HPV-positive Oropharyngeal Cancer Patients Research Articles

The role of HPV on the risk of second primary neoplasia in patients with oropharyngeal carcinoma

ObjectivesIt has been reported that patients with HPV-positive oropharyngeal cancer (OPC) have a lower risk of appearance of second primary neoplasm (SPN) than HPV-negative OPC patients. The aim of our study was to analyze the risk of developing SPN in a large group of patients with OPC according to HPV status in the primary tumor. Materials and methodsWe included 412 OPC patients treated at our center from 1991 to 2014 for which the HPV DNA positivity was evaluated by PCR in available tumor specimens. HPV DNA positive samples were further tested for HPV E6∗I mRNA detection and/or p16INK4a immunohistochemistry. We estimated the incidence of SPN in all cancer sites and in cancer sites related to tobacco and alcohol consumption according to the HPV status in the primary tumor. ResultsFifty-one (12.4%) out of 412 OPCs included in the study were HPV-related. Five-year SPN-free survival for HPV-negative versus HPV-positive OPC patients was 57.0% and 89.0% (P<0.001), respectively. Corresponding estimates for 10-year SPN-free survival were 35.2% versus 78.5% (P<0.001). When restricting the analyses to tobacco/alcohol-related SPNs, the corresponding survival rates where 62.0% versus 97.6% (P<0.001) and 42.2% versus 97.6%, (P<0.001), for 5-year and 10-year survival rates, respectively. HPV status and previous toxic habits might allow classifying patients regarding the risk of tobacco/alcohol-related SPNs. ConclusionHPV-related OPC patients have a significant lower risk of SPN development, particularly in those locations related to tobacco use or alcohol consumption.

Association Between Hepatitis C Virus and Head and Neck Cancers.

Hepatitis C virus (HCV) infection is associated with hepatocellular carcinoma and non-Hodgkin's lymphoma. In 2009, MD Anderson established the first US clinic for treating HCV-infected cancer patients, where we observed an unexpectedly large number of patients with head and neck cancers (HNCs). We sought to determine whether HCV is associated with HNCs. In this case-control study, medical records of cancer patients tested for HCV antibodies at our center from 2004 through 2014 were identified. Case subjects had new-onset primary oropharyngeal or nonoropharyngeal (oral cavity, nasopharynx, hypopharynx, or larynx) HNCs. Control subjects had smoking-associated (lung, esophagus, or urinary bladder) cancers. Biopsy reports of oropharyngeal cancers tested for human papillomavirus (HPV) were reviewed. Patients with lymphoma were excluded. Multivariable logistic regression models were constructed. All statistical tests were two-sided. Of 34 545 cancer patients tested for HCV antibodies, 409 case subjects (164 oropharyngeal and 245 nonoropharyngeal) and 694 control subjects (378 lung, 168 esophagus, and 148 urinary bladder) were studied. The prevalence of HCV seropositivity was higher in oropharyngeal cancer patients (14.0%, 95% confidence interval [CI] = 8.7% to 19.4%, vs 6.5%, 95% CI = 4.6% to 8.3%), particularly HPV-positive oropharyngeal cancer patients (16.9%, 95% CI = 8.7% to 24.9%, vs 6.5%, 95% CI = 4.6% to 8.3%), and nonoropharyngeal HNC patients (20.0%, 95% CI = 14.9% to 25.0%, vs 6.5%, 95% CI = 4.6% to 8.3%) than in control subjects. Adjusted models showed a statistically significant association of HCV seropositivity with nonoropharyngeal (except nasopharyngeal) HNCs (odds ratio [OR] = 2.85, 95% CI = 1.38 to 5.88) and HPV-positive oropharyngeal cancers (OR = 2.97, 95% CI = 1.31 to 6.76). HCV is associated with nonoropharyngeal (except nasopharyngeal) and HPV-positive oropharyngeal HNCs. Further studies are required to explore the possible interaction between HCV and HPV, and the association between HCV and other HPV-related malignancies.

Abstract C92: Systematic review of the literature confirms disparities in the prevalence of HPV-positive oropharynx cancer between African Americans and U.S. whites

Abstract Background: Head and neck cancer (HNC) includes cancers of the oral cavity, larynx and pharynx (which include the oropharynx) and is the sixth most common cancer in the world. Approximately 52,610 new cases and 11,500 deaths from HNC were expected in the United States in 2012. Tobacco and alcohol use are the primary risk factors for developing HNC and human papillomavirus (HPV) is etiologically linked to the majority of oropharynx cancers. HPV-positive oropharyngeal cancer patients have been shown to have improved survival rates compared to HPV-negative patients. It has been suggested that the noted disparity in oropharyngeal cancer survival between African-Americans and Caucasians is due to a lower prevalence of HPV-positive oropharynx tumors in African-American patients. To date this documentation has been limited to only a few small studies. Purpose: In this study we have conducted a systematic review and meta-analysis of the literature to confirm whether a racial disparity in the prevalence of HPV-positive tumors exists between African Americans and US Whites. Results: All articles conducted in the United States that report HPV prevalence by direct evaluation of HNC tissues were included in this study. Studies that evaluated p16 status or HPV serological status as a surrogate marker for HPV-positive HNC were not included. Ninety-four studies were identified which included data for 9,144 cases. There were 15 studies (278 cases) that reported HPV status of HNC from African American patients while 24 studies (2,853 cases) reported HPV status of HNC from White patients. For all other studies race-specific prevalence of HPV was indistinguishable. Preliminary analyses show that overall for African Americans the meta prevalence of HPV-positive HNC was 17.8%, (95% Confidence interval[CI], 13.4-23.3). No heterogeneity was observed between studies (Q-test p-value = 0.172, I-squared = 26%, 0-61). Stratification of these data according to oropharynx and non-oropharynx sub-sites did not result in significant differences (meta prevalence: oropharynx = 18.8%, 95% CI, 10.2-32.1; non-oropharynx = 17.8%, 95% CI, 10.6-28.3). There was also no evidence of heterogeneity between the studies and no evidence of publication bias was observed (Eggers-test p-value, 0.224). In contrast the meta prevalence of HPV-positive HNC in US Whites was 42.7%, 95% CI, 34.7-51.1 but there was large heterogeneity between the studies (Q-test p-value &amp;lt;0.0001, I-squared &amp;gt; 90%). Stratification of the studies between oropharynx and non-oropharynx sub-sites did not resolve the heterogeneity between the studies. There was also no evidence of publication bias (Eggers-test p-value, 0.993). Further investigations are ongoing. Conclusions: Our preliminary findings show that disparity HPV-positive oropharyngeal cancers exist between African Americans and US Whites. The lower prevalence of HPV in African Americans diagnosed with oropharyngeal cancer may explain in part the poor outcomes observed in these populations. Further investigations of possible reasons for this disparity are needed. Citation Format: Camille Ragin Ragin, Gieira Jones, Olubunmi Shoyele, Michael Esan, Denise Gibbs, Jeffery Liu, Samuel Gathere, Emanuela Taioli. Systematic review of the literature confirms disparities in the prevalence of HPV-positive oropharynx cancer between African Americans and U.S. whites. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C92. doi:10.1158/1538-7755.DISP13-C92

Mid-Treatment PET During Radiation Therapy in HPV-Positive Oropharyngeal Cancer Patients Demonstrates Variable Response: Implications for Treatment De-escalation: Imaging

HPV associated oropharyngeal squamous cell carcinomas are known to have a good prognosis and treatment de-escalation is an area of active study. Other disease sites, such as lung cancer (ie, RTOG 11-06) are attempting to use mid-treatment PET/CT scans to try and guide decisions on treatment intensification. We sought to determine patterns of response from a mid-treatment PET/CT in HPV positive or pharyngeal cancer patients to see if this may serve as a biomarker to better determine appropriate candidates for treatment de-escalation. Between 4/2011 and 5/2013, 53 patients had a mid-treatment PET/CT during their course of head and neck radiation therapy at Memorial-Sloan Kettering Cancer Center. All patients were treated with IMRT with or without concurrent cisplatin-based chemotherapy. HPV status was determined by p16 IHC. The highest standardized uptake value (SUV) of both the gross primary and gross nodal disease was recorded before, during and after radiation therapy. The percentage difference of the SUV values on the early response PET and pre radiation PET was used determine the early PET response. A CR was determined to be complete resolution of FDG activity, any decrease in FDG activity was considered a PR, and no response was determined to be no change or an increase in FDG activity. Of the 53 patients, 23 had oropharyngeal primaries. 5 patients were excluded because of induction chemotherapy (n=2), HPV status unavailable (n=2), and HPV negative status (n=1). Of the remaining 18 HPV+ patients, 13 had a BOT primary and 5 had a tonsil primary. 17 patients were stage IVA and 1 patient was stage III. Mid-treatment PET/CT was performed at a median of 43 days after start of treatment (range 34-52). At the primary site, 5 patients had a complete response, 10 patients had a partial response, and 2 patients had no response. No patient with >10 pack -yr smoking history had a CR at the primary site on early response PET. In the neck, 4 patients had a CR and 14 patients had a PR. Individually, 51 nodes were evaluable in these 18 patients. 23 nodes had a CR, 25 nodes had a PR, while 3 nodes had no response. Preliminary results from our study indicate that mid-treatment response PET scans demonstrated variability in response of HPV+ tumors near doses of 60Gy. Given the variability of PET response, caution should be exercised to routinely implement dose de-escalation to all HPV+ oropharyngeal cancer. This information may have implications for treatment de-escalation strategies and further study is warranted to confirm these results.

Potentially functional variants ofp14ARFare associated with HPV-positive oropharyngeal cancer patients and survival after definitive chemoradiotherapy

Since p14 (ARF) and human papillomavirus (HPV) 16 E6/E7 oncoproteins are important regulators participating in the p53/Rb pathways, genetic variations of p14 (ARF) may modify tumor HPV16 status and survival of HPV16-positive squamous cell carcinoma of the oropharynx (SCCOP) patients. We determined tumor HPV16 status and expression of p14/p53 and genotyped p14 (ARF) -rs3731217 and -rs3088440 polymorphisms in 552 incident SCCOP patients. We found that patients having variant genotypes for each p14 (ARF) polymorphism were approximately two or three times as likely to have HPV16-positive tumors compared with patients with corresponding common homozygous genotype, and such an association was particularly pronounced in patients with variant genotypes of both polymorphisms. After definitive chemoradiotherapy, patients having p14 (ARF) rs3731217 TG/GG variant genotypes had significantly better overall, disease-specific and disease-free survival than those having TT genotype, respectively. Multivariable analysis found that patients with p14 (ARF) -rs3731217 TT genotype had an ~7-, 11- and 3-fold increased risk for death overall, death due to SCCOP and recurrence than those with TG/GG variant genotypes, respectively. Furthermore, such significantly prognostic effect was also found when survival analysis was limited to HPV16-positive patients. Additionally, potentially functional relevance of the two variants was characterized to explore the genotype-phenotype correlation. Our findings indicate p14 (ARF) variants may predict tumor HPV16-positive SCCOP patients and survival.

Epidemiology and Clinical Aspects of HPV in Head and Neck Cancers

Human papillomavirus (HPV) infection is now established as a major etiologic factor for oropharyngeal cancers. Case-control studies conducted around the world show strong and consistent associations of markers of HPV exposure with risk of oropharyngeal cancers (range of odds ratios [OR] for oral oncogenic HPV infections = 3.6-230.0, ORs for HPV16 L1 antibodies = 2.3-182.0, and ORs for HPV16 E6/E7 antibodies = 9.2-231.0. HPV-positive oropharyngeal cancers are epidemiologically distinct from HPV-negative ones, and are characterized by younger age at onset, male predominance, and strong association with sexual behaviors. Importantly, HPV-positive oropharyngeal cancer patients have substantially improved outcomes (28-80 % reductions in the risk of death) than HPV-negative patients. Given the superior survival, younger age, and good performance status of HPV-positive oropharyngeal cancer patients, de-intensified therapies are currently being considered for this group of patients. Recent analyses of cancer registry data show dramatic increases in incidence of oropharyngeal cancers during the past 15-20 years in several parts of the world, highlighting the need for prevention strategies. If proven efficacious, currently available prophylactic HPV vaccines hold great promise for primary prevention of HPV-associated oropharyngeal cancers.

Lessons from Australia: Human Papillomavirus Is Not a Major Risk Factor for Esophageal Squamous Cell Carcinoma

The incidence of esophageal cancer exhibits great geographic diversity, with up to 20-fold differences in rates between high- and low-risk areas ([1][1]). Despite stable or even declining worldwide esophageal cancer rates over the last few decades ([2][2], [3][3]), this disease remains a substantial

Racial Survival Disparity in Head and Neck Cancer Results from Low Prevalence of Human Papillomavirus Infection in Black Oropharyngeal Cancer Patients

The burden of squamous cell carcinoma of the head and neck (SCCHN) is greater for blacks than for whites, especially in oropharyngeal cases. We previously showed retrospectively that disease-free survival was significantly greater in white than in black SCCHN patients treated with chemoradiation, the greatest difference occurring in the oropharyngeal subgroup. Oropharyngeal cancer is increasing in incidence and in its association with human papillomavirus (HPV) infection; HPV-positive oropharyngeal cancer patients have significantly better outcomes (versus HPV-negative). These collective data led to the present analyses of overall survival (OS) in our retrospective cohort and of OS and HPV status (tested prospectively in pretreatment biopsy specimens) in the phase 3, multicenter TAX 324 trial of induction chemotherapy followed by concurrent chemoradiation in SCCHN patients. Median OS in the retrospective cohort of 106 white and 95 black SCCHN patients was 52.1 months (white) versus only 23.7 months (black; P = 0.009), due entirely to OS in the subgroup of patients with oropharyngeal cancer--69.4 months (whites) versus 25.2 months (blacks; P = 0.0006); no significant difference by race occurred in survival of non-oropharyngeal SCCHN (P = 0.58). In TAX 324, 196 white patients and 28 black patients could be assessed for HPV status. Median OS was significantly worse for black patients (20.9 months) than for white patients (70.6 months; P = 0.03) and dramatically improved in HPV-positive (not reached) versus HPV-negative (26.6 months, 5.1 hazard ratio) oropharyngeal patients (P < 0.0001), 49% of whom were HPV-16 positive. Overall, HPV positivity was 34% in white versus 4% in black patients (P = 0.0004). Survival was similar for black and white HPV-negative patients (P = 0.56). This is the first prospective assessment of confirmed HPV status in black versus white SCCHN patients. Worse OS for black SCCHN patients was driven by oropharyngeal cancer outcomes, and that for black oropharyngeal cancer patients by a lower prevalence of HPV infection. These findings have important implications for the etiology, prevention, prognosis, and treatment of SCCHN.