Human Papillomavirus Oropharyngeal Cancer Research Articles

Hypothesis of a CD137/Eomes activating axis for effector T cells in HPV oropharyngeal cancers

Chronic Human Papilloma Virus (HPV) infection is supplanting alcohol and tobacco intoxications as the leading cause of oropharyngeal cancer in developed countries. HPV-related squamous cell carcinomas of the oropharynx (HPV + OSC) present better survival and respond better to radiotherapy and chemotherapy. Regulatory T cells (TREG) are mainly described as immunosuppressive and protumoral in most solid cancers. However, TREG are paradoxically associated with a better prognosis in HPV + OSCs. The transcription factor FoxP3 is the basis for the identification of TREG. Among CD4 + FoxP3 + T cells, some have effector functions. A medical hypothesis is formulated here: the existence of a CD137 (4.1BB)-Eomesodermin (Eomes) activated pathway downstream of TCR-specific activation in a subpopulation of CD4 + FoxP3 + T cells may explain this effector function. Evidence suggest that this axis may exist either in CD4 + FoxP3 + T cells or CD8 + T cells. This pathway could lead T cells to strong antitumor cytotoxic activity in a tumor-specific manner. Furthermore, CD137 is one of the most expected targets for the development of agonist immunotherapies. The identification of CD137 + Eomes + FoxP3+/- T cells could be a key element in the selective activation of the most anti-tumor cells in the HPV + OSC microenvironment.

Importance of lymph node ratio in HPV-related oropharyngeal cancer patients treated with surgery and adjuvant treatment.

ObjectivesThe pathologic nodal stage of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) patients is classified according to the number of lymph nodes (LNs), as revised in 2018. Previous studies showed that the LN ratio (LNR) could be also a significant prognostic factor in head and neck cancer, but there are few studies on the LNR in HPV-related [HPV(+)] OPC. The aim of the present study was to analyze the predictive value of the LNR for survival and recurrence in HPV(+) OPC patients.Materials and methodsHPV(+) OPC patients treated with surgery with or without postoperative radiotherapy from January 2000 to March 2019 were evaluated. The patients were divided into two sets of three groups, according to LN numbers based on pathologic nodal stages, and LNRs by a cutoff value of 0.05. The medical records were reviewed, and the overall survival (OS), disease-free survival, locoregional recurrence, and distant metastasis incidence were analyzed.ResultsNinty patients were included and the median follow-up period was 38.2 months. There were no significant differences in OS in the LN number groups. However, there was a significant difference in OS in the LNR groups (P = 0.010). The incidence of distant metastasis in the LNR groups was significantly different (P = 0.005).ConclusionThe LNR in HPV(+) OPC patients may be a more useful tool to predict survival and distant metastasis than the LN number. Additional research and consensus on surgical pathology are needed before applying the LNR to adjuvant treatment decisions and pathologic nodal staging.

More than cervical cancer: Understanding racial/ethnic disparities in oropharyngeal cancer outcomes among males by HPV status.

Context: Over the last two decades the incidence of male oropharyngeal cancers (OPCa) has increased rapidly in the United States, yet OPCa is mostly preventable. Differences in OPCa incidence and outcomes by race/ethnicity and human papillomavirus (HPV) status have not been previously studied. Objective: Examine racial/ethnic disparities in HPV-related and non-HPV related OPCa outcomes among males. Study Design: Nationwide population-based retrospective cohort study. Setting or Dataset: North American Association of Central Cancer Registries' Cancer in North America Deluxe dataset, covering 93% of the U.S. population. Population studied: Males diagnosed with OPCa in the U.S. between January 2005 and December 2016 (N=175,843). Outcome Measures: OPCa incidence rates by race/ethnicity [Non-Hispanic White, Non-Hispanic Black, Hispanic, Non-Hispanic Other] and HPV status (HPV-related or non-HPV-related); late-stage diagnosis; mean and cumulative survival; cancer-specific mortality. Results: Most male OPCa were HPV-related (92.2%) and in Whites (83.6%), with over 50% increase from 2005 to 2016 in age-adjusted incidence of late-stage HPV-related OPCa among Whites. There was no difference in late-stage diagnosis between Whites and Blacks (aOR, 0.99, 95% CI, 0.94-1.05) or Hispanics (aOR, 0.96, 95% CI, 0.89-1.03), while Other race had 15% lower odds of late-stage diagnosis (95% CI, 0.79-0.95). Independent predictors of late-stage disease included having Medicaid (aOR, 1.37, 95% CI, 1.28-1.46) or no insurance (aOR, 1.44, 95% CI, 1.32-1.57) and HPV-related OPCa (aOR, 3.53, 95% CI, 3.37-3.70). Lower mean survival in HPV-related OPCa compared with Whites (99.63 months, 95% CI, 99.18-100.07) was seen among Blacks (69.72 months, 95% CI, 68.14-71.31) and Hispanics (91.89 months, 95% CI, 89.87-93.91; p < 0.01). Blacks had lowest adjusted cumulative survival for HPV and non-HPV related OPCa (p<0.001). Blacks (aHR, 1.78, 95% CI, 1.70-1.87), Hispanics (aHR, 1.11, 95% CI, 1.03-1.19), and HPV-related OPCa (aHR, 1.25, 95% CI, 1.17-1.34) had higher cancer-specific mortality. Adjusting for treatment eliminated the higher mortality among Hispanics, but not in Blacks. Conclusions: To decrease incidence rates of late stage OPCa, HPV vaccination and possibly, HPV OPCa screening should be advocated, especially in White males. Further research to explicate possible biologic mechanisms and behaviors or comorbidities contributing to the higher OPCa mortality among Black males is needed.

The impact of Human Papilloma Virus status on the prediction of head and neck cancer chemoradiotherapy outcomes using the pre-treatment apparent diffusion coefficient.

Objective:To determine the impact of Human Papilloma Virus (HPV) oropharyngeal cancer (OPC) status on the prediction of head and neck squamous cell cancer (HNSCC) chemoradiotherapy (CRT) outcomes with pre-treatment quantitative diffusion-weighted magnetic resonance imaging (DW-MRI).Methods:Following ethical approval, 65 participants (53 male, age 59.9 ± 7.86) underwent pre-treatment DW-MRI in this prospective cohort observational study. There were 46 HPV OPC and 19 other HNSCC cases with Stage III/IV HNSCC. Regions of interest (ROIs) (volume, largest area, core) at the primary tumour (n = 57) and largest pathological node (n = 59) were placed to analyse ADCmean and ADCmin. Unpaired t-test or Mann–Whitney test evaluated the impact of HPV OPC status and clinical parameters on their prediction of post-CRT 2 year locoregional and disease-free survival (LRFS and DFS). Multivariate logistic regression compared significant variables with 2 year outcomes.Results:On univariate analysis of all participants, the primary tumour area ADCmean was predictive of 2 year LRFS (p = 0.04). However, only the HPV OPC diagnosis (LFRS p = 0.03; DFS p = 0.02) predicted outcomes on multivariate analysis. None of the pre-treatment ADC values were predictive of 2 year DFS in the HPV OPC subgroup (p = 0.21–0.68). Amongst participants without 2 year disease-free survival, HPV-OPC was found to have much lower primary tumour ADCmean values than other HNSCC.Conclusion:Knowledge of HPV OPC status is required in order to determine the impact of the pre-treatment ADC values on post-CRT outcomes in HNSCC.Advances in knowledge:Pre-treatment ADCmean and ADCmin values acquired using different ROI methods are not predictive of 2 year survival outcomes in HPV OPC.

Extrachromosomal DNA in HPV-Mediated Oropharyngeal Cancer Drives Diverse Oncogene Transcription.

Human papillomavirus (HPV) plays a major role in oncogenesis and circular extrachromosomal DNA (ecDNA) is found in many cancers. However, the relationship between HPV and circular ecDNA in human cancer is not understood. Forty-four primary tumor tissue samples were obtained from a cohort of patients with HPV-positive oropharynx squamous cell carcinoma (OPSCC). Twenty-eight additional HPV oropharyngeal cancer (HPVOPC) tumors from The Cancer Genome Atlas (TCGA) project were analyzed as a separate validation cohort. Genomic, transcriptomic, proteomic, computational, and functional analyses of HPVOPC were applied to these datasets. Our analysis revealed circular, oncogenic DNA in nearly all HPVOPC, with circular human and human-viral hybrid ecDNA present in over a third of HPVOPC and viral circular DNA in remaining tumors. Hybrid ecDNA highly express fusion transcripts from HPV promoters and HPV oncogenes linked to downstream human transcripts that drive oncogenic transformation and immune evasion, and splice multiple, diverse human acceptors to a canonical SA880 viral donor site. HPVOPC have high E6*I expression with specific viral oncogene expression pattern related to viral or hybrid ecDNA composition. Nonchromosomal circular oncogenic DNA is a dominant feature of HPVOPC, revealing an unanticipated link between HPV and ecDNA that leverages the power of extrachromosomal inheritance to drive HPV and somatic oncogene expression.

Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer

Although several oropharyngeal cancer (OPC) susceptibility loci have been identified, most previous studies lacked detailed information on human papillomavirus (HPV) status. We conduct a genome-wide analysis by HPV16 serology status in 4,002 oral cancer cases (OPC and oral cavity cancer (OCC)) and 5,256 controls. We detect four susceptibility loci pointing to a distinct genetic predisposition by HPV status. Our most notable finding in the HLA region, that is now confirmed to be specific of HPV(+)OPC risk, reveal two independent loci with strong protective effects, one refining the previously reported HLA class II haplotype association. Antibody levels against HPV16 viral proteins strongly implicate the protective HLA variants as major determinants of humoral response against L1 capsid protein or E6 oncoprotein suggesting a natural immune response against HPV(+)OPC promoted by HLA variants. This indicates that therapeutic vaccines that target E6 and attenuate viral response after established HPV infections might protect against HPV(+)OPC.

Should the HPV positive oropharyngeal cancer patient be considered for a two-stage dental assessment for their radiation treatment?

Patients due to commence head and neck radiation treatment are expected to undergo a dental assessment and be deemed ‘dentally fit’. Though this intervention is welcomed by the dental fraternity it is not without its challenges especially in human papilloma virus (HPV) related oropharyngeal cancer (OPC) which has seen a phenomenal rise over the past decade. This perspective piece presents these challenges and proposes a potential adaption of the dental assessment for HPV OPC patients though not necessarily exclusive to this tumour sub-site.

Therapeutic strategies:Surgery for human papillomavirus-associated oropharyngeal carcinoma.

Treatment of oropharyngeal cancer (OPC) has undergone considerable evolution since the discovery of human papillomavirus (HPV)-associated OPC. It is widely understood that HPV OPC affects a younger population and standard treatment offers improved oncologic outcomes compared with non-HPV OPC but can cause significant toxicities and long-term side effects. Surgery for treatment de-escalation is an active area of research. The purpose of this review is to explore surgery as it relates to the treatment of HPV OPC with a focus on the evolution of treatment, rationale for surgery, surgical techniques, outcomes, and the role of surgery in de-escalation of treatment.

Epidemiology and incidence of HPV-related cancers of the head and neck.

Globally, 4.5% of cancers are due to the human papillomavirus (HPV). In the United States, 80 million people are infected with HPV, and the incidence of HPV oropharyngeal cancer has surpassed HPV cervical cancer. The highest burden of oropharyngeal cancer is seen in middle-aged and increasingly older White men. HPV vaccination promises to change the epidemiology of this disease, but HPV vaccination rates remain too low today to reduce disease transmission.

The ability of post-chemoradiotherapy DWI ADCmean and 18F-FDG SUVmax to predict treatment outcomes in head and neck cancer: impact of human papilloma virus oropharyngeal cancer status

ObjectivesTo evaluate the ability of post-chemo-radiotherapy (CRT) diffusion-weighted-MRI apparent diffusion coefficient (ADCmean) and 18F-FDG PET maximum standardized uptake value (SUVmax) to predict disease-free survival (DFS) in head and neck squamous cell carcinoma (HNSCC), and to determine whether this ability is influenced by human papillomavirus oropharyngeal cancer (HPV-OPC) status.MethodsThis prospective cohort observational study included 65 participants (53 male, mean ± SD age 59.9 ± 7.9 years, 46 HPV-OPC) with stage III or IV HNSCC. Primary tumour and nodal ADCmean (pre-treatment, 6- and 12-weeks post-CRT) and SUVmax (12-weeks post-CRT) were measured. Variables were compared with 2-year DFS (independent t-test/Mann–Whitney test) and overall DFS (Cox regression), before and after accounting for HPV-OPC status. Variables were also compared between HPV-OPC and other HNSCC subgroups after stratifying for DFS.ResultsAbsolute post-CRT ADCmean values predicted 2-year DFS and overall DFS for all participants (p = 0.03/0.03, 6-week node; p = 0.02/0.03 12-week primary tumour) but not in the HPV-OPC subgroup. In participants with DFS, percentage interval changes in primary tumour ADCmean at 6- and 12-weeks were higher in HPV-OPC than other HNSCC (p = 0.01, 6 weeks; p = 0.005, 12 weeks). The 12-week post-CRT SUVmax did not predict DFS.ConclusionAbsolute post-CRT ADCmean values predicted DFS in HNSCC but not in the HPV-OPC subgroup. Amongst participants with DFS, post-CRT percentage interval changes in primary tumour ADCmean were significantly higher in HPV-OPC than in other HNSCC. Knowledge of HPV-OPC status is crucial to the clinical utilisation of post-CRT DWI-MRI for the prediction of outcomes.

Insurance Status as a Predictor of Treatment in Human Papillomavirus Positive Oropharyngeal Cancer.

The link between human papillomavirus (HPV) and oropharyngeal cancer (OPC) is well known. Locally advanced, HPV-positive OPC (HPV OPC) can be treated with either chemoradiation or primary surgery with or without adjuvant therapy. Head and neck cancer patients with government insurance or uninsured have been shown to have worse prognosis than similar patients with private insurance. In this study, we aimed to determine if insurance status would predict treatment modality in patients with HPV OPC. A retrospective analysis using the National Cancer Database (NCDB). The National Cancer Database was used to identify patients with HPV OPC who underwent primary surgery or primary chemoradiation from 2010-2015. Insurance status was categorized as government, private, or no insurance. The relationship between insurance status and treatment was investigated using Chi square and multivariate regression models. Kaplan-Meier analyses were performed comparing overall survival (OS) by insurance status. There were 10,606 patients were included. There was a statistically significant correlation between insurance status and primary treatment modality for HPV OPC (P < .001). Patients with government insurance were 19.3% less likely to undergo surgery and uninsured patients were 36.9% less likely to undergo primary surgery when compared to those with private insurance (P < .001), even after correcting for TNM stage in multivariate analysis. There was an improved 5-year OS for patients with private insurance (86.6%) versus both government insurance (68.4%) and no insurance (69.9%) (P < .001). Patients with private insurance are more likely to undergo primary surgery in HPV OPC and have improved overall survival. 4 Laryngoscope, 131:776-781, 2021.

'Good cancer gone bad': a narrative review of HPV oropharyngeal cancer and potential poor outcomes.

Oropharyngeal cancer (OPC) remains a significant health burden and about 15-30% of these have been attributed to the human papillomavirus (HPV). Human papillomavirus-related oropharyngeal cancer (HPV OPC) includes tumours which are detected to be p16INK4A positive or have the HPV DNA detected by in situ hybridisation or polymerase chain reaction. HPV OPC is generally believed to have a relatively good prognosis. More recently, there is a recognised pattern of atypical spread in a highly aggressive subset of HPV OPC. These are HPV OPCs which develop distant metastasis or recurrence. This review raises awareness of this subset of HPV OPC and factors associated with poor outcomes. A review of the literature available on HPV OPC was carried out. Studies were sourced from PubMed with searching of relevant headings and sub-headings and cross-referencing. Factors associated with highly aggressive HPV OPC include nodal stage and nodal morphology, alcohol and tobacco use, age and biological characteristics. Treatment options in cases of disease recurrence include salvage resection radiotherapy and/or chemotherapy and management options vary depending on the nature of recurrence and initial treatment. Recent updates in HPV OPC staging have made staging and treatment of tumours more accurate. While HPV OPC overall carries a relatively good prognosis, it is important for clinicians to be aware of potentially highly aggressive cases of HPV OPC and to be aware of factors that should prompt close monitoring.

US oral health students' willingness to train and administer the HPV vaccine in dental practices.

HPV oropharyngeal cancers have now surpassed cervical cancer rates in the US. Dental providers' engagement in HPV education and vaccination efforts may help reduce the burden of HPV oropharyngeal cancers. We examined factors associated with oral health students' willingness to train and administer the human papillomavirus (HPV) vaccine in dental settings. US students in 15 oral health programs participated in an online survey in 2016. Unadjusted and adjusted multivariable logistic regression were conducted and odds ratios (OR) and 95% confidence intervals (CI) were reported. Analyses were conducted in SAS Version 9.4. Data from a total of N = 306 students were analyzed to examine sociodemographic, educational, practice, and attitudinal factors associated with willingness to train and administer the HPV vaccine. Majority of the participants were female (70.3%), non-Hispanic/Latino (90.8%), and White (62.1%). Perceiving that HPV vaccination recommendation (OR = 1.95, 95% CI = 1.14–3.35) and administration (OR = 3.79, 95% CI = 1.63–8.81) was in the dental professional's scope was positively associated with outcome measures when other factors were held constant. Students with greater patient contact time (OR = 4.47, 95% CI = 1.14–17.58) and lower role conflict (agreed that HPV vaccine administration was in the dental professional's scope) had higher odds of willingness to administer the HPV vaccine when other factors were held constant (OR = 5.9, 95% CI = 2.27–15.3). The major barrier to engaging oral health students in HPV vaccination efforts was role conflict. Professional organizations and oral health programs should strongly support the role of oral health professionals in HPV oropharyngeal prevention.

Management of Oropharyngeal Cancer in the HPV Era.

Historically, oropharyngeal cancer (OPC) has been attributed to risk factors such as smoking and alcohol use. The increased incidence of OPC has been driven by human papillomavirus (HPV) infection. A search of the literature involving HPV infection and OPC was performed, along with a search of ongoing clinical trials regarding HPV-positive OPC. This review summarizes the differences in epidemiology and prognosis of HPV-positive OPC compared with non-HPV-related OPC. It will also discuss use of de-escalating treatment to minimize toxicity while maintaining excellent outcomes. Disease management is also addressed, including prevention and follow-up recommendations for this cohort of patients. HPV-positive OPC is a distinct disease, and efforts should be made to personalize its management. Preventive measures and vaccinations, along with de-escalation of treatment, may help optimize outcomes in this population.

Strategy of Using Intratreatment Hypoxia Imaging to Selectively and Safely Guide Radiation Dose De-escalation Concurrent With Chemotherapy for Locoregionally Advanced Human Papillomavirus–Related Oropharyngeal Carcinoma

Toreport a small substudy of an ongoing large, multi-arm study using functional imaging to assess pre-/intratreatment hypoxia for all head and neck cancer, in which we hypothesized that pre- and early-treatment hypoxia assessment using functional positron emission tomography (PET) imaging may help select which human papillomavirus (HPV)-positive (HPV(+)) oropharyngeal cancer (OPC) patients can safely receive radiation de-escalation without jeopardizing treatment outcomes. Patients with HPV(+) oropharyngeal carcinoma were enrolled on an institutional review board-approved prospective study of which de-escalation based on imaging response was done for node(s) only. Pretreatment (18)F-fluorodeoxyglucose and dynamic (18)F-FMISO (fluoromisonidazole) positron emission tomography (PET) scans were performed. For patients with pretreatment hypoxia on(18)F-FMISO PET (defined as a >1.2 tumor to muscle standard uptake value ratio), a repeat scan was done 1week after chemoradiation. Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10-Gy dose reduction to metastatic lymph node(s). The 2-year local, regional, distant metastasis-free, and overall survival rates were estimated using the Kaplan-Meier product-limit method. A subset of patients had biopsy of a hypoxic node done under image guidance. Thirty-three HPV(+) OPC patients were enrolled in this pilot study. One hundred percent showed pretreatment hypoxia (at primary site and/or node[s]), and among these, 48% resolved (at primary site and/or node[s]); 30% met criteria and received 10-Gy reduction to the lymph node(s). At the median follow-up of 32months (range, 21-61months), the 2-year locoregional control rate was 100%. One patient failed distantly with persistence of hypoxia on (18)F-FMISO PET. The 2-year distant metastasis-free ratewas 97%. The 2-year OS rate was 100%. Hypoxia on imaging was confirmed pathologically. Hypoxia is present in HPV(+) tumors but resolves within 1week of treatment in 48% of cases either at the primary site and/or lymph node(s). Our 100% locoregional control rate suggests that intratreatment functional imaging used to selectively de-escalate node(s) to 60Gy was confirmed safe using our stringent imaging criteria. Intratreatment functional imaging warrants further study to determine its ultimate role in de-escalation treatment strategies.

The Expression of P53, &amp;Bgr;-Tubulin, Bcl-2 According to P16 Status in Advanced Oropharyngeal Cancer After Induction Chemotherapy Followed By Concurrent Chemoradiotherapy

ABSTRACT Aim: Oropharyngeal cancer (OPC) associated with human papilloma virus (HPV) shows better treatment outcomes than non-HPV OPC. We investigated the expression of p53, b-tubulin, bcl-2 and ERCC 1 according to p16 status in OPC patients receiving induction chemotherapy followed by concurrent chemoradiotherapy. Methods: Patients who were treated with at least 2 cycles of induction chemotherapy for locally advanced oropharyngeal cancer from 2004 to 2011 were reviewed. Immunohistochemical staining of p53, b-tubulin, bcl-2, ERCC, which are well known to be associated with chemotherapy response, and p16, as a surrogate marker for HPV, was done in paraffin-embedded tumor tissue. We analyzed the response for chemotherapy and survival outcomes according to p16 expression. Results: Seventy-four patients were enrolled for this study. All patients received induction chemotherapy with docetaxel, 5-FU, cisplatin (n = 72) or 5-FU and cisplatin (n = 2). One patient received a salvage operation and eight patients were not given radiotherapy due to poor general condition after induction chemotherapy. Therefore, 65 patients received chemoradiotherapy subsequently (total radiation dose; ≥60Gy n = 54, Conclusions: OPC associated with HPV (HPV OPC) showed lower expression of p53, beta tubulin and higher expression of bcl-2 than non-HPV OPC. In addition, the expressions of p53 and beta tubulin were prognostic factors for OPC. This result suggested the underlying mechanism of better response to chemotherapy in case of HPV OPC than non-HPV OPC and de-escalation of treatment in patients with HPV OPC could be considered based on clinical trial results. Disclosure: All authors have declared no conflicts of interest.

The New Cancer Patient: Young, Non‐smoker, HPV+: Evaluation

Program Description: The near-epidemic rise of the incidence of human papillomavirus (HPV)-related oropharyngeal carcinomas presents the practitioner with a “new” head and neck cancer patient, vastly different from those with the traditional risk factors who formed the basis of our training experience. Accordingly, a thorough and disease-specific evaluation process is necessitated. Using a case-based format and the following presentations from experts in the field, this miniseminar will review the evaluation of the HPV-related cancer patient: The HPV oropharyngeal cancer epidemic: surgeon’s perspective, role of imaging, evaluation of the neck mass, evaluation of the primary questions every patient wants to ask. Educational Objectives: 1) Recognize the key clinical, epidemiological and pathologic features differentiating HPV-positive oropharyngeal cancer from cancers related to traditional risk factors. 2) Implement a consistent, efficient, and evidence-based evaluation process for the increasing number of patients presenting with oropharyngeal cancers that may be HPV related. 3) Acknowledge and prepare for patient questions related to the viral etiology of HPV-positive oropharyngeal cancer.

PP093: Human papilloma virus oropharyngeal cancer – A review of our current understanding of the anatomic origin of disease, premalignant lesions and persistence of oral HPV infection

Purpose There remain significant gaps in our knowledge of HPV oropharyngeal cancer. This review focuses on the available literature on tumour origin, premalignant lesions and persistence of oral HPV infection. Materials and methods Literature search (English literature) of databases AMED, MEDLINE, EMBASE, BNI, PsychINFO (1985–present). Keywords used were human papilloma virus, oropharyngeal cancer, tonsil, tongue base tumours. Results Tumour origin and premalignancy: The anatomic origin of HPV-OPC is unknown. Some studies have suggested the tonsillar crypts as the site where carcinogenesis commences. Kim et al. (2007) showed HPV integration begins in the tonsillar crypts and leads to the alteration of p16, EGFR and c-myc during tumourigenesis. Most tonsil cancers associated with HPV arose from the tonsillar crypts, and tended to be inverted and poorly differentiated. P16 expression localizes to HPV-positive cancers, and has been found to be intrinsic to the specialized epithelium of the tonsillar crypts (Begum et al., 2005). There was no literature confirming the presence of a premalignant state but there are on-going studies. Such identification could allow the development of screening strategies. Persistence Rautava et al. (2012) undertook a prospective Finnish study in 324 pregnant women followed up for 6 years. Oral scrapings were taken with a brush and HPV-genotyping was performed with nested PCR and Multimetrix® test (Progen, Heidelberg, Germany). Seventy-four women had persistent oropharyngeal HPV infection, with HPV 16 and HPV 6 the most frequent types to persist. Persistence was determined as at least two consecutive samples positive with the same HPV genotype. The use of oropharyngeal contraceptives and a second pregnancy were found to be protective against oropharyngeal HPV persistence. Conclusion The tonsil crypts have been suggested as the possible origin of tumour development and HPV 16 and 6 seem to be the most frequent viral strains to persist. Further exploratory studies are required.

Abstract B13: High-risk human papillomavirus prevalence in oral and oropharyngeal premalignant lesions: A critical literature review

Abstract Introduction: During the past decade, there has been a significant increase in the incidence of human papillomavirus (HPV) related squamous cell cancer of the oropharynx, especially those of the tonsil and tongue base. HPV-16 and HPV-18 have been linked to these malignant neoplasms. Generally, oral epithelium undergoes a sequence of histopathological pre-malignant transformations before the development of invasive carcinoma. A study evaluating the prevalence of HPV-16/18 types in histopathologically diagnosed oral pre-malignant lesions (OPL) is lacking. Therefore, we conducted a comprehensive literature review to estimate the prevalence of HR HPV types in different grades of OPLs. Study Design: A critical literature search was conducted using Pubmed and SCOPUS databases for the key terms human papillomavirus infection, head and neck cancer, oral cancer, oral hyperplasia, oral dysplasia, and oral leukoplakia. A total of 90 articles related to HPV in oral tissue and pre-malignant lesions were identified. Of these, 29 articles evaluated the prevalence of HPV in histopathological OPLs (hyperplasia and dysplasia). In addition, 11 out of these 29 articles determined the prevalence of HPV in histologically evaluated leukoplakic samples. Only research articles published from 1990 — 2009 were used for this review. Results: Overall, the 29 articles evaluated high-risk (HR) HPV in 1,171 OPLs. This included 140 hyperplasias, 467 dysplasias, 425 leukoplakic lesions without dysplasia, and 139 leukoplakic lesions with dysplasia. The prevalence of any type of HPV in hyperplasia, dysplasia, leukoplakia without dysplasia, and leukoplakia with dysplasia was 24%, 25%, 28%, and 20% respectively. The prevalence of HR HPV-16/18 in these lesions was 24%, 21%, 26% and 26% respectively. The difference in prevalence of different grades of OPLs was not statistically significant. The prevalence of any HPV type in mild, moderate, and severe dysplastic lesions was 43%, 39%, and 33% respectively. The prevalence of HR HPV-16/18 in mild, moderate, and severe dysplastic lesions was 39%, 32%, and 28% respectively. Conclusion: High-risk HPV infection has been noted even in early stage histopathological OPLs like hyperplasias and mild dysplasias, and their prevalence rate is very similar to high grade OPLs, and oral (OC) and oropharyngeal cancers (OPC). Larger studies are needed to obtain a more precise estimate of the prevalence and persistence of HR HPV in histopathologically diagnosed OPLs in order to better understand the etiopathogenesis of HPV related OC and OPC. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B13.