to promote 'primordial prevention' among their patients. HPV vaccine, and the extent of their professional responsibilities. (2) Methods: This cross-sectional study was conducted in the western region of Saudi Arabia and involved undergraduate dental students (n = 688) from six public and private dental schools. Participants were requested to complete a sequential-section anonymous online survey, with 257 successfully completing all sections of the questionnaire. The association between participant characteristics and HPV-OPSCC, HPV vaccination awareness ratings, and perceived engagement in prevention were analyzed using ANOVA and chi-squared testing. A binary logistic regression analysis was conducted to examine the variables linked to these outcomes. (3) Results: Generally, the overall level of awareness of HPV-OPSCC and HPV vaccination was acceptable, with an average score of 53.44 ± 29.3 out of 100. However, a significant knowledge gap was observed, with 53% of respondents being unaware of the common sites for HPV-OPSCC and 63.8% being uninformed of the appropriate age for HPV vaccination. Females and those with a prior history of sexually transmitted diseases (STDs) had considerably higher levels of HPV vaccination knowledge (p < 0.05). The participants showed a favorable attitude towards their responsibility of informing patients about HPV-OPSCC and advocating HPV immunization. (4) Conclusions: This study underscores the need to enhance dental students' understanding of HPV-OPSCC and HPV immunization, enabling them to effectively engage in primary and secondary preventative efforts against HPV-OPSCC.

P16 overexpression identifies oncogenic high-risk HPV infection in non-oropharyngeal squamous cell carcinoma of the head and neck.

Human papillomavirus (HPV) is an increasing risk factor for cancer. HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favorable outcome. Blockstaining for p16 is a surrogate marker for HPV+ OPSCC. In oral and laryngeal squamous cell carcinoma (OSCC/LSCC), the relevance of p16 immunohistochemistry, alone or in combination with other cell cycle-related proteins, to identify HPV-driven non-OPSCC is less well understood. We stained for p16, pRb, cyclin D1, and p53 in 327 HNSCC. In 310 OPSCC, HPV-status was assessed by HPV DNA PCR. In 119 non-OPSCC, RNA in situ hybridization was additionally performed. HPV-status was correlated with staining patterns, p53 and clinical data. The OPSCC showed blockstaining for p16 in 36%, 8% were equivocal. Of these, HPV-testing was performed in 57%, and 53% were positive for HPV DNA. HPV-association correlated with absence of pRb and cyclin D1 and favorable outcome. In non-OPSCC, 18% showed p16-blockstaining, and 13% showed E6/E7 RNA. Six of seven HPV+ OSCC and 8/8 LSCC lost pRb and cyclin D1. Compared to HPV-negative counterparts, patients with HPV+ cancers had lower rates of alcohol consumption and keratinizing morphology. HPV-positive OSCC had a longer overall survival (p < 0.05). HPV subtype 16 was the most common. We conclude that HPV-positive non-OPSCC are associated with p16 overexpression and low levels of pRb and cyclin D1. High expression of pRb and cyclin D1 indicates HPV-negativity.

Human Papilloma Virus (HPV) driven oropharyngeal cancer in current or previous heavy smokers: should we look for a different treatment paradigm?

Human papillomavirus Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OSCC) has increased in incidence in recent decades and represents a heterogeneous disease entity in the context of Head and Neck Squamous Cell Carcinoma (HNSCC), in terms of disease prognosis. Treatment of locoregionally advanced OSCC is mainly based on concurrent chemoradiotherapy. Given the younger age of patients, if compared with HPV-negative counterparts, and the high cure rates, the acute- and long-term toxicity in survivors represents a field of interest. However, patient selection for de-escalation trials remains a major challenge due to the lack of robust validated prognostic indicators within the HPV-associated OSCC. The impact of smoking status on HPV-associated OSCC prognosis has been demonstrated in the majority of studies. However, the magnitude of the association is unclear due to variability in smoking metrics and study outcomes. Smoking status has been identified as a potential confounding factor in HPV-positive de-escalation trials. Smokers with HPV-positive OSCC have a worse prognosis in most studies than non-smokers and may require different and more aggressive therapeutic strategies.

Utilizing the AJCC 8th Staging to Discriminate Survival Outcomes in HPV-associated Oropharyngeal Squamous Cell Carcinoma.

The American Joint Committee on Cancer (AJCC) staging 8th edition introduced major changes in the TNM staging of oropharyngeal squamous cell carcinoma (OPSCC) based on the human papillomavirus (HPV) status. This study aimed to observe how well the AJCC staging 8th edition precisely discriminates survival outcomes in patients with HPV-associated OPSCC using a large population database. Using the Surveillance, Epidemiology, and End Results database between 2010 and 2016, 7,448 patients with HPV-associated OPSCC were enrolled. Patients diagnosed with OPSCC and tested positive for HPV with information on the TNM staging according to the AJCC staging 7th edition were selected. Next, T-, N-, and clinical staging were reconstructed based on the AJCC staging 8th edition. Survival probabilities in both AJCC staging 7th and 8th editions were estimated and compared. Most patients (93.44%) were down-staged from the 7th to the 8th edition. The AJCC staging 8th edition showed more discriminatory power in predicting survival of patients with HPV-associated OPSCC than the AJCC staging 7th edition, regardless of the primary subsites. Additionally, clinical stage I patients with HPV-associated OPSCC according to the AJCC 8th edition showed better prognosis in case of high T staging than high N staging. Clinical staging according to the AJCC 8th edition compared to that of the 7th edition was an independent prognostic factor in patients with HPV-associated OPSCC. This study emphasizes the advantages of the new classification system for discriminating survival in HPV-associated OPSCC according to various factors.

Abstract 7661: Integrating radiomic features from primary tumor and lymph node for survival prediction of HPV-associated oropharyngeal squamous cell carcinoma

Abstract Background: HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) is a unique disease with improved prognosis which could benefit from treatment de-escalation. Current radiographic-based biomarkers mainly focus on primary tumor (PT) alone, neglecting the potential prognostic value from the lymph node (LN). In this work, we constructed a radiomic model integrating texture features from both PT and LN to predict overall survival (OS) in HPV-associated OPSCC patients. Methods: Pretreatment CT scans for 647 OPSCC patients treated with definitive radiation with or without chemotherapy were acquired from The Cancer Imaging Archive (TCIA) and the Cleveland Clinic (CCF), which were divided into training set D1 (n=294) and test set D2 (n=353). PT and LN contours were annotated by three. 2045 texture radiomic features were extracted from both PT and LN and were concatenated as input to a LASSO Cox model to predict OS. We used the harrell’s concordance index (C-index) and hazard ratio (HR) to evaluate the prognostic performance. We also performed the multivariable cox proportional hazard analysis adjusting for clinicopathological variables to validate the independent prognostic significance. Results: Among the 647 patients, median follow-up time was 70.23 months, with 155 patients (24%) experienced death. 22.6%, 38.8%, 23.2% and 15.4% had T stage I, II, III and IV tumors, respectively. 203 patients (31.4%) were treated with radiation alone. The model integrating PT and LN (M_PTLN) yielded higher C-index compared to PT alone (M_PT) on D1 (0.74 vs 0.66) and on D2 (0.64 vs 0.61). In univariate analysis on D2, M_PTLN is prognostic of OS (HR, 2.26; 95% CI, 1.32 - 3.87; log rank p = 0.003). In multivariable analysis, M_PTLN is still statistically significant (p = 0.04) accounting for clinicopathologic factors (age, gender, smoking pack-year [PY], T stage, N stage and treatment modality). Conclusions: We developed and validated a CT-based survival prediction model for HPV-associated OPSCC patients with significant prognostic values, accounting for both primary tumor and lymph node. If prospectively validated, the model has the potential to inform trial eligibility and treatment-related decision making. Citation Format: Bolin Song, Amaury Leroy, Kailin Yang, Qiyun Liu, Xiao Li, Jonathan Lee, Sarah Stock, Nabil F. Saba, James S. Lewis, Eric Deutsch, Mehmet Asim Bilen, Shlomo A. Koyfman, Anant Madabhushi. Integrating radiomic features from primary tumor and lymph node for survival prediction of HPV-associated oropharyngeal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7661.

Abstract 1025: An AI based CT scan classifier for predicting extranodal extension and nodal metastasis of HPV-associated oropharyngeal carcinoma

Abstract Background: Pathologic extranodal extension (ENE) and nodal metastasis (NM) are of prognostic significance in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). The pretreatment identifications of these two factors through computed tomography (CT) imaging are of clinical importance since they could guide treatment de-escalation protocols and select candidates suitable for surgery. In an effort to enhance pretreatment decision making, we developed and validated an AI model (specifically a multi-layer perceptron (MLP)-based deep learning model) to predict radiologic NM and pathologic ENE in HPV-associated OPSCC patients. Methods: Radiographic CT scans for 290 OPSCC patients treated with definitive chemoradiation were acquired from The Cancer Imaging Archive (TCIA) and divided into training (D1) and validation (D2) cohorts for NM prediction. Radiologic NM for D1 and D2 were reviewed by two radiologists. Only nodes with concordant NM judgments from both radiologists were included for analysis. An additional 46 OPSCC patients treated with surgery at Emory Winship Cancer Institute were collected to form the test cohorts (D3) for ENE prediction. The largest metastatic or normal nodes were annotated for D1 and D2 while all visible nodes with pathology confirmation of ENE from D3 were annotated. We present a novel deep-learning model utilizing U-shaped multi-layer perceptron mixer (MLP-Mixer) to capture both global and local feature representations by spatially aggregating image patch information through a procedure called token-mixing. The model was trained for 20 epochs with learning rate of0.0001 and batch size of 64. The diagnostic performance of the AI model was evaluated on D2 and D3 using accuracy and area under the ROC curve (AUROC). Results: There were 121 NM negative and 130 NM positive nodes in D1, 14 NM negative and 25 NM positive nodes in D2 and 46 ENE negative and 20 ENE positive nodes in D3. On D2 for NM prediction, the AI model achieved overall accuracy of 0.77 and AUROC of 0.78. On D3 for ENE prediction, the AI model achieved overall accuracy of 0.71, AUROC of 0.69, positive predictive value of 0.52 and negative predictive value of 0.86. Conclusions: The new AI–based deep learning model was able to identify HPV-associated OPSCC NM and ENE with satisfactory diagnostic performance and shows promise to assist clinicians in treatment decision-making. Additional, multi-site prospective validation of the approach is warranted. Citation Format: Bolin Song, Kailin Yang, Shaoyan Pan, Liping Li, Qiyun Liu, Jonathan Lee, Sarah Stock, Nabil F. Saba, Mehmet Asim Bilen, Mihir R. Patel, Anant Madabhushi. An AI based CT scan classifier for predicting extranodal extension and nodal metastasis of HPV-associated oropharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1025.

Atypical Regional Metastasis to the Parotid Nodal Basin in HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

Atypical Regional Metastasis to the Parotid Nodal Basin in HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

Improving HPV-Related Oropharyngeal Cancer Knowledge and HPV Vaccination Rates via Virtual Workshops.

To validate the efficacy of a virtual, interdisciplinary workshop in improving HPV knowledge, and vaccination practices among primary care and dental trainees. A virtual platform was utilized to hold HPV educational workshops with primary care and dental trainees. Online surveys were distributed before and after the 1-h interactive workshop, led by otolaryngology residents. Surveys included the workshop's impact on (a) improving knowledge of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and (b) affecting change in HPV vaccination practices. The vaccination rates of trainees were recorded prior to and after workshop attendance. After the workshop, participants demonstrated significantly improved scores related to knowledge of HPV in the head and neck (p = 0.003) and showed an increased comfort level with counseling on HPV vaccination (p = 0.002). Respondents were also more aware that the HPV vaccine is approved to prevent OPSCC (61% vs. 95%, p < 0.05). Ninety-seven percent of respondents stated that the workshop changed their HPV vaccination practices, and 95% of those not fully vaccinated stated they would now be more likely to receive the vaccine themselves. There was a significant increase in the average number of HPV vaccines administered at the studied trainee clinic, from 16.83 vaccines/month to 37.6 vaccines/month (percent increase = 123%) in 5 months following the workshop (p = 0.002). The present interactive virtual workshop demonstrates efficacy in improving HPV-related knowledge and vaccination practices among trainees. The virtual nature of the course facilitates knowledge transfer and can be used to foster multi-institutional partnerships regarding medical education and vaccination efforts. 4 Laryngoscope, 134:3096-3101, 2024.

Assessing the feasibility of a multimodal liquid biopsy for the diagnosis of HPV-associated oropharyngeal squamous cell carcinoma.

In this feasibility study, we explored the combined use of circulating tumor human papillomavirus (HPV) DNA (ctHPVDNA) and HPV serology as diagnostic tests for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Among patients with research-banked serum or plasma at diagnosis, IgG antibodies to oncoproteins from HPV types 16, 18, 31, 33, 35, 45, 52, and 58 were detected with multiplex serology. Positivity for HPV 16 was defined based on detection of combinations of anti-E6, E1, E2, and E7 and for other high-risk types on detection of anti-E6 and anti-E7. Circulating tumor HPV DNA was detected by custom digital droplet polymerase chain reaction (ddPCR) assays for HPV types 16, 18, 33, 35, and 45. p16 immunohistochemistry and high-risk HPV RNA in situ hybridization (ISH) using a cocktail of 18 high-risk HPV types were performed on tissue. Of 75 patients, 67 (89.3%) were HPV-associated (p16 and HPV RNA ISH positive) and 8 (10.7%) were HPV-independent. All 8 HPV-independent patients were seronegative and negative for ctHPVDNA (100% specificity). Serology was positive in 53 (79.1%) of 67 HPV-associated patients, while ddPCR was positive for ctHPVDNA in 59 (88.6%) of 67 HPV-associated patients. Requiring both tests to be positive resulted in a sensitivity of 50 (74.6%) of 67 while combining assays (either positive) improved sensitivity to 62 (92.6%) of 67. Compared to HPV RNA ISH, HPV serology and ctHPVDNA are sensitive and highly specific biomarkers for HPV-associated OPSCC at the time of presentation.

CtDNA transiting into urine is ultrashort and facilitates noninvasive liquid biopsy of HPV+ oropharyngeal cancer.

BACKGROUNDTransrenal cell-free tumor DNA (TR-ctDNA), which transits from the bloodstream into urine, has the potential to enable noninvasive cancer detection for a wide variety of nonurologic cancer types.MethodsUsing whole-genome sequencing, we discovered that urine TR-ctDNA fragments across multiple cancer types are predominantly ultrashort (<50 bp) and, therefore, likely to be missed by conventional ctDNA assays. We developed an ultrashort droplet digital PCR assay to detect TR-ctDNA originating from HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) and confirmed that assaying ultrashort DNA is critical for sensitive cancer detection from urine samples.ResultsTR-ctDNA was concordant with plasma ctDNA for cancer detection in patients with HPV+ OPSCC. As proof of concept for using urine TR-ctDNA for posttreatment surveillance, in a small longitudinal case series, TR-ctDNA showed promise for noninvasive detection of recurrence of HPV+ OPSCC.ConclusionOur data indicate that focusing on ultrashort fragments of TR-ctDNA will be important for realizing the full potential of urine-based cancer diagnostics. This has implications for urine-based detection of a wide variety of cancer types and for facilitating access to care through at-home specimen collections.FundingNIH grants R33 CA229023, R21 CA225493; NIH/National Cancer Institute grants U01 CA183848, R01 CA184153, and P30CA046592; American Cancer Society RSG-18-062-01-TBG; American Cancer Society Mission Boost grant MBGI-22-056-01-MBG; and the A. Alfred Taubman Medical Research Institute.

Unveiling Liquid Gold: Lymph as an HPV Marker in OPSCC to Guide Treatment Decisions.

Distinguishing low- versus high-risk HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) is pivotal for tailoring treatment. Liquid biopsy, measuring cell-free HPV-DNA in serum and saliva, assesses treatment response and early-recurrence risk. Postoperative lymphatic fluid may better guide future adjuvant therapy decisions due to its proximity to primary lesions and lymph nodes. See related article by Earland et al., p. 1409.

A Descriptive Study of Quality of Life Following Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with radiation-based therapy suffer from short- and long-term toxicities that affect quality of life (QOL). Transoral robotic surgery (TORS) has an established role in the management of early OPSCC but adjuvant treatment is often indicated postoperatively due to the high incidence of nodal metastasis associated with advanced human papillomavirus (HPV)-related OPSCC. To overcome the need for adjuvant radiation therapy (RT), neoadjuvant chemotherapy followed by TORS and neck dissection (ND) is proposed. This study aimed to assess if QOL in HPV-associated OPSCC receiving neoadjuvant chemotherapy followed by TORS and ND returns to baseline within 12 months of completing treatment. A 12 month longitudinal study was carried out at McGill University Health Centre in Montreal, Canada, among a convenience sample of patients with American Joint Committee on Cancer Seventh Edition stage III and IVa HPV-related OPSCC who were treated with neoadjuvant chemotherapy followed by TORS and ND. QOL data were obtained pretreatment and at 1, 3, 6, and 12 months following treatment completion using the European Organisation for Research and Treatment of Cancer Core and Head and Neck extension modules. Paired t tests and mixed models for repeated measures analysis were used to assess changes in QOL from baseline to 12 months postoperatively and over time, respectively. Nineteen of 23 patients (median age 58 years) who received the study treatment fulfilled the eligibility criteria. OPSCC subsites were palatine tonsil (n = 12) and base of tongue (n = 7). All 19 patients were treated per protocol and none required adjuvant RT as per pathology review and protocol requirements at a postoperative multidisciplinary team tumor board discussion. No significant differences were found when comparing 12 month QOL follow-up scores to pretreatment scores in measures that would likely be affected by RT [eg, swallowing (P = .7), social eating (P = .8), xerostomia (P = .9)]. In HPV-related OPSCC, neoadjuvant chemotherapy followed by TORS and ND as definitive treatment is associated with excellent QOL outcomes. Postoperative QOL scores returned to baseline by 3 months and were maintained for all measures, indicating a return to normal function.

A single-centre UK service evaluation and comparison of outcomes of radically treated HPV-associated oropharyngeal squamous cell carcinoma before and during the COVID-19 pandemic

A single-centre UK service evaluation and comparison of outcomes of radically treated HPV-associated oropharyngeal squamous cell carcinoma before and during the COVID-19 pandemic

Findings from a Malaysian multicentre study on oropharyngeal squamous cell carcinoma

BackgroundIn addition to the conventional aetiologic agents of oropharyngeal squamous cell carcinoma (OPSCC) such as tobacco usage, alcohol consumption and betel quid usage, it has been established that a proportion of OPSCC are driven by persistent oncogenic human papillomavirus (HPV) infections. Currently, there is a lack of data on the burden of HPV- associated OPSCC in Asian countries including Malaysia.MethodsA cross-sectional multicentre study with tissue analysis of Malaysian patients diagnosed with primary OPSCC within a five-year period, from 2015 to 2019 between 01/01/2015 to 31/12/2019 was undertaken. Determination of HPV status was carried out using p16INK4a immunohistochemistry on tissue microarrays constructed from archived formalin-fixed paraffin-embedded tissue.ResultsFrom the cases identified, 184 cases had sufficient tissue material for analysis. Overall, median age at diagnosis was 63.0 years (IQR = 15) and 76.1% of patients were males. In our cohort, 35.3% of patients were Indian, 34.2% were Chinese, 21.2% were Malay and 9.2% were from other ethnicities. The estimated prevalence of HPV-associated OPSCC in our cohort was 31.0% (CI 24.4–38.2%). The median age for the HPV-associated OPSCC sub-group of patients was not significantly lower than the median age of patients with HPV-independent OPSCC. More than half of HPV-associated OPSCC was seen in patients of Chinese ethnicity (54.4%). Patients with HPV-associated OPSCC had a much better overall survival than patients with HPV-independent OPSCC (Log rank test; p < 0.001). Patients with HPV-associated OPSCC with no habit-related risk factors such as smoking, were found to have much better overall survival when compared to all other sub-groups.ConclusionsThe findings from our study suggests that prevalence of HPV-associated OPSCC in Malaysia, though not as high as some developed countries, is however on an upward trend. HPV-associated OPSCC appears to be more frequently encountered in patients of Chinese ethnicity. Conventional risk-factors associated with OPSCC such as smoking, alcohol consumption and betel quid chewing should still be considered when estimating prognosis of patients with HPV-associated OPSCC.

Clinical outcomes of oropharyngeal squamous cell carcinoma stratified by human papillomavirus subtype: A systematic review and meta-analysis

PurposeWe aim to determine if there is a survival difference between patients with oropharyngeal squamous cell carcinoma (OPSCC) associated with human papillomavirus (HPV) 16 versus HPV-non16 subtypes. Patient and methodsDatabases were queried for full length, peer-reviewed, English language, articles published between 01/01/1980 and 06/08/2022. Studies reporting clinical outcomes of OPSCC associated with HPV16 and HPV-non16 subtypes with at least 10 patients were included. Primary outcome was the overall survival (OS) of patients with HPV16- versus HPV-non16-associated OPSCC. Secondary outcomes were recurrence-free survival (RFS) and pooled rate of p16 positivity by immunohistochemistry (IHC). ResultsA total of 9 studies met inclusion criteria and included 1,310 patients with HPV16 and 219 with HPV-non16 subtypes of OPSCC. The prevalence of HPV-non16 was 14.3 %. The pooled 5-year OS rates for patients with HPV16 and HPV-non16 were 83.4 %(95 % CI 77.8–89.0 %) and 69.3 %(95 % CI 58.5–80.1 %), respectively. OS at 5 years was significantly worse for HPV-non16 subtype, compared to HPV16 (log odds ratio [OR] −0.54, p = 0.008). There was a trend towards worse 5-year RFS with HPV-non16 compared to HPV16 (log OR −0.55, p = 0.063). Patients with HPV-non16 disease were less likely to be p16 positive by IHC (log OR −0.91, p = 0.02). ConclusionPatients with HPV-non16OPSCC may experience worse OS and were less likely to be p16 positive compared to patients with HPV16 disease. While future prospective validation is warranted, routine assessment of both p16 IHC and HPV subtype could be considered prior to pursuing treatment de-escalation for HPV-associated OPSCC.

NTCP modelling of xerostomia after radiotherapy for oropharyngeal cancer using the PRO-CTCAE and CTCAE scoring systems at different time-points post-RT

PurposeThis study aims at determining the parameter values of three normal tissue complication probability (NTCP) models for the contralateral parotid gland, contralateral submandibular gland (SMG) and contralateral salivary glands regarding the endpoint of xerostomia 6–24 months after radiotherapy for oropharynx cancer. MethodsThe treatment and outcome data of 231 patients with favorable risk, HPV-associated oropharyngeal squamous cell carcinoma are analyzed. 60 Gy intensity modulated radiotherapy was delivered to all the patients. The presence and severity of xerostomia was recorded (pre- and post- radiotherapy) by the PRO-CTCAE and the CTCAE scoring systems. In both scoring systems, patients with a change in symptom severity (from baseline) of ≥ 2 were considered responders. ResultsXerostomia was observed in 61.3 %, 39.2 %, 28.6 % and 27.0 % of the patients based on the PRO-CTCAE scoring system at 6-, 12-, 18- and 24-months post-RT, respectively. The AUCs of the contralateral salivary glands ranged between 0.58–0.64 in the LKB model with the gEUD ranging between 20.3 Gy and 24.7 Gy. ConclusionsBased on the PRO-CTCAE scores, mean dose < 22 Gy, V50 < 10 % for the contralateral salivary glands and mean dose < 18 Gy, V45 < 10 % for the contralateral parotid were found to significantly reduce by a factor of 2–3 the risk for radiation induced xerostomia that is observed at 6–24 months post-RT, respectively. Also, gEUD < 22 Gy to the contralateral salivary glands and < 18 Gy to the contralateral parotid was found to significantly reduce the risk for radiation induced xerostomia that is observed at 6–24 months post-RT by 2.0–2.3 times.

Robotic surgery in the treatment of oropharyngeal cancer: a case report

Background. The incidence of HpV-associated oropharyngeal squamous cell carcinoma (oscc) is steadily increasing. given the better prognosis in patients with HpV-positive cancer compared to HpV-negative cancer, attempts were made to reduce the therapeutic effect in patients with early-stage oscc to improve the quality of life of these patients. early-stage oscc can currently been treated with radiation therapy or surgery used alone or in combination. Currently, the concept of transoral surgery includes both transoral laser microsurgery and robot-assisted surgeries (da Vinci, medrobotics Flex system). Case description. We report a case of using the da Vinci robot-assisted system in the combined modality treatment of oropharyngeal cancer. The patient underwent surgery followed by chemoradiotherapy. At a follow-up of 10 months, no evidence of disease progression was found. The patient experienced no any pain on swallowing.Conclusion. The use of the da Vinci robot-assisted surgical system in the combined modality treatment of oropharyngeal cancer, especially in such a hard-to-reach area as the root of the tongue, makes it possible to better visualize and determine the boundaries of the lesion, followed by en block resection, as well as to improve functional and aesthetic results. However, careful selection of patients for this type of treatment is necessary.

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.