The Impact of HPV as an Etiological Factor in Gynecological and Oropharyngeal Cancer.
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ABSTRACT:
SUBMITTER: Manon R
PROVIDER: S-EPMC6125059 | biostudies-other | 2016 Jul-Aug
REPOSITORIES: biostudies-other
Publications
The Impact of HPV as an Etiological Factor in Gynecological and Oropharyngeal Cancer.
Mañon Rafael R Schimp Veronica V Gopalan Priya P Pattani Kavita K Tseng Jennifer J
American journal of lifestyle medicine 20150212 4
The human papilloma virus (HPV) is one of several viral pathogens linked to human cancer. This article reviews the current worldwide cancer burden related to this pathogen. The article also examines the role of HPV in oropharyngeal and gynecological malignancies, current treatment implications, and future directions in the treatment and prevention of HPV-related disease. ...[more]
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Project description:Squamous cell carcinoma of the oropharynx is increasing in incidence in epidemic proportion. This site specific increase in incidence is due to an increase in human papillomavirus (HPV)-related squamous cell carcinoma, while the incidence of tobacco related squamous cell carcinoma is decreasing. In particular, the incidence of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is increased among middle aged white men, and sexual behavior is a risk factor. HPV-related oropharyngeal squamous cell carcinoma represents a growing etiologically distinct subset of head and neck cancers with unique epidemiological, clinical, and molecular characteristics that differ from those of HPV-unassociated cancers. In this review, we discuss the epidemiology of HPV-related OPSCC, the prevalence of oral/oropharyngeal HPV infection, and efforts aimed at reducing the incidence of HPV-related OPSCC.
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Project description:Given the different nature and better outcomes of oropharyngeal carcinoma (OPC) associated with human papillomavirus (HPV) infection, a novel clinical stage classification for HPV-related OPC has been accepted for the 8th edition AJCC TNM (ICON-S model). However, it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value.The aim of this study was to compare different staging system models proposed for HPV-related OPC patients: 7th edition AJCC TNM, RPA stage with non-anatomic factors (Princess Margaret), RPA with N categories for nasopharyngeal cancer (MD-Anderson) and AHR-new (ICON-S), according to different HPV-relatedness definitions: HPV-DNA detection plus an additional positive marker (p16INK4a or HPV-mRNA), p16INK4a positivity alone or the combination of HPV-DNA/p16INK4a positivity as diagnostic tests.A total of 788 consecutive OPC cases diagnosed from 1991 to 2013 were considered eligible for the analysis. Of these samples, 66 (8.4%) were positive for HPV-DNA and (p16INK4a or HPV-mRNA), 83 (10.5%) were p16INK4a positive and 58 (7.4%) were double positive for HPV-DNA/p16INK4a. ICON-S model was the staging system, which performed better in our series when using at least two biomarkers to define HPV-causality. When the same analysis was performed considering only p16INK4a-positivity, RPA stage with non-anatomic factors (Princess Margaret) has the best classification based on AIC criteria.HPV-relatedness definition for classifying HPV-related OPC patient do impact on TNM classification and patients' survival. Further studies assessing HPV-relatedness definitions are warranted to better classify HPV-related OPC patients in the era of de-escalation clinical trials.
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Project description:Squamous cell carcinoma of the head and neck (HNSCC) consist of two distinct biological entities. While the numbers of classical, tobacco-induced HNSCC are declining, tumors caused by human papillomavirus (HPV) infection are increasing in many countries. HPV-positive HNSCC mostly arise in the oropharynx and are characterized by an enhanced sensitivity towards radiotherapy and a favorable prognosis. To identify molecular differences between both entities on the protein level, we conducted a mass spectrometric comparison of eight HPV-positive and nine HPV-negative oropharyngeal tumors (OPSCC). Overall, we identified 2051 proteins, of which 31 were found to be differentially expressed. Seventeen of these can be assorted to three functional groups, namely DNA replication, nuclear architecture and cytoskeleton regulation, with the differences in the last group potentially reflecting an enhanced migratory and invasive capacity. Furthermore, a number of identified proteins have been described to directly impact on DNA double-strand break repair or radiation sensitivity (e.g., SLC3A2, cortactin, RBBP4, Numa1), offering explanations for the differential prognosis. The unequal expression of three proteins (SLC3A2, MCM2 and lamin B1) was confirmed by immunohistochemical staining using a tissue microarray containing 205 OPSCC samples. The expression levels of SLC3A2 and lamin B1 were found be of prognostic relevance in patients with HPV-positive and HPV-negative OPSCC, respectively.
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Project description:Oropharyngeal cancers have 2 main etiologies : High risk HPV (human papilloma virus) and tobacco/alcohol. The aim of this work is to find a miRNA signature specific to HPV induced oropharyngeal cancers
2015-05-12 | E-MTAB-3410 | biostudies-arrayexpress
Project description:BackgroundIncidence of human papillomavirus (HPV)-related oropharyngeal cancer is increasing. There is interest in identifying healthy individuals most at risk for development of oropharyngeal cancer to inform screening strategies.Patients and methodsAll data are from 2009 to 2014, including 13 089 people ages 20-69 in the National Health and Nutrition Examination Survey (NHANES), oropharyngeal cancer cases from the Surveillance, Epidemiology, and End Results (SEER 18) registries (representing ∼28% of the US population), and oropharyngeal cancer mortality from National Center for Health Statistics (NCHS). Primary study outcomes are (i) prevalence of oncogenic HPV DNA in an oral rinse and gargle sample, and (ii) incident oropharyngeal squamous cell cancer.ResultsOncogenic oral HPV DNA is detected in 3.5% of all adults age 20-69 years; however, the lifetime risk of oropharyngeal cancer is low (37 per 10 000). Among men 50-59 years old, 8.1% have an oncogenic oral HPV infection, 2.1% have an oral HPV16 infection, yet only 0.7% will 'ever' develop oropharyngeal cancer in their lifetime. Oncogenic oral HPV prevalence was higher in men than women, and increased with number of lifetime oral sexual partners and tobacco use. Men who currently smoked and had ≥5 lifetime oral sexual partners had 'elevated risk' (prevalence = 14.9%). Men with only one of these risk factors (i.e. either smoked and had 2-4 partners or did not smoke and had ≥5 partners) had 'medium risk' (7.3%). Regardless of what other risk factors participants had, oncogenic oral HPV prevalence was 'low' among those with only ≤1 lifetime oral sexual partner (women = 0.7% and men = 1.7%).ConclusionsScreening based upon oncogenic oral HPV detection would be challenging. Most groups have low oncogenic oral HPV prevalence. In addition to the large numbers of individuals who would need to be screened to identify prevalent oncogenic oral HPV, the lifetime risk of developing oropharyngeal caner among those with infection remains low.
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Project description:Patients with human papillomavirus- (HPV-) related oropharyngeal squamous cell carcinoma (OPSCC) have a better prognosis than HPV-negative OPSCC when treated with standard high-dose cisplatin-based chemoradiotherapy. Consistent with this assertion and due to younger age at diagnosis, novel approaches to minimize treatment sequelae while preserving survival outcomes become of paramount importance. Here, we critically reviewed the evidence-based literature supporting the deintensification strategies in HPV-related OPSCC management, including radiotherapy dose and/or volume reduction, replacement of cisplatin radiosensitising chemotherapy, and the use of transoral surgery. Undoubtedly, further researches are needed before changing the standard of care in this setting of patients.
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Project description:PurposePlasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence.Methods and materialsA prospective biomarker clinical trial was conducted among patients with nonmetastatic HPV-associated (p16-positive) OPSCC. All patients were treated with curative-intent chemoradiotherapy (CRT). Patients underwent a 3-month post-CRT positron emission tomography/computed tomography scan and were thereafter clinically evaluated every 2-4 months (years 1-2), then every 6 months (years 3-5). Chest imaging was performed every 6 months. Blood specimens were collected every 6-9 months for analysis of plasma ctHPVDNA using a multianalyte digital polymerase chain reaction assay. The primary endpoint was to estimate the negative predictive value (NPV) and positive predictive value (PPV) of ctHPVDNA surveillance.ResultsOne hundred fifteen patients were enrolled, and 1,006 blood samples were analyzed. After a median follow-up time of 23 months (range, 6.1-54.7 months), 15 patients (13%) developed disease recurrence. Eighty-seven patients had undetectable ctHPVDNA at all post-treatment time points, and none developed recurrence (NPV, 100%; 95% CI, 96% to 100%). Twenty-eight patients developed a positive ctHPVDNA during post-treatment surveillance, 15 of whom were diagnosed with biopsy-proven recurrence. Sixteen patients had 2 consecutively positive ctHPVDNA blood tests, 15 of whom developed biopsy-proven recurrence. Two consecutively positive ctHPVDNA blood tests had a PPV of 94% (95% CI, 70% to 99%). Median lead time between ctHPVDNA positivity and biopsy-proven recurrence was 3.9 months (range, 0.37-12.9 months).ConclusionDetection of ctHPVDNA in two consecutive plasma samples during post-treatment surveillance has high PPV and NPV for identifying disease recurrence in patients with HPV-associated oropharyngeal cancer and may facilitate earlier initiation of salvage therapy.
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