Immunological dynamics in orthotopic compared with subcutaneous murine models of HPV-positive oropharyngeal cancer

Oropharyngeal squamous cell carcinoma (OPSCC) is associated with human papillomavirus (HPV) in a proportion of tumors. HPV-positive OPSCC is considered a distinct molecular entity with a prognostic advantage compared to HPV-negative cases. Silencing of cancer-related genes by DNA promoter hypermethylation may play an important role in the development of OPSCC. Hence, we examined promoter methylation status in 24 common tumor suppressor genes in a group of 200 OPSCCs to determine differentially methylated genes in HPV-positive versus HPV-negative primary OPSCC. Methylation status was correlated with HPV status, clinical features, and patient survival using multivariate methods. Additionally, methylation status of 16 cervical squamous cell carcinomas (SCC) was compared with HPV-positive OPSCC. Using methylation-specific probe amplification, HPV-positive OPSCC showed a significantly higher cumulative methylation index (CMI) compared to HPV-negative OPSCC (P=0.008). For the genes CDH13, DAPK1, and RARB, both HPV-positive and HPV-negative OPSCC showed promoter hypermethylation in at least 20% of the tumors. HPV status was found to be an independent predictor of promoter hypermethylation of CADM1 (P < 0.001), CHFR (P = 0.027), and TIMP3 (P < 0.001). CADM1 and CHFR showed similar methylation patterns in OPSCC and cervical SCC, but TIMP3 showed no methylation in cervical SCC in contrast to OPSCC. Methylation status of neither individual gene nor CMI was associated with survival. These results suggest that HPV-positive tumors are to a greater extent driven by promotor hypermethylation in these tumor suppressor genes. Especially CADM1 and TIMP3 are significantly more frequently hypermethylated in HPV-positive OPSCC and CHFR in HPV-negative tumors.

Growing evidence suggests that as many as half of all oropharyngeal squamous cell carcinomas (OPSCCs) harbor human papillomavirus (HPV) infections. Despite being more advanced at diagnosis, HPV-positive OPSCCs are associated with a better response to therapy and longer patient survival than HPV-negative OPSCCs. Human papillomavirus-positive OPSCC has also been shown to have distinct host gene expression profiles compared with HPV-negative OPSCC. Recently, this distinction has been shown to include the epigenome. It is well supported that cancers are epigenetically deregulated. This review highlights epigenetic differences between HPV-positive and HPV-negative OPSCCs. The epigenetic mechanisms highlighted include methylation changes to host and viral DNA, and host chromatin modification. We also review the current evidence regarding host DNA methylation changes associated with smoking, and deregulation of microRNA expression in HPV-positive OPSCC. To provide an overview of epigenetic mechanisms reported in HPV-positive OPSCC, with analogies to cervical cancer, and discussion of the challenges involved in studying epigenetic changes in HPV-associated OPSCC in combination with changes associated with smoking. Sources were a literature review of peer-reviewed articles in PubMed on HPV and either OPSCC or head and neck squamous cell carcinoma, and related epigenetic mechanisms. Epigenetic changes are reported to be a contributing factor to maintaining a malignant phenotype in HPV-positive OPSCC. The epigenetic mechanisms highlighted in this review can be studied for potential as biomarkers or as drug targets. Furthermore, continued research on the deregulation of epigenetic mechanisms in HPV-positive OPSCC (compared with HPV-negative OPSCC) may contribute to our understanding of the clinical and biologic differences between HPV-positive and HPV-negative OPSCC.

ObjectivesPatients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs) have an improved prognosis compared to HPV-negative OPSCCs. Several theories have been proposed to explain this relatively good prognosis. One hypothesis is a difference in immune response. In this study, we compared tumor-infiltrating CD3+, CD4+, CD8+ T-cells, and granzyme inhibitors (SERPINB1, SERPINB4, and SERPINB9) between HPV-positive and HPV-negative tumors and the relation with survival.MethodsProtein expression of tumor-infiltrating lymphocytes (TILs) (CD3, CD4, and CD8) and granzyme inhibitors was analyzed in 262 OPSCCs by immunohistochemistry (IHC). Most patients (67 %) received primary radiotherapy with or without chemotherapy. Cox regression analysis was carried out to compare overall survival (OS) of patients with low and high TIL infiltration and expression of granzyme inhibitors.ResultsHPV-positive OPSCCs were significantly more heavily infiltrated by TILs (p < 0.001) compared to HPV-negative OPSCCs. A high level of CD3+ TILs was correlated with a favorable outcome in the total cohort and in HPV-positive OPSCCs, while it reached no significance in HPV-negative OPSCCs. There was expression of all three granzyme inhibitors in OPSCCs. No differences in expression were found between HPV-positive and HPV-negative OPSCCs. Within the group of HPV-positive tumors, a high expression of SERPINB1 was associated with a significantly worse overall survival.ConclusionHPV-positive OPSCCs with a low count of CD3+ TILs or high expression of SERPINB1 have a worse OS, comparable with HPV-negative OPSCCs. This suggests that the immune system plays an important role in the carcinogenesis of the virally induced oropharynx tumors.

Survival for HPV-positive oropharyngeal squamous cell carcinoma with surgical versus non-surgical treatment approach: A systematic review and meta-analysis

Human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC) are distinct disease entities. Prognostic factors specific to each entity have not been adequately explored. Goals for this study were: 1) to determine whether HPV-positive and HPV-negative OPSCCs have distinct prognostic factors, and 2) to explore the prognostic significance of sex and race in OPSCC after HPV stratification STUDY DESIGN: Retrospective case series. A retrospective review of 239 incident OPSCC patients from 1995 to 2012, treated at Johns Hopkins and University of California-San Francisco was conducted. Women and nonwhite races were oversampled. All analyses were stratified by tumor HPV in situ hybridization status. The effects of sex and race on survival were considered in Kaplan-Meier and unadjusted and adjusted Cox regression models. One hundred thirty-four (56.1%) OPSCC patients were HPV positive. On univariate analysis, women had better overall survival than men among HPV-positive (hazard ratio [HR]: 0.47, 95% confidence interval [CI]: 0.20-1.07; P = .06) but not HPV-negative (HR: 0.73, 95% CI: 0.43-1.24; P = .24) OPSCCs. On multivariate analysis, women with HPV-positive OPSCCs remained at lower risk of death (adjusted hazard ratio [aHR]: 0.34, 95% CI: 0.12-0.96; P = .04). Survival did not vary significantly by race among HPV-positive patients. Among HPV-negative patients, Hispanic patients had significantly better survival in unadjusted (HR: 0.27, 95% CI: 0.08-0.91; P = .04) but not adjusted (aHR: 0.93, 95% CI: 0.11-7.36; P = .94) analysis. Women with HPV-positive OPSCC may have improved overall survival compared to men. Sex does not play a prognostic role in HPV-negative OPSCC. There are no differences in prognosis by race among HPV-positive or HPV-negative patients. 4 Laryngoscope, E287-E295, 2018.

Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis than patients with HPV-negative OPSCCs. Important factors contributing to this better prognosis are relatively low numbers of local/regional recurrences (LRRs) and second primary tumors (SPTs) in patients with HPV-positive OPSCC. These low numbers may be explained in addition by the absence of a 'field cancerization' effect, which is a cause of LRRs and SPTs in patients with HPV-negative OPSCC. We aimed to detect a possible 'field effect' in patients with HPV-positive OPSCC. As HPV is involved in the early stage of carcinogenesis in OPSCCs, its presence is considered a reliable marker for the detection of such a field effect. Therefore, the presence of transcriptionally active HPV was analyzed in the mucosa surrounding HPV-positive OPSCCs. We included 20 patients who were surgically treated for an HPV-positive OPSCC in the period 2000-2006. Of each patient, the formalin-fixed paraffin-embedded tumor sample and all available resection margins were collected. In total, 97 resection margins were investigated with an average of five resection margins per tumor. All samples were analyzed for the presence of tumor and the presence of transcriptionally active HPV by HPV16-E6-mRNA detection. All tumors were HPV16-E6-mRNA positive. HPV16-E6-mRNA could be detected in the resection margins that contained tumor (n = 6). All tumor-negative resection margins (n = 91) scored negative for HPV16-E6-mRNA. In conclusion, transcriptional active HPV could not be detected in the mucosa surrounding an HPV-positive OPSCC, which suggests the absence of field effect. This observation may explain the lower number of LRRs and SPTs in HPV-positive patients.

In spite of decreases in the incidence of smoking in the United States over the past several decades, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing. This is presumably due to an increase in the incidence of human papillomavirus (HPV)-positive OPSCC. The model for how HPV contributes to cancer development is based upon studies characterizing cervical cancer. In cervical cancer almost all invasive cancers have HPV integrated into the human genome with loss of episomal copies of HPV. The site of integration is usually within the HPV E2 gene which functions as a repressor of the two key HPV oncoproteins, E6 and E7. The resulting over-production of E6 and E7 inactivates two key pathways which results in genomic instability and additional down-stream alterations that eventually leads to invasive cervical cancer. In order to definitively test whether this model is indeed true for OPSCC we performed mate-pair next generation sequencing on both tumor and adjacent normal tissues from 20 OPSCC patients: 7 were HPV16-positive and had high expression of the E6 and E7 transcripts; 6 were HPV-positive but with low E6 and E7 transcription; and as a control we also analyzed 7 HPV16-negative tumors. This high throughput technology was able to successfully detect all HPV integration events into the human genome as well as HPV bridged coverage from these samples with high specificity. Just a single HPV-positive tumor with high oncogene expression had HPV integration events (two), but this patient also had a very high copy number of episomal HPV sequences. A single HPV-positive tumor with low oncogene expression had one HPV integration event, but no episomal HPV sequences present. One of the HPV16-negative tumors had a single HPV26 integration with no episomal HPV sequences. None of the matched normal samples had either HPV integrations or an appreciable amount of episomal HPV sequences present. Thus, only 21.4% of HPV-positive OPSCCs had integrations event. All four integrations were validated by PCR and Sanger sequencing which revealed that none of them interrupted the HPV E2 gene. All four of the integrations occurred next to human genes that have been found to be altered in different cancers. Our results suggest that the role that HPV plays in OPSCC may be quite distinct from what is observed in cervical cancer. The results also demonstrate that not all HPV-positive OPSCCs have HPV in the same physical state. It will thus be interesting to compare the distinct groups of HPV-positive OPSCCs with respect to overall clinical prognosis. Citation Format: Ge Gao. Mate pair sequencing reveals that human papillomavirus integration into the human genome in oropharyngeal squamous cell carcinoma is rare and different from cervical cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4147. doi:10.1158/1538-7445.AM2014-4147

Background: The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased in recent years. HPV-associated OPSCC follows a distinct carcinogenic pathway from HPV-negative OPSCC. The molecular basis of the disease progression due to HPV remains to be elucidated. Clinical observations have revealed frequent and early lymph node metastasis and unusual distant metastasis in HPV-associated as compared with HPV-negative OPSCC. To understand the underlying molecular mechanism, we have studied whether β-catenin, one of the major proteins in the Wnt pathway, is involved in HPV-associated OPSCC metastasis. Methods: The study samples (n = 210) were collected from formalin-fixed and paraffin-embedded OPSCC tissues obtained from the Surgical Pathology files in the Department of Pathology at Emory University following the regulations of the Health Insurance Portability and Accountability Act (HIPAA). Expression levels of p16 as a surrogate marker for HPV-associated cancer, β-catenin, and epidermal growth factor receptor (EGFR) were determined by immunohistochemistry (IHC) analyses. Membrane expression of β-catenin and total EGFR level were scored as a weight index [WI = intensity (0, 1+, 2+, and 3+) x % of positive staining]. Nuclear β-catenin and p16 were recorded as positive and negative. Expression and subcellular localization of β-catenin as well as EGFR expression and activation were also studied in both HPV-positive and -negative head and neck SCC (HNSCC) cell lines (n =7) by Western blot analysis. SiRNA against HPV E6 was used to elucidate the effect of HPV on β-catenin translocation. Results: Our results showed that membrane WI of β-catenin was inversely correlated with p16 positivity (p &amp;lt; 0.0001), while nuclear staining of β-catenin was associated with p16 positive OPSCC (p = 0.007) and positive lymph nodes (p = 0.0304). A low level of membrane β-catenin (cut-off by the median value) was significantly associated with disease free survival and overall survival (p &amp;lt; 0.05 in both cases). Furthermore, WI EGFR was positively correlated with nuclear β-catenin (p = 0.0001). Our in vitro study showed that nuclear β-catenin level was higher in HPV16-positive HNSCC cell lines than in HPV16-negative cell lines. Furthermore, HPV16-positive cells showed higher EGFR activation than HPV16-negative cells. Reduction of HPV16 E6 led to the de-activation of EGFR and decreased level of β-catenin in the nucleus. Conclusion: Our findings suggest that HPV16 E6 mediates the translocation of β-catenin to the nucleus, which may be regulated by activated EGFR. The underlying mechanism deserves further investigation. (This study was supported by US National Institutes of Health (NIH/NCI) grant HHSN2610201000125C, R33 CA134392-01, and Georgia Cancer Coalition Distinguished Cancer Scholar Award to ZGC). Citation Format: Zhongliang Hu, Ning Jiang, Susan Muller, Nabil Saba, Dongsheng Wang, Hongzheng Zhang, Dong M. Shin, Zhuo Georgia Chen. Subcellular translocation of β-catenin and its relationship with EGFR activation in HPV16 positive OPSCC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4798. doi:10.1158/1538-7445.AM2013-4798

Sexual behavior is associated with human papillomavirus (HPV)-positive head and neck cancer, whereas tobacco and alcohol use are associated with HPV-negative cancer. A case-control study was designed to investigate additional demographic and behavioral factors independently associated with these distinct oral cancers. From 2011 to 2014, 249 newly diagnosed oral cavity and oropharyngeal squamous cell carcinoma (OSCC) cases were matched (1:2) on age, gender, and self-identified race to 498 controls without a cancer history attending the outpatient otolaryngology clinic at The Ohio State University in Columbus. Cases were stratified by detection of high-risk HPV DNA and RNA in tumors. Demographic and behavioral data were collected using an audio computer-assisted self-interview, and associations with HPV-positive versus HPV-negative OSCCs were investigated by use of univariable and multivariable conditional logistic regression models. After adjustment for oral sexual behavior, the odds of HPV-positive cancer decreased with the patient's years of education. Annual income, tobacco smoking, alcohol drinking, marijuana smoking, and poor oral hygiene were not associated with HPV-positive OSCC. In contrast, the odds of HPV-negative OSCC increased independently with decreased annual income, decreased with a high number of marijuana hit-years, and increased with fewer than annual dental visits after adjustment for lifetime tobacco and alcohol use. Sexual behavior and education were not associated with HPV-negative OSCC. The distinct risk-factor profiles for HPV-positive and HPV-negative OSCC are confirmed and extended in this case-control study, thus supporting 2 principal etiological pathways for OSCC development. Sexually acquired human papillomavirus (HPV) infection is an established cause of tonsil and base of tongue cancers. This study compared and contrasted risk factors for HPV-positive and HPV-negative oral cancers. Low number of years of education and sexual behavior are associated with HPV-positive cancer. In contrast, low annual income, infrequent dental visits, and tobacco and alcohol use are associated with HPV-negative cancers. Long-term marijuana use appears protective for HPV-negative cancer. Public health efforts to address these modifiable risk factors may prevent oral cancer.

THE PREVALENCE OF HPV POSITIVE OROPHARYNGEAL SQUAMOUS CELL CARCINOMA AT A MAJOR REFERRAL CENTER IN SOUTHERN AFRICA

Studies have found that, at presentation, human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has a less advanced primary tumour, more advanced lymph node spread and commonly has cystic metastatic lymph nodes in comparison to HPV-negative OPSCC. To compare the radiological features of HPV-positive and HPV-negative OPSCC in South African patients. A retrospective cross-sectional study was conducted at a large South African hospital. Eligibility required a histologically proven OPSCC between 2007 and 2023; a p16 antigen test and, if positive, a confirmatory HPV DNA PCR test and a baseline pre-treatment contrast enhanced neck CT scan. All eligible HPV-positive OPSCC patients and a random sample of eligible HPV-negative OPSCC patients were enrolled. Twenty-one HPV-positive and 55 HPV-negative OPSCC patients were recruited. There was no statistically significant difference in the tumour epicentre location, local advancement (≥ T3 in 67% and 71%, respectively, p = 0.54), mean primary tumour size (41 mm vs. 39 mm, p = 0.73), lymph node spread (bilateral or more in 67% vs. 82%, p = 0.22) or morphologically cystic lymph nodes (10% and 4%, p = 0.61). There was no statistically significant difference in the CT imaging appearances of HPV-positive and HPV-negative OPSCC in the studied sample of South African patients. This study documents the radiological features of OPSCC in a small South African sample population, where HPV-positive and HPV-negative OPSCC could not be distinguished on CT criteria and did not display the classic features described in the literature.

10591 Background: HPV-positive and negative OSCC, despite a common EGFR expression, have a distinct biology and clinical behaviour, thus we hypothesize different mechanisms of primary resistance to EGFRi. Methods: PI3KCA, PTEN, HER2 and IGF-1R status was investigated in 17 HPV16-positive and 57 HPV16-negative fixed untreated OSCCs through FISH, sequencing, cDNA relative quantification by means of real-time PCR (method 2-ΔΔCt) and immunohistochemistry. Results: PI3KCA gene amplification involved only HPV16-negative (13%) cases, while a gain of PI3KCA gene copy number similarly occurred in HPV16-positive (29%) and negative (25%) OSCC. Activating mutations play a marginal role both in HPV16-positive (6%) and negative (2%) OSCC. An higher occurrence of PI3KCA transcript values, 31 folds > than the lower one, was found in HPV16-positive (60%) compared with negative (27%) OSCC (p=0.05). PTEN gene loss was restricted to HPV16-positive (12%) cases, while PTEN mutation similarly involved both HPV16-positive (9%) and negative (10%) OSSC. Overall, PI3KCA and PTEN alterations was more frequent in HPV16- positive (70%) than negative (44%) OSCC. Despite a statistically significant higher occurrence of an increased HER2 gene/chromosome 17 copy number in HPV16-negative (46%) than positive (18%) OSSC (p<0.004), no case showed HER2 expression. IGF-1R cytogenetic analysis revealed a statistically significant higher frequency of increased IGF- 1R/chromosome 15 copy number in HPV16-negative (41%) than positive (7%) OSCC (p=0.02). This is in keeping with the higher occurrence of IGF-1R transcript values, 30 folds > than the lower one, detected in HPV16-negative (73%) than positive (15%) cases (p<0.001). Most OSCC showed expression of the cognate ligands IGF1 and IGF2, however HPV16-negative cases expressed higher IGF1 levels than HPV16-positive OSCC. Conclusions: PI3KCA/PTEN alterations could be responsible to primary EGFRi resistance particularly in HPV16-positive tumors, while IGF-1R could be associated with resistance mainly in HPV16-negative OSCC. HER2 seems not to be involved. Based on our results, resistances to EGFRi should be tackled differently according to HPV tumor status. No significant financial relationships to disclose.

The incidence of patients showing neck metastasis and no obvious primary tumor at the initial diagnostic evaluation or neck cancer of unknown primary (NCUP) is rising. It is estimated that a relevant part of these tumors arises in the tonsillar crypts or base of the tongue and are p16+-related. However, today, the detection rate of the primary tumor is suboptimal. Identifying the primary tumor and its biomolecular characterization is essential since it influences the treatment administered, possibly reducing radiation fields and providing de-escalation to primary surgical management. However, p16 IHC (immunohistochemistry) might not be sufficient to diagnose HPV-related OPSCC. The other subset of patients discussed are the HPV-positive patients who have a history of tobacco exposure and/or p53 mutations. Possible factors that could negatively influence the outcomes of these patients are investigated and discussed below. So, this paper aims to analyze the diagnostic, bio-molecular, clinico-radiological, morphological, prognostic and therapeutical aspects of p16-positive OPSCC, highlighting the possible bias that can occur during the diagnostic and prognostic process. A narrative review was conducted to investigate the biases in the diagnostic and therapeutic process of two groups of patients: those who are p16-positive but HPV-negative patients, and those who are p16-positive and HPV-positive with exposure to traditional risk factors and/or p53 mutations. The keywords used for the literature research included the following: NCUP, OPSCC, p16IHC, HPV testing, p16 positive HPV negative OPSCC, p16 positive HPV positive OPSCC, tonsillectomy, tobacco exposure, p53 mutations, cystic neck metastasis, extranodal extension (ENE), radiotherapy, de-escalation and neck neck dissection. HPV-positive OPSCC has specific clinico-radiological features. Bilateral tonsillectomy should be considered for the identification of the primary tumor. P16 IHC alone is not sufficient for diagnosing HPV-related OPSCC; additional detection methods are required. The role of tobacco exposure and p53 mutations should be investigated especially in cases of HPV-positive tumors. Extranodal extension (ENE) must be taken into consideration in the prognostic staging of HPV-positive tumors. Surgical primary treatment involving neck dissection (ND) and bilateral tonsillectomy followed by adjuvant radiation may represent the most appropriate approach for N3 cases. Diagnosis, prognosis and therapeutical implications must be addressed considering clinical, biomolecular and morphological aspects. At least today, the numerous biases that are still present influencing the diagnostic and prognostic process do not permit considering de-escalation protocols. A precise and accurate diagnosis is required in order to adequately stage and manage p16+ OPSCC, particularly with neck metastasis. The role of tobacco exposure and/or p53 mutations must be considered not only in p16+ OPSCC but especially in HPV-positive OPSCC. Until a more accurate diagnosis is possible, ENE should be considered even in p16+HPV+ OPSCC. Primary surgery with unilateral ND and bilateral tonsillectomy might be the treatment of choice given the numerous diagnostic and prognostic pitfalls. Therefore, it is inappropriate and risky to propose de-escalation protocols in routine clinical practice due to the risk of undertreatment.

Among head and neck squamous carcinoma (HNSC), human papilloma virus (HPV)-driven tumors are known to enjoy more favorable prognostic outcomes compared to non-HPV-driven disease. This is especially true of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), which is associated with significantly improved outcomes compared to HPV-positive non-OPSCC and HPV-negative HNSC. Previous reports have suggested that increased immune infiltration and expression of the estrogen receptor α (ERα) may play a role in conferring improved prognosis to HPV-positive OPSCC. However, the underlying signaling pathways specifically driven by HPV in the oropharynx have remained elusive. Here we analyzed HPV-positive OPSCC and non-OPSCC tumors from The Cancer Genome Atlas (TCGA) and found that HPV-positive OPSCC is associated with significantly improved overall and disease-specific survival and progression-free interval compared to HPV-positive non-OPSCC. Among HPV-positive HNSC, we observed a distinct separation of OPSCC from non-OPSCC tumors based on unsupervised clustering of gene expression, microRNA, and methylation profiling data. Separation based on anatomic site was not observed among HPV-negative HNSC, suggesting that common biology drives the carcinogenesis of HPV-negative HNSC across subsites. In line with a recent report that ERα mRNA expression is elevated HPV-positive OPSCC, we found significantly higher ERα mRNA levels in HPV-positive OPSCC compared to HPV-positive non-OPSCC, where ERα mRNA expression mirrored that in HPV-negative HNSC. We also found that HPV induces downregulation of TGF-β signaling and extracellular matrix (ECM)-associated genes while upregulating a T-cell and dendritic cell-associated immune response signature in an OPSCC-specific manner. Our analyses suggest that HPV induces downregulation of TGF-β signaling and ECM components in OPSCC to improve immune access to these tumors, facilitating tumor clearance and improved patient survival. These findings are in line with our recent report establishing TGF-β-mediated immunosuppression through ECM deregulation and its negative effect on patient prognosis. Citation Format: Anthony Bolyos, Pinaki Bose. Improved prognosis of HPV-positive oropharyngeal cancers is associated with a suppression of TGF-β-mediated immune evasion [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A07.

Pathology-based staging for HPV-positive squamous carcinoma of the oropharynx