Kinetics of the Human Papillomavirus Type 16 E6 Antibody Response Prior to Oropharyngeal Cancer

Kreimer, Aimée R.; Johansson, Mattias; Yanik, Elizabeth L.; Katki, Hormuzd A.; Check, David P.; Kuhs, Krystle A. Lang; Willhauck‐Fleckenstein, Martina; Holzinger, Dana; Hildesheim, Allan; Pfeiffer, Ruth M.; Williams, Craig R.; Freedman, Neal D.; Huang, Wen‐Yi; Purdue, Mark P.; Michel, Angelika; Pawlita, Michael; Brennan, Paul; Waterboer, Tim

doi:10.1093/jnci/djx005

Cited by 84 publications

(134 citation statements)

References 29 publications

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“…8 Using the same multiplex assay, these results were validated in Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) where antibody levels were found to remain elevated and stable for up to 13 years prior to diagnosis. 12 Moreover, the 10-year cumulative incidence of OPC among seropositive individuals 6.2% among men and 1.3% among women. 12 In a previous study of 256 OPC cases and 250 controls, we found that seropositivity for E2, E6, and/or E7 was associated with OPC risk (OR, 249.1; 95% CI, 99.3-624.9).…”

Section: Discussionmentioning

confidence: 99%

“…12 Moreover, the 10-year cumulative incidence of OPC among seropositive individuals 6.2% among men and 1.3% among women. 12 In a previous study of 256 OPC cases and 250 controls, we found that seropositivity for E2, E6, and/or E7 was associated with OPC risk (OR, 249.1; 95% CI, 99.3-624.9). 9 Our current results are consistent with these previous findings.…”

Section: Discussionmentioning

confidence: 99%

“…8,9,12,13,22-24 In data from the European Prospective Investigation Into Cancer and Nutrition cohort, which included 638 patients with head and neck cancer and 1,599 control subjects, antibodies to E6 were present in fewer than 1% of controls and 35% of OPC cases; furthermore, antibodies could be detected more than 10 years before diagnosis. 8 Using the same multiplex assay, these results were validated in Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) where antibody levels were found to remain elevated and stable for up to 13 years prior to diagnosis.…”

Section: Discussionmentioning

confidence: 99%

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Diagnostic accuracy of serum antibodies to human papillomavirus type 16 early antigens in the detection of human papillomavirus–related oropharyngeal cancer

Dahlstrom

Anderson

Field

et al. 2017

Cancer

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Background Given the current epidemic of human papillomavirus (HPV)-related oropharyngeal cancer (OPC), a screening strategy is urgently needed. The presence of serum antibodies to HPV16 early (E) antigens is associated with an increased risk for OPC. The purpose of this study was to evaluate the diagnostic accuracy of antibodies to a panel of HPV16 E antigens in screening for OPC. Methods This case-control study included 378 patients with OPC; 153 patients with non-oropharyngeal head and neck cancer (non-OPC); and 782 healthy control subjects. Tumor HPV status was determined by p16 immunohistochemistry and HPV in situ hybridization. HPV16 E antibody levels in serum were identified by ELISA. A trained binary logistic regression model based on the combination of all E antigens was pre-defined and applied to the dataset. We calculated sensitivity/specificity of the assay to distinguish HPV-related OPC from controls. Logistic regression analysis was used to calculate odds ratios (OR) with 95% confidence intervals (CI) for the association of head and neck cancer with antibody status. Results Of the 378 patients with OPC, 348 had p16-positive OPC. HPV16 E antibody levels were significantly higher among patients with p16-positive OPC but not among patients with non-OPC or among controls. Serology showed high sensitivity and specificity for HPV-related OPC (binary classifier: sensitivity, 83% and specificity, 99% for p16-positive OPC). Conclusions A trained binary classification algorithm that incorporates information about multiple E antibodies showed high sensitivity and specificity and may be advantageous for risk stratification in future screening trials.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Diagnostic accuracy of serum antibodies to human papillomavirus type 16 early antigens in the detection of human papillomavirus–related oropharyngeal cancer

Dahlstrom

Anderson

Field

et al. 2017

Cancer

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“…This analysis projects noteworthy incidence rates of OPC in HPVunvaccinated US white men over the coming decades ( Fig. 17,18 The detection of HPV in oral samples may be attractive as a research tool because noninvasive mouthwash and gargle specimens are simple to obtain. 1).…”

Section: Incidence and Survival Rates For Opcmentioning

confidence: 97%

Screening for human papillomavirus‐driven oropharyngeal cancer: Considerations for feasibility and strategies for research

Kreimer

Shiels

Fakhry

et al. 2018

Cancer

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INTRODUCTIONOver the past 25 years, human papillomavirus (HPV) has been shown to be an important cause of oropharyngeal cancers (OPCs) in many world regions, with the great majority of HPV-driven OPC being caused by HPV type 16 (HPV-16). 1 HPV currently is overtaking tobacco exposure as the leading cause of OPC in some countries with a high human development index, including the United States and some European and Latin American countries, in which both the incidence rate of OPC and the attributable fraction (AF) of HPV are rising. 2 In the United States, the incidence of OPC currently is greater than that of cervical cancer, a consequence of the increasing incidence of OPC as well as reductions in the incidence of cervical cancer due to the success achieved by screening. 3 This shift highlights the need for parallel preventive measures. Nevertheless, arguments against additional research regarding HPV-driven OPC screening have been made and include the promise of primary prevention through HPV vaccination, 4 the currently low incidence rates, 5 and favorable outcomes with current therapy compared with non-HPV-driven head and neck cancers. 6 The lack of an identifiable clinical precursor lesion, insufficient diagnostic technology with which to detect small lesions, and the absence of de-escalated clinical management for patients with early-stage cancer or precancer are current barriers to screening for OPC. This article is not intended to address all the questions related to the validity and timeliness of screening for HPV-driven OPC but instead to raise important questions, guide discussions, highlight deficits and/or confusion in the existing literature, and propose needed steps in the research agenda. The following general aspects of a screening program are considered 7 and applied to HPV-driven OPC: 1) a sufficiently high incidence, either in the general population or an enriched high-risk population; 2) a sensitive and specific screening tool or biomarker; 3) appropriate methods for accurately diagnosing the cancer (or precancer) among individuals who screen positive; 4) effective treatment for patients with early-stage lesions; and 5) evidence of mortality and/or morbidity reductions.

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“…Viral integration in the host cells and additional risk factors including a twisted T-cell homeostasis might support HPV persistence in the tonsils which over time eventually leads to HPV-associated OPSCC. This could also neatly explain why high titers of HPV16 E6 antibodies have been shown to predict the development of incident HPV-driven OPSCC even 10–15 years in advance [79, 104]. …”

Section: The New Hypothesismentioning

confidence: 99%

HPV in Head and Neck Carcinomas: Different HPV Profiles in Oropharyngeal Carcinomas – Why?

Syrjänen

2019

Acta Cytologica

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Background: The association of human papillomavirus (HPV) with head and neck squamous cell carcinoma (HNSCC) was first described in 1982–1983 by the authors of this review. Prompted by this discovery 35 years ago, an entirely new field of HPV research has emerged, resulting in a paradigm shift from smoking and alcohol as the only etiological factors to confirmation of HNSCC as an important group of HPV-related human malignancies. Summary: In this review, the authors first describe the scope (i.e., HNSCC) by the anatomic sites of the tumors. Their important site-specific differences in epidemiology are emphasized, and the misconceptions caused by the adopted practice of pooling all tumors from these divergent anatomic sites as a single entity (HNSCC) are pinpointed. The convincing evidence of the established risk factors (smoking and alcohol) is briefly addressed, before entering in the discussion on the causal role of HPV in HNSCC pathogenesis. The global HPV prevalence in different subsets of HNSCC is summarized using the data extracted from all meta-analyses published since 2010. Of all HNSCC subsets, oropharyngeal SCC has an HPV profile distinct form all the other subsets, and the possible mechanisms explaining this intimate association with HPV are discussed. Key Messages: Recent global trends show a constant increase in HNSCC rates particularly among younger age groups. The evidence on cigarette smoking and alcohol consumption as the prime risk factors of HNSCC is overwhelming. During the past 35 years, however, increasing evidence has accumulated implicating an important causal role of HPV in HNSCC. These data have important clinical implications, HPV detection and tailored treatment strategies for HPV-positive HNSCCs currently being an integral part of the oncological management practices of HNSCC.

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Kinetics of the Human Papillomavirus Type 16 E6 Antibody Response Prior to Oropharyngeal Cancer

Cited by 84 publications

References 29 publications

Diagnostic accuracy of serum antibodies to human papillomavirus type 16 early antigens in the detection of human papillomavirus–related oropharyngeal cancer

Diagnostic accuracy of serum antibodies to human papillomavirus type 16 early antigens in the detection of human papillomavirus–related oropharyngeal cancer

Screening for human papillomavirus‐driven oropharyngeal cancer: Considerations for feasibility and strategies for research

HPV in Head and Neck Carcinomas: Different HPV Profiles in Oropharyngeal Carcinomas – Why?

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