Human Papillomavirus Status In Patients Research Articles

210 Using quantitative diffusion-weighted MRI to predict treatment outcome and Human Papillomavirus status in patients with oropharyngeal squamous cell carcinoma

210 Using quantitative diffusion-weighted MRI to predict treatment outcome and Human Papillomavirus status in patients with oropharyngeal squamous cell carcinoma

Cause of Death in Patients with Oropharyngeal Carcinoma by Human Papillomavirus Status: Comparative Data Analysis.

The incidence of oropharyngeal squamous cell carcinomas (OPSCC) has increased in recent decades, and human papillomavirus (HPV) infection is the main cause of OPSCC. The data regarding causes of death (CODs) are vitally important in informing follow-up strategies and revising treatment strategies to deal with any possible preventable treatment-related COD. However, limited studies have assessed the competing COD by HPV status in patients with OPSCC. We aimed to analyze the distribution of the competing COD according to HPV status in OPSCC. We retrospectively included stage I-IVB patients with OPSCC from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. The association between HPV status and head and neck cancer-specific mortality (HNCSM), second primary cancer mortality (SPCM), and noncancer-caused mortality (NCCM) were analyzed. The chi-square test, Kaplan-Meier analysis, and Fine and Gray model were used for statistical analysis. We included 5852 patients in this study and 73.2% (n=4283) of them had HPV-related tumors. A total of 1537 (26.3%) patients died, including 789 (51.3%), 333 (21.7%), and 415 (27%) patients who died from head and neck cancer, second cancer, and noncancer causes, respectively. The 5-year HNCSM, SPCM, NCCM, and overall mortality were 14.7%, 6.5%, 7.7%, and 26.4%, respectively. Those with HPV-positive disease had a lower cumulative incidence of HNCSM (subdistribution hazard ratio [sHR] 0.362, 95% CI 0.315-0.417; P<.001), SPCM (sHR 0.400, 95% CI 0.321-0.496; P<.001), and NCCM (sHR 0.460, 95% CI 0.378-0.560; P<.001) than those with HPV-negative disease. The 5-year risk of HNCSM was 26.9% and 10.7% in those with HPV-negative and HPV-positive disease, respectively (P<.001). The 5-year risk of SPCM was 12.4% and 4.6% in those with HPV-negative and HPV-positive disease, respectively (P<.001). The 5-year risk of NCCM of death was 13.7% and 5.8% in those with HPV-negative and HPV-positive disease, respectively (P<.001). Using the Fine and Gray competing-risks model, our results show that those with HPV-negative tumors had a significantly higher risk of HNCSM (P<.001), SPCM (P<.001), and NCCM (P<.001) than those with HPV-negative tumors. HPV-positive OPSCC has a lower NCSM, SPCM, and NCCM as compared to those with HPV-negative OPSCC. HPV positivity is a favorable prognostic factor in the context of overcoming cancer as well as in terms of reducing the risk of other CODs in OPSCC. Our finding supports the need to tailor patient follow-up based on the HPV status of patients with OPSCC.

D160. HPV-associated Survival and Surgical Management of Advanced Squamous Cell Carcinoma of the Head And Neck

PURPOSE: The increasing incidence of human papillomavirus (HPV)-associated head and neck cancer (HNC) necessitates studies on patient outcomes and survival stratified by HPV status. Many studies have assessed HPV-associated survival across all HNC patients; we compare survival by HPV status for patients with advanced HNC to inform surgical management. METHODS: Adults with malignant squamous cell HNC diagnosed between 2011 and 2017 were identified from the Surveillance, Epidemiology and End Results (SEER) Head and Neck with HPV status database, which includes data from registries covering 47% of the United States population. Patients without HPV status, survival data or histopathologic confirmation of disease were excluded. “Invasive” carcinoma was defined as cancers with T4 staging, as this denotes bone involvement. Kaplan-Meier survival analyses were completed in R Studio (v1. 3.1). RESULTS: The analysis of survival by HPV status and tumor invasiveness included 13,493 patients; of these, 9,087 had HPV-associated disease and 1,564 had invasive disease. Survival analysis of all HNC patients revealed significantly higher 8-year survival for patients with HPV-associated disease than those without (p < 0.01). When analysis was narrowed to patients with T4 disease, no survival difference was found. CONCLUSION: HPV-associated HNC is often considered less severe than non-HPV-associated disease which may lead to more conservative management decisions. However, this first of its kind analysis of HNC subgroups demonstrates the absence of any HPV-associated survival benefit among patients with advanced disease involving the bone. These data suggest that such cancers should be managed with aggressive surgical resection and reconstruction, consistent with management of non-HPV-associated etiologies.

Antitumor immune cycle proteins and HPV status in patients with HSIL and cervical cancer

Background. Cervical cancer (CC) is a common malignant tumor among women worldwide. The anti-tumor immune cycle (AIC) is a necessary molecular mechanism that prevents the occurrence and progression of a tumor. It is known that during the development of CC, several mechanisms disrupt the AIC and contribute to tumor progression. Recent data show the role of human papillomavirus (HPV) in the AIC regulation as a mechanism for the emergence of tumor resistance to the anti-tumor immune response.&#x0D; Aim. To study the levels of AIC proteins (sCD25, 4-1BB, B7.2, TGF-b1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, Galectin-9, sCD27, PD-L2) in patients with high-grade squamous intraepithelial lesion (HSIL) and CC, depending on the HPV status.&#x0D; Materials and methods. A prospective study enrolled women of reproductive age with HSIL (n=53) and stage IIII СС (n=93). The control group included female volunteers without cervical abnormalities (n=30). The study material was the cervical epithelium. Study methods: flow cytometry, diagnostics using the polymerase chain reaction for HPV status and viral load. Statistical processing was performed using the IBM SPSS Statistics version 25.0 software package using non-parametric statistics methods.&#x0D; Results. The obtained data indicate an expression increase of AIC inhibitors: PD-1 and PD-L2 in patients with HPV infection and sCD27 in patients with mono-HPV infection. There were no significant differences in the levels of AIC proteins, depending on the HPV viral load in patients with HSIL and CC.&#x0D; Conclusion. The effect of HPV infection and its type on regulating the expression of specific AIC proteins has been established, which is one of the mechanisms of tumor progression.

18F-FDG PET/CT Parameters Enhance MRI Radiomics for Predicting Human Papilloma Virus Status in Oropharyngeal Squamous Cell Carcinoma.

Predicting human papillomavirus (HPV) status is critical in oropharyngeal squamous cell carcinoma (OPSCC) radiomics. In this study, we developed a model for HPV status prediction using magnetic resonance imaging (MRI) radiomics and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) parameters in patients with OPSCC. Patients with OPSCC who underwent 18F-FDG PET/CT and contrast-enhanced MRI before treatment between January 2012 and February 2020 were enrolled. Training and test sets (3:2) were randomly selected. 18F-FDG PET/CT parameters and MRI radiomics feature were extracted. We developed three light-gradient boosting machine prediction models using the training set: Model 1, MRI radiomics features; Model 2, 18F-FDG PET/CT parameters; and Model 3, combination of MRI radiomics features and 18F-FDG PET/CT parameters. Area under the receiver operating characteristic curve (AUROC) values were used to analyze the performance of the models in predicting HPV status in the test set. A total of 126 patients (118 male and 8 female; mean age: 60 years) were included. Of these, 103 patients (81.7%) were HPV-positive, and 23 patients (18.3%) were HPV-negative. AUROC values in the test set were 0.762 [95% confidence interval (CI), 0.564-0.959], 0.638 (95% CI, 0.404-0.871), and 0.823 (95% CI, 0.668-0.978) for Models 1, 2, and 3, respectively. The net reclassification improvement of Model 3, compared with that of Model 1, in the test set was 0.119. When combined with an MRI radiomics model, 18F-FDG PET/CT exhibits incremental value in predicting HPV status in patients with OPSCC.

The Prognostic and Predictive Effects of Human Papillomavirus Status in Hypopharyngeal Carcinoma: Population-Based Study.

The role of the Human Papillomavirus (HPV) status in patients with hypopharyngeal squamous cell carcinoma (HSCC) remains controversial. Our aim was to determine the prognostic and predictive effects of HPV status in patients with locally advanced HSCC (stage III-IVB) receiving primary radiotherapy. Patients diagnosed with stage III-IVB HSCC between 2010 and 2016 were identified. HPV status, demographics, clinicopathological characteristics, treatment, and survival data were captured. Kaplan-Meier analysis, multivariable Cox regression analysis, and propensity score matching analysis were performed. We identified 531 patients in this study and 142 (26.7%) patients with HPV-positive diseases. No significant differences were observed between those with HPV-negative and HPV-positive diseases with regard to demographics, clinicopathological characteristics, and chemotherapy use. HPV-positive HSCC had better head and neck cancer-specific survival (HNCSS; P=.001) and overall survival (OS; P<.001) compared to those with HPV-negative tumors. Similar results were found using the multivariable Cox regression analysis. Sensitivity analyses showed that the receipt of chemotherapy was associated with significantly improving HNCSS (P<.001) and OS (P<.001) compared to not receiving chemotherapy in HPV-negative HSCC, whereas comparable HNCSS (P=.59) and OS (P=.12) were found between both treatment arms in HPV-positive HSCC. Similar results were found after propensity score matching. Approximately one-quarter of HSCC may be HPV-related, and HPV-positive HSCC is associated with improved survival outcomes. Furthermore, additional chemotherapy appears to be not related to a survival benefit in patients with HPV-positive tumors who received primary radiotherapy.

Prognostic Significance of p16 and Its Relationship with Human Papillomavirus Status in Patients with Penile Squamous Cell Carcinoma: Results of 5 Years Follow-Up.

Penile Squamous Cell Carcinoma (PSCC) is associated with high-risk human papillomavirus (HR-HPV). The immunohistochemical (IHC) test for p16INK4a (p16) is highly correlated with HR-HPV expression in other SCCs. To investigate whether the expression of p16 IHC or HR-HPV is associated with survival in PSCC, we conducted a single institution analysis of 143 patients with a diagnosis of PSCC and, available tissue were tested for p16 IHC staining patterns, histological subtype, tumor grade, and lymphovascular invasion (LVI) by an experienced pathologist. HR-HPV status using the Cobas PCR Assay or the RNAScope high-risk HPV in situ hybridization kit were also assessed. Patient characteristics were summarized using descriptive statistics of clinico-pathologic variables. Kaplan-Meier was used to estimate median overall survival (OS), cancer specific survival (CSS) and correlated with HPV, p16, and other study variables. Patients with p16+ tumors had a significantly longer median CSS in comparison to the p16- group (p = 0.004), with respective 5-year CSS probability of 88% (95% CI; 0.84, 1) versus 58% (95% CI; 0.55, 0.76; p = 0.004). HPV status did not predict survival outcomes. Multivariable analysis with respect to OS and CSS, showed that p16+ status was associated with a lower risk of death (HR = 0.36, 95%CI; 0.20-0.67, p = 0.001), and improved CSS (HR = 0.20, 95% CI; 0.07-0.54, p = 0.002) after adjusting for covariates. In conclusion, tumor p16 status via IHC was an easy to perform independent prognostic factor for OS and CSS that correlates with HR-HPV expression.

Amide proton transfer imaging for the determination of human papillomavirus status in patients with oropharyngeal squamous cell carcinoma.

The aim of this study was to investigate the utility of amide proton transfer (APT) imaging for the determination of human papillomavirus (HPV) status in patients with oropharyngeal squamous cell carcinoma (SCC). Thirty-one patients with oropharyngeal SCC were retrospectively evaluated. All patients underwent amide proton transfer imaging using a 3T magnetic resonance (MR) unit. Patients were divided into HPV-positive and -negative groups depending on the pathological findings in their primary tumor. In APT imaging, the primary tumor was delineated with a polygonal region of interest (ROI). Signal information in the ROI was used to calculate the mean, standard deviation (SD) and coefficient of variant (CV) of the APT signals (APT mean, APT SD, and APT CV, respectively). The value of APT CV in the HPV-positive group (0.43 ± 0.04) was significantly lower than that in the HPV-negative group (0.48 ± 0.04) (P = .01). There was no significant difference in APT mean (P = .82) or APT SD (P = .13) between the HPV-positive and -negative groups. Receiver operating characteristic (ROC) curve analysis of APT CV had a sensitivity of 0.75, specificity of 0.8, positive predictive value of 0.75, negative predictive value of 0.8, accuracy of 0.77 and area under the curve (AUC) of 0.8. The APT signal in the HPV-negative group was considered heterogeneous compared to the HPV-positive group. This information might be useful for the determination of HPV status in patients with oropharyngeal SCC.

Histogram analysis of arterial spin labeling perfusion data to determine the human papillomavirus status of oropharyngeal squamous cell carcinomas.

To evaluate the correlation between histogram parameters derived from pseudo-continuous arterial spin labeling (PCASL) and human papillomavirus (HPV) status in patients with oropharyngeal squamous cell carcinoma (OPSCC). This study included a total of 58 patients (HPV-positive: n = 45; -negative: n = 13) from a prospective cohort of consecutive patients aged ≥ 18years, who were newly diagnosed with oropharyngeal squamous cell carcinoma. All patients were required to have undergone pre-treatment MRI with PCASL to measure regional perfusion. The region of interest was drawn by two radiologists, encompassing the entire tumor volume on all corresponding slices. Differences in the histogram parameters derived from tumor blood flow (TBF) in ASL were assessed for HPV-positive and -negative patients. Receiver operating characteristic curve analysis was performed to determine the best differentiating parameters, and a leave-one-out cross-validation was used. Patients with HPV-positive OPSCC showed a significantly lower overall standard deviation and 95th percentile value of tumor blood flow (P < .007). The standard deviation of TBF was the single best predictive parameter. Leave-one-out cross-validation tests revealed that the area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity were 0.745, 75.9%, 75.6%, and 76.9%, respectively. PCASL revealed differences in perfusion parameters according to HPV status in patients with OPSCC, reflecting their distinct histopathology.

Prediction of the human papillomavirus status in patients with oropharyngeal squamous cell carcinoma by FDG-PET imaging dataset using deep learning analysis: A hypothesis-generating study

PurposeTo assess the diagnostic accuracy of imaging-based deep learning analysis to differentiate between human papillomavirus (HPV) positive and negative oropharyngeal squamous cell carcinomas (OPSCCs) using FDG-PET images. MethodsOne hundred and twenty patients with OPSCC who underwent pretreatment FDG-PET/CT were included and divided into the training 90 patients and validation 30 patients cohorts. In the training session, 2160 FDG-PET images were analyzed after data augmentation process by a deep learning technique to create a diagnostic model to discriminate between HPV-positive and HPV-negative OPSCCs. Validation cohort data were subsequently analyzed for confirmation of diagnostic accuracy in determining HPV status by the deep learning-based diagnosis model. In addition, two radiologists evaluated the validation cohort image-data to determine the HPV status based on each tumor’s imaging findings. ResultsIn deep learning analysis with training session, the diagnostic model using training dataset was successfully created. In the validation session, the deep learning diagnostic model revealed sensitivity of 0.83, specificity of 0.83, positive predictive value of 0.88, negative predictive value of 0.77, and diagnostic accuracy of 0.83, while the visual assessment by two radiologists revealed 0.78, 0.5, 0.7, 0.6, and 0.67 (reader 1), and 0.56, 0.67, 0.71, 0.5, and 0.6 (reader 2), respectively. Chi square test showed a significant difference between deep learning- and radiologist-based diagnostic accuracy (reader 1: P = 0.016, reader 2: P = 0.008). ConclusionsDeep learning diagnostic model with FDG-PET imaging data can be useful as one of supportive tools to determine the HPV status in patients with OPSCC.

Correlation between tumour biology status measured in triple-tracer 18F-fluorodeoxyglucose-18F-fluorothymidine- 18F-fluoromisonidazole-PET/CT study and human papillomavirus status in patients with head and neck cancer.

Human papillomavirus (HPV) has been usually associated with gynaecological cancers; however, recent studies have shown that this virus plays an important role in head and neck cancer. The aim of this study was to correlate PET/CT parameters in HPV-positive (HPV) and HPV-negative (HPV) patients using three tracers showing glucose metabolism, proliferation and hypoxia. Thirty-six patients (10 females and 26 males) with newly diagnosed head and neck cancer were enroled to this retrospective study. All patients underwent a series of three PET/CT scans with fluorine-18-fluorodeoxyglucose (F-FDG), fluorine-18-fluorothymidine (F-FLT) and fluorine-18-fluoromisonidazole (F-FMISO). Scans were performed on separate days, within a time-frame of 2 weeks. We compared several PET/CT parameters grading tumour biology including maximum standardized uptake value (SUV), total lesion glycolysis, totalSUV and heterogeneity between HPV and HPV patients. For statistical analysis, t-test and Mann-Whitney test were used and the materiality level of P values less than 0.05 were considered significant. Patient with HPV showed higher SUV values than patients with HPV in F-FLT images (6.34±2.5 vs. 5.99±3.6) and F-FMISO images (1.66±0.33 vs. 1.62±1.28) and lower values in F-FDG images (9.99±3.85 vs. 10.28±2.44). However, analyzing total lesion glycolysis values in all tracers, HPV patients showed higher values than HPV patients [F-FDG (92.21±102.9 vs. 70.83±74.27), F-FMISO (30.75±30.1 vs. 25.13±31.34) and F-FLT (138.71±132.9 vs. 109.61±92.7)]. In our preliminary and limited study, we did not observe statistically significant differences in tumour metabolism, proliferation and hypoxia between the HPV and HPVpatients. However HPV patients tend to have higher proliferation status and more pronounced hypoxia with lower glucose metabolism.

HPV status in patients with nasopharyngeal carcinoma in the United States: A SEER database study.

To investigate the etiologic and prognostic role of Human Papilloma Virus (HPV) in Nasopharyngeal Carcinoma (NPC). Patients diagnosed with NPC were identified with the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was used to investigate the effect of clinicopathologic predictors on HPV positivity in NPC. Survival analyses were performed with Kaplan-Meier curves and Cox regression models. 180/517 patients (34.8%) with known HPV testing were positive for HPV-associated NPC. East Asians and individuals over 25 were less likely to have HPV-associated NPC, while controlling for AJCC-7 stage and AJCC-7 M stage. According to the survival analysis, cause-specific survival (CSS) did not differ significantly by HPV status throughout the study period, but did differ significantly by HPV ethnicity group. The clinical implications of HPV in NPC are further elucidated but require more investigation. IV.

Prognostic implications of human papillomavirus status for patients with non-oropharyngeal head and neck squamous cell carcinomas.

We examined overall survival in a large cohort of patients with human papillomavirus (HPV)-positive and HPV-negative non-oropharyngeal squamous cell carcinoma of the head and neck (non-OPSCC). Patients diagnosed with non-OPSCC and known HPV status were identified in the National Cancer Database (NCDB). Multivariate logistic regression was applied to examine factors associated with HPV status. Multivariate analysis was utilized to determine factors correlated with overall survival. Propensity score-weighted Kaplan-Meier estimation was used to adjust for confounders in survival analyses. Multiple imputation method was used for sensitivity analysis. We identified 19,993 non-OPSCC patients with 5070 being positive for HPV in the NCDB. Median follow-up was 23.5months. HPV-positive patients were more commonly male, white, with a lower comorbidity index score, presenting with T-stage <2, and N-stage ≥1. Unadjusted 3-year overall survival was 62% and 80% for HPV-negative and HPV-positive patients, respectively (p<0.0001). On multivariate analysis, mortality was reduced for HPV-positive patients with early stage (HR=0.68) and locally advanced disease (HR=0.46). Adjusted 3-year overall survival was 65% for HPV-negative and 76% for HPV-positive patients (p<0.0001). The survival advantage of HPV was maintained in all subsites and robust on sensitivity analysis. Patients with HPV-positive non-OPSCC exhibit similar characteristics as HPV-positive OPSCC. Overall survival was significantly higher for patients with HPV-positive versus HPV-negative non-OPSCC. These data reveal that HPV-positive non-OPSCC represent a favorable cohort that warrants recognition in the design of future clinical trial investigation.

P16, HPV, and Cetuximab: What Is the Evidence?

Human papillomavirus (HPV) status (or its commonly utilized surrogate p16) is a known prognostic biomarker in oropharyngeal squamous-cell carcinoma of the head and neck (SCCHN). We evaluated implications of the available evidence, including cetuximab registration trials in previously untreated locoregionally advanced (LA) SCCHN and recurrent and/or metastatic (R/M) SCCHN. We conclude that, although p16 and HPV are prognostic biomarkers for both LA and R/M SCCHN, they have not been shown to be predictive of response to the described cetuximab-containing regimens for either indication. Thus, current evidence suggests that benefits of cetuximab are observed in both p16-/HPV-positive and -negative SCCHN.

Erratum to: Variants of EVER1 and EVER2 (TMC6 and TMC8) and human papillomavirus status in patients with mucosal squamous cell carcinoma of the head and neck.

There is a growing association of human papillomavirus (HPV) with some cases of mucosal squamous cell carcinoma of the head and neck (HNSCC), particularly of the oropharynx. Persistent oral HPV infection is believed to increase the likelihood of malignancy, and it is possible that host genetic factors can determine susceptibility to persistent HPV infection. Polymorphisms in the two EV genes (EVER1 and EVER2, also known as transmembrane channel protein (TMC) 6 and 8) have been identified as strong candidate genes, since a small number of critical mutations in these genes have been shown to cause profound and florid skin HPV infections, and some of them have been linked to susceptibility to cervical cancer. We sought to determine whether there was a difference in the frequency of single nucleotide polymorphisms (SNPs) in EVER1 (rs2613516, rs12449858) and EVER2 (rs7205422, rs12452890) between HNSCC patients with HPV-positive and HPV-negative tumors, and healthy controls. We used logistic regression to analyze SNPs in 219 patients with histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx, or larynx, and 321 healthy controls. We did not find any associations with the EVER1/EVER2 SNPs and HPV status or being a HNSCC case or a control. The present data do not provide evidence for a role of genetic variations in EVER1 or EVER2 for HPV status of mucosal HNSCC or between HNSCC patients and controls.

Evaluation of the Prevalence Rate and the Prognostic Effect of Human Papilloma Virus Infection in a Group of Patients With Oral Cavity Squamous Cell Carcinoma.

BackgroundSquamous cell carcinoma (SCC) is the most common malignancy of the oral cavity. A relationship between the human papilloma virus (HPV) infection and the prognosis of oral cavity SCC (OCSCC) has been discussed before.ObjectivesWe investigated the prevalence rate of HPV status in patients with OCSCC, and its effects on clinicopathological characteristics of tumors and patients’ prognosis.Patients and MethodsSections of formalin-fixed, paraffin-embedded tissue blocks from 114 histopathologically confirmed OCSCC cases were investigated in this study. Polymerase chain reaction (PCR) was applied to evaluate the HPV status in the samples.ResultsFifteen (13.16%) cases were identified as HPV positive. The detected viral subtypes in this study were the subtypes 6 and 11. The stage and especially lymph node stage was significantly higher in the HPV positive group compared to the HPV negative group (P = 0.04). Disease free survival (DFS) was remarkably lower in the HPV positive group compared to the HPV negative group (13.9 vs. 49.9 months, P = 0.02). Overall survival (OS) was also significantly inferior in the HPV positive group (15.7 vs. 49.6 months, P = 0.01). In the current study, no significant differences were observed between two groups in relation to the variables of age, gender, tumors site, tumor size, tumor grading and also the recurrence rate.ConclusionsThe observed higher mortality rate among the HPV positive group indicates the poorer prognosis of this group in comparison with the HPV negative patients. The incidence rate of HPV infection was low in the studied samples; however, interaction of subtypes 6 and 11 of HPV in poorer prognosis of the patients and a carcinogenic role of HPV in OCSCC cannot be ruled out.

Variants of EVER1 and EVER2 (TMC6 and TMC8) and human papillomavirus status in patients with mucosal squamous cell carcinoma of the head and neck.

There is a growing association of human papillomavirus (HPV) with some cases of mucosal squamous cell carcinoma of the head and neck (HNSCC), particularly of the oropharynx. Persistent oral HPV infection is believed to increase the likelihood of malignancy, and it is possible that host genetic factors can determine susceptibility to persistent HPV infection. Polymorphisms in the two EV genes (EVER1 and EVER2, also known as transmembrane channel protein (TMC) 6 and 8) have been identified as strong candidate genes, since a small number of critical mutations in these genes have been shown to cause profound and florid skin HPV infections, and some of them have been linked to susceptibility to cervical cancer. We sought to determine whether there was a difference in the frequency of single nucleotide polymorphisms (SNPs) in EVER1 (rs2613516, rs12449858) and EVER2 (rs7205422, rs12452890) between HNSCC patients with HPV-positive and HPV-negative tumors, and healthy controls. We used logistic regression to analyze SNPs in 219 patients with histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx, or larynx, and 321 healthy controls. We did not find any associations with the EVER1/EVER2 SNPs and HPV status or being a HNSCC case or a control. The present data do not provide evidence for a role of genetic variations in EVER1 or EVER2 for HPV status of mucosal HNSCC or between HNSCC patients and controls.

Prognostic value of p16 expression irrespective of human papillomavirus status in patients with oropharyngeal carcinoma.

In a previous study, we reported the value of p16 expression and alcohol consumption in oropharyngeal carcinoma in Japan. We now report the clinical significance of human papillomavirus status and p16 expression in oropharyngeal carcinoma in Japan. Over a 9-year period, a retrospective case comparison study of the pathology database was conducted at the University of Tokyo to identify tumor samples of oropharyngeal carcinoma. We performed immunohistochemistry for the p16 protein, in situ hybridization for human papillomavirus-deoxyribonucleic acid and polymerase chain reaction for the human papillomavirus-deoxyribonucleic acid oncogene E6 in oropharyngeal carcinoma in Japanese patients. We evaluated the human papillomavirus status in patients with oropharyngeal carcinoma to determine its prevalence and association with prognosis. We defined human papillomavirus(+) and human papillomavirus(-) oropharyngeal carcinoma cohorts as those with and without polymerase chain reaction for the human papillomavirus-deoxyribonucleic acid oncogene E6 or in situ hybridization-human papillomavirus. In oropharyngeal carcinoma, the prevalences of p16(+)human papillomavirus(+), p16(+)human papillomavirus(-), p16(-)human papillomavirus(+) and p16(-)human papillomavirus(-) were 32% (48/150), 7% (10/150), 2% (3/150) and 59% (89/150), respectively. Low tobacco and alcohol consumption, tonsil or base of tongue localization, but not age, were associated with p16(+)human papillomavirus(+). Low alcohol consumption was associated with p16(+)human papillomavirus(-). There was a significant difference in overall survival between p16(+)human papillomavirus(-) and p16(-)human papillomavirus(-) (P = 0.03). In multivariate Cox regression models, p16 was the independent prognostic factor, regardless of human papillomavirus status. p16 expression was a reliable prognostic biomarker regardless of human papillomavirus status.

What is the role of human papillomavirus testing in head and neck cancer?

What is the role of human papillomavirus testing in head and neck cancer?

Cervista HPV assays for fine-needle aspiration specimens are a valid option for human papillomavirus testing in patients with oropharyngeal carcinoma.

The objectives of this study were to evaluate the validity of Cervista human papillomavirus (HPV) assays in head and neck fine-needle aspiration (FNA) specimens from patients with head and neck squamous carcinomas and to verify that the Cervista assay in FNA specimens is a valid option for determining HPV status in patients with oropharyngeal carcinomas. The authors retrospectively retrieved 64 head and neck FNA specimens from patients who had head and neck squamous carcinoma. The specimens were tested for HPV types 16 and 18 (HPV16/18) and for high-risk (HR) HPV DNA using the Cervista HPV16/18 and HPV HR assays, respectively. The results from those assays were compared with the results from polymerase chain reaction (PCR)-based HPV assays in the same tissues and with the results from HPV in situ hybridization assays/p16 immunostaining in the corresponding primary tumors. In total, 64 FNA specimens were analyzed. The Cervista HPV16/18 and/or HPV HR assays were positive in 48 of 64 specimens (75%), and there was a predominance of HPV16 (42 of 48 specimens; 88%). In the 49 specimens that had PCR-based test results, overall agreement with Cervista assay results was 96% (47 of 49 specimens; κ = 0.883). In the 49 specimens that had PCR-based HPV16/18 genotyping results, overall agreement with the Cervista HPV16/18 results was 94% (46 of 49 specimens; κ = 0.847). In the 36 primary carcinoma specimens that had valid HPV in situ hybridization/p16 immunostaining results, overall agreement with the Cervista assay results was 92% (33 of 36 specimens; κ = 0.679). Cervista HPV16/18 and Cervista HPV HR testing of head and neck FNA specimens is a valid option for determining HPV16/18 status in patients with oropharyngeal carcinoma.