HPV-related Head And Neck Cancer Research Articles

Awareness of the Link Between Human Papilloma Virus Infection and Head and Neck Cancer Among the General Population and Practitioners: A Literature Review.

Background: Human papilloma virus (HPV) infection is responsible for 4.5% of cancers worldwide, i.e., for around 630,000 new cases per year. Around 38,000 cases per year of HPV-related cancers arise in the head and neck region, of which 21,000 cases are oropharyngeal squamous cell carcinomas (OPSCCs), with an increasing frequency in high-income countries. In our work, we aimed to collect the available evidence about the awareness of the relation between HPV infection and head and neck cancer among patients and practitioners. Methods: This review was based on all available prospective and retrospective studies, case reports, and review articles published up to May 2024 in PubMed. The search keywords used included "human papilloma virus" plus "head and neck cancer", "awareness", "infection", "vaccination", "awareness in patients and practitioners", "oropharyngeal squamous cell carcinoma", "HPV16-18", "HPV awareness", "cervical cancer". Results: In the U.S.A., with more than 150.00 participants interviewed through different studies, the identification of HPV infection as a risk factor for head and neck cancer (HNC) was made by only 12-39% of the participants. Similar conclusions were drawn from European studies in which only 10-52% of the participants recognized HPV as a risk factor for HNC. HPV-related HNC awareness in health care providers and medical/dental students showed a high variability among studies, being otolaryngology and dental sciences specialists the most conscious in comparison to general practitioners, who demonstrated a low level of awareness. Conclusions: There is a dangerous lack of awareness about HPV infection and its potential role in HNC among both general populations and health care practitioners. A great effort should be made to increase awareness in both practitioners and the general population on this topic, also aiming to increase the HPV vaccination coverage.

A retrospective chart review of palliative care consultation during curative-intent chemoradiation for head and neck cancer.

e24165 Background: Head and neck cancer (HNC) treatment with chemoradiation therapy (CRT) is highly morbid. Patients develop significant symptoms including severe pain, dysphagia, and malnutrition resulting in poor quality of life (QOL), frequent hospitalizations, and high rates of depression. Although integration of palliative care (PC) teams into the care of incurable cancers has resulted in improved QOL, less is known about its integration into the care of patients receiving curative-intent treatments. We sought to characterize the use of PC during HNC CRT at a single cancer center. Methods: We performed a retrospective chart review of patients who received curative-intent CRT for HNC from 1/2008 to 1/2019 at Fox Chase Cancer Center. We excluded patients with metastatic disease or who participated in a PC intervention study. Data extracted included: demographics, comorbidities, cancer subtypes, human papilloma virus (HPV) status, inpatient admissions, feeding tube use, pain medication usage, and PC referrals throughout CRT. We used parametric and non-parametric statistics for hypothesis testing. Results: A total of 332 patients were included; median age was 60, 73% were male, 57.8% had oropharynx HNC, 10.2% had a history of chronic pain, and 18.9% had a psychiatric diagnosis. At the start of treatment, 38.5% of patients were on opioids for cancer pain or chronic pain, which increased to 90.7% of patients by the end of CRT. Six months after CRT, 30% of patients remained on opioids. 44.7% of patients required a feeding tube and 51.4% were admitted to the hospital. Despite the significant symptomatology, only 64 patients (19.2%) were referred to PC during treatment. The patients referred to PC were more likely to be younger (p=0.002), have an inpatient admission during treatment (p=0.001), a history of a psychiatric disorder (p=0.001) or substance abuse (p=0.003), and less likely to have HPV-related HNC. Conclusions: A large majority of patients receiving CRT for HNC faced significant pain with a high hospitalization rate, yet few had the expertise of PC involved in their care. Those who were referred to PC were more likely to have pre-existing substance use or chronic pain. These data provide strong rationale for the development of standardized, PC-based interventions to help with the symptomatology of HNC treatment to better serve this high needs population. [Table: see text]

Identification of p53-target genes in human papillomavirus-associated head and neck cancer by integrative bioinformatics analysis.

Head and neck cancer (HNC) is a highly prevalent and heterogeneous malignancy. Although extensive efforts have been made to advance its treatment, the prognosis remained poor with increased mortality. Human papillomaviruses (HPV) have been associated with high risk in HNC. TP53, a tumor suppressor, is the most frequently altered gene in HNC, therefore, investigating its target genes for the identification of novel biomarkers or therapeutic targets in HPV-related HNC progression is highly recommended. Transcriptomic profiles from three independent gene expression omnibus (GEO) datasets, including 44 HPV+ and 70 HPV- HNC patients, were subjected to integrative statistical and Bioinformatics analyses. For the top-selected marker, further in-silico validation in TCGA and GTEx databases and experimental validation in 65 (51 HPV- and 14 HPV+) subjects with histologically confirmed head and neck squamous cell carcinoma (HNSCC) have been performed. A total of 498 differentially expressed genes (DEGs) were identified including 291 up-regulated genes and 207 down-regulated genes in HPV+ compared to HPV- HNSCC patients. Functional annotations and gene set enrichment analysis (GSEA) showed that the up-regulated genes were significantly involved in p53-related pathways. The integrative analysis between the Hub-genes identified in the complex protein-protein network and the top frequent genes resulting from GSEA showed an intriguing correlation with five biomarkers which are EZH2, MDM2, PCNA, STAT5A and TYMS. Importantly, the MDM2 gene showed the highest gene expression difference between HPV+ and HPV- HNSCC (Average log2FC = 1.89). Further in-silico validation in a large HNSCC cohort from TCGA and GTEx databases confirmed the over-expression of MDM2 in HPV+ compared to HPV- HNSCC patients (p = 2.39E-05). IHC scoring showed that MDM2 protein expression was significantly higher in HPV+ compared to HPV- HNSCC patients (p = 0.031). Our findings showed evidence that over-expression of MDM2, proto-oncogene, may affect the occurrence and proliferation of HPV-associated HNSCC by disturbing the p53-target genes and consequently the p53-related pathways.

Individualized Treatment Responsiveness as Quantified by Dynamic Changes in Cell Free HPV DNA in Patients Receiving Induction Chemotherapy and Definitive Chemoradiation for HPV-Related Head and Neck Cancer

<h3>Purpose/Objective(s)</h3> Studies have shown that induction chemotherapy (IC) is a viable pathway to chemoradiation therapy (CRT) de-intensification in HPV-related head and neck cancer (HNC). However, reliance on imaging alone for eligibility may incorrectly exclude cases where radiographic response lags or otherwise confounds biological response. We report serial cell free HPV DNA (cfHPV DNA) dynamics as a quantitative measure of early treatment responsiveness for HPV-related HNC patients receiving IC followed by CRT. <h3>Materials/Methods</h3> Starting Sept 26, 2021, we enrolled patients with locally advanced, high-risk HPV positive HNC who received 1-2 cycles of platinum/taxane IC followed by standard definitive CRT. Peripheral blood was collected biweekly during IC and weekly during CRT to measure cfHPV DNA levels using HPV-SEQ, a CLIA-certified assay that uses SafeSEQ technology to sensitively detect and quantify HPV16 and HPV18 DNA in plasma (Sysmex Inostics). The treating radiation oncologist delineated tumor volumes on pre- and post-IC CT simulation scans. <h3>Results</h3> At present, 86 plasma samples have been examined across 12 enrolled patients. The median age was 65 years (range: 35-79). The primary disease sites included 8 oropharynx (OPX), 2 nasopharynx, 1 sinonasal, and 1 larynx, with all tumors being high-risk HPV positive by in-situ hybridization. All patients had at least cT3 disease or cN3 disease by AJCC 8 criteria, with 7 patients having cT4 disease. Half of the patients have a >10 pack-year smoking history. Tumor volume measurements and cfHPV DNA levels at key time-points for the 8 patients who have completed IC are summarized in Table 1 below. <h3>Conclusion</h3> Serial cfHPV DNA may provide an earlier and more quantitative readout of individualized treatment responsiveness compared with imaging assessment alone in HPV-related HNC. We identify a group of patients with locally advanced disease who had complete or near-complete cfHPV DNA clearance during IC. Rapid and effective clearance of cfHPV DNA may ultimately serve as a preferred metric for identifying "exceptional responders" who are ideal biological candidates for short-course CRT after IC. Our granular cfHPV DNA dataset with biweekly measurements during IC and weekly measurements during CRT should lead to a more precise evaluation of cfHPV DNA clearance velocity and tumor response kinetics with this paradigm.

Dynamic cell free HPV DNA is an early measure of treatment responsiveness in patients receiving induction chemotherapy for HPV-related head and neck cancer.

6062 Background: Induction chemotherapy (IC) is being studied as a chemoradiation (CRT) de-intensification strategy in HPV-related head and neck cancer (HNC), but using imaging response for eligibility selection is distinctly limited by delayed correlation with biological response and difficulty in distinguishing active tumor from treatment effect. We report serial cell free HPV DNA (cfHPV DNA) dynamics as a quantitative measure of early treatment responsiveness for HPV-related HNC patients receiving IC followed by CRT. Methods: Patients with high-risk HPV-positive (by in situ hybridization), locally advanced HNC who received IC followed by definitive CRT were enrolled starting on Sept 26, 2021. Patients received 1-2 cycles of platinum/taxane IC prior to initiating standard-dose CRT. Peripheral blood cfHPV DNA levels were measured biweekly during IC and weekly during CRT with the SafeSEQ HPV test from Sysmex Inostics, an NGS-based, CLIA-certified assay designed to sensitively detect and quantify HPV16 and HPV18 DNA in plasma. Tumor volumes were assessed on the pre- and post-IC planning CT scans by the treating radiation oncologist. Results: To date, 72 plasma samples have been processed across 11 enrolled patients with median age 66 years (range: 35-79). The primary disease sites included 7 oropharynx (OPX), 1 sinonasal, 2 nasopharyngeal, and 1 larynx. All patients had at least cT3 disease or cN3 disease (AJCC 8), with 6 patients having cT4 disease. Five (45.5%) have a smoking history, each &gt; 10 pack-years. We report cfHPV DNA and tumor volume measurements at key timepoints for the 8 patients who have completed IC below. Conclusions: Serial cfHPV DNA identifies a group of locally advanced HPV-related HNC patients who have complete/near-complete cfDNA clearance during IC. This may provide an earlier readout of individualized treatment responsiveness compared to radiologic assessment, and may therefore be a preferred metric for CRT de-intensification eligibility. Clearance velocity will be evaluated with our granular biweekly IC and weekly CRT cfHPV DNA dataset to help further elucidate tumor response kinetics with this paradigm. [Table: see text]

Effects of Head and Neck Cancer Diagnosis and Treatment on Patient-Partner Intimacy

<h3>Purpose/Objective(s)</h3> Head and Neck cancer (HNC) diagnosis and treatment have the potential to significantly affect patient relationships. We aimed to understand the effects of a HNC diagnosis on patient and partner perceived intimacy at diagnosis and after treatment. Additionally, we sought to understand if the diagnosis of HPV related HNC influenced patients' and partners' levels of perceived intimacy. <h3>Materials/Methods</h3> A prospective, survey-based study was conducted using two cohorts of HNC patients and partners: HPV-positive and HPV-negative. Respondents completed a survey of questions adapted from the HPV Impact Profile, the Dyadic Adjustment Scale, and the Miller Social Intimacy Scale at two time points. Within 2 months of diagnosis prior to treatment and again after 3-6 months post treatment. Responses were then scored as: loss of intimacy (0-48), stable relationship (49-71), improvement in intimacy (72-120). Respondents were also asked whether changes in perceived intimacy were due to HPV or effects of cancer treatment. Survey responses were considered discordant if patient and partner scores equated to different levels of perceived intimacy. <h3>Results</h3> 25 patient-partner pairs completed the first survey. 68% of couples demonstrated concordant responses with 16 couples reporting increased intimacy, one couple reporting stable intimacy and none reporting decreased intimacy. 32% of patient-partner pairs showed some discordance in responses with 7 couples in which one partner reported stability and the other reported increase in intimacy and one couple in which one partner reported an increase and the other reported a decrease in intimacy. 15 patient-partner pairs completed the second survey 3-6 months post HNC treatment. 73% of patient-partner pairs demonstrated concordant responses with 8 couples reporting increased intimacy, two couples reporting stable intimacy and one couple reporting decreased intimacy. 27% of patient-partner pairs showed some discordance in responses, with four couples in which one partner reported an increase and the other reported stable intimacy. Overall scores were not significantly different between patients and partners at either timepoint (p=0.31, p=0.63). Mean scores were similar between HPV+ and HPV- groups at both timepoints (p=0.35, p=0.22); however, the patient and partner who reported loss of intimacy cited presence of HPV in diagnosis as a reason for the decline. <h3>Conclusion</h3> The majority of patients and partners surveyed reported either stable or increased intimacy both at diagnosis and after treatment. Further, most patients and partners agreed about their perceived level of intimacy. The simultaneous diagnosis of HPV related malignancy did not significantly affect intimacy scores; however, individuals who experienced a loss of intimacy reported that HPV was at the core of the decline.

MRNA and miRNA Profiles of Exosomes from Cultured Tumor Cells Reveal Biomarkers Specific for HPV16-Positive and HPV16-Negative Head and Neck Cancer.

Human papillomavirus (HPV)(+) and HPV(−) head and neck cancer (HNC) cells’ interactions with the host immune system are poorly understood. Recently, we identified molecular and functional differences in exosomes produced by HPV(+) vs. HPV(−) cells, suggesting that genetic cargos of exosomes might identify novel biomarkers in HPV-related HNCs. Exosomes were isolated by size exclusion chromatography from supernatants of three HPV(+) and two HPV(−) HNC cell lines. Paired cell lysates and exosomes were analyzed for messenger RNA (mRNA) by qRT-PCR and microRNA (miR) contents by nanostring analysis. The mRNA profiles of HPV(+) vs. HPV(−) cells were distinct, with EGFR, TP53 and HSPA1A/B overexpressed in HPV(+) cells and IL6, FAS and DPP4 in HPV(−) cells. The mRNA profiles of HPV(+) or HPV(−) exosomes resembled the cargo of their parent cells. miR expression profiles in cell lysates identified 8 miRs expressed in HPV(−) cells vs. 14 miRs in HPV(+) cells. miR-205-5p was exclusively expressed in HPV(+) exosomes, and miR-1972 was only detected in HPV(−) exosomes. We showed that HPV(+) and HPV(−) exosomes recapitulated the mRNA expression profiles of their parent cells. Expression of miRs was dependent on the HPV status, and miR-205-5p in HPV(+) and miR-1972 in HPV(−) exosomes emerge as potential discriminating HPV-associated biomarkers.

Prevalence of comorbidities and effect on survival in survivors of human papillomavirus-related and human papillomavirus-unrelated head and neck cancer in the United States.

The increasing incidence of human papillomavirus (HPV)-related head and neck cancer (HNC) has led to the increasing prevalence of survivors, yet to the best of the authors' knowledge the prevalence of comorbidities during the survivorship period and their effects on survival are relatively unknown. In this retrospective cross-sectional study, individuals with a first incident primary diagnosis of HNC from 2004 through 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked databases were included in the analysis and classified as patients with HPV-related or HPV-unrelated HNC. The presence of 30 comorbid conditions of interest was identified. Associations between comorbidity and treatment group as well as overall survival were evaluated. The study population consisted of 8025 patients with HPV-unrelated HNC and 2499 patients with HPV-related HNC. Hypertension, congestive heart failure, cerebrovascular disease, and chronic obstructive pulmonary disease all were found to be highly prevalent at the time of the cancer diagnosis and increased over time for both groups. These comorbidities were found at significantly lower rates in the HPV-related HNC population, yet were associated with an increased risk of death in both groups. The probabilities of developing cancer-related comorbidities such as pneumonia, dysphagia, weight loss, malnutrition, and dental issues rose significantly in both groups after treatment but were more likely in patients with HPV-related HNC. In both groups of patients, the presence of each comorbidity either at the time of diagnosis or during survivorship was associated with a significantly increased risk of death. There is a large burden of comorbidities in both patients with HPV-related and HPV-unrelated HNC, both of which are associated with decreased survival. Oncologic surveillance should not be limited to the evaluation of disease status, but also should include screening for the highly prevalent conditions associated with the risk of death.

Differential regulation of NF-kB and IRF target genes as they relate to fatigue in patients with head and neck cancer

Previous studies have linked plasma inflammatory markers to elevated fatigue in patients with head and neck cancer (HNC). To identify the molecular mechanisms underlying this association, we conducted promoter-based bioinformatics analyses to determine the relationship between fatigue and specific gene expression profiles associated with inflammation in human papillomavirus (HPV)-related and -unrelated HNC patients undergoing treatment. Patients with newly diagnosed HNC without distant metastasis were assessed at baseline (pre-radiotherapy) and one-month post-radiotherapy. Fatigue was measured by the Multidimensional Fatigue Inventory. Genome-wide gene expression profiles were collected from peripheral blood mononuclear cells (PBMC). Promoter-based bioinformatics analyses were employed to identify transcription control pathways underlying transcriptomic correlates of fatigue in the sample as a whole and in HPV-related and HPV-unrelated HNC patients separately. In transcriptome profiling analyses of PBMC from 44 patients, TELiS bioinformatics analyses linked fatigue to increased nuclear factor-kappa B (NF-kB) transcriptional activity and decreased interferon regulatory factor family (IRF) transcription factor activity. Patients with HPV-related HNC showed lower levels of fatigue-related gene expression profile compared to HPV-unrelated HNC. Fatigue in HNC patients undergoing treatment is associated with gene expression profiles consistent with the conserved transcriptional response to adversity (CTRA) characterized by increased proinflammatory and decreased anti-antiviral transcriptional activity. Interestingly, this CTRA response was mitigated in patients with HPV-related HNC and may explain the lower level of fatigue they experience relative to HPV-unrelated HNC.

Human Papilloma Virus and Autophagy.

Human papilloma viruses (HPVs) are a group of double-stranded DNA viruses known to be the primary cause of cervical cancer. In addition, evidence has now established their role in non-melanoma skin cancers, head and neck cancer (HNC), and the development of other anogenital malignancies. The prevalence of HPV-related HNC, in particular oropharyngeal cancers, is rapidly increasing, foreseeing that HPV-positive oropharyngeal cancers will outnumber uterine cervical cancers in the next 15–20 years. Therefore, despite the successful advent of vaccines originally licensed for cervical cancer prevention, HPV burden is still very high, and a better understanding of HPV biology is urgently needed. Autophagy is the physiological cellular route that accounts for removal, degradation, and recycling of damaged organelles, proteins, and lipids in lysosomal vacuoles. In addition to this scavenger function, autophagy plays a fundamental role during viral infections and cancers and is, therefore, frequently exploited by viruses to their own benefit. Recently, a link between HPV and autophagy has clearly emerged, leading to the conceivable development of novel anti-viral strategies aimed at restraining HPV infectivity. Here, recent findings on how oncogenic HPV16 usurp autophagy are described, highlighting similarities and differences with mechanisms adopted by other oncoviruses.

Unsupervised exercise in survivors of human papillomavirus related head and neck cancer: how many can go it alone?

Patients with human papillomavirus (HPV)-related head and neck cancer (HNC) have a better prognosis relative to other types of HNC, making survivorship an emerging and critical issue. Exercise is a core component of survivorship care, but little is known about how many survivors of HPV-related HNC can safely be advised to start exercising on their own, as opposed to needing further evaluation or supervised exercise. We utilized guidelines to identify health issues that would indicate value of further evaluation prior to being safely prescribed unsupervised exercise. We performed a retrospective chart review of 150 patients with HPV-related HNC to assess health issues 6months after completing definitive therapy. Patients with at least one health issue were deemed appropriate to receive further evaluation prior to prescription for unsupervised exercise. We utilized logistic regression to identify clinical and demographic factors associated with the need for further evaluation, likely performed by outpatient rehabilitation clinicians. In this cohort of patients, 39.3% could safely be prescribed unsupervised exercise 6months after completing definitive therapy. On multivariable regression, older age, BMI >30, and receipt of radiation were associated with an increased likelihood for requiring further evaluation or supervised exercise. Over half of patients with HPV-related HNC would benefit from referral to physical therapy or an exercise professional for further evaluation to determine the most appropriate level of exercise supervision, based upon current guidelines. Development of such referral systems will be essential to enhance survivorship outcomes for patients who have completed treatment.

Practices regarding human Papillomavirus counseling and vaccination in head and neck cancer: a Canadian physician questionnaire

BackgroundHuman papillomavirus (HPV) has recently been implicated as a causative agent in a rapidly growing number of oropharyngeal cancers. Emerging literature supports the hypothesis that HPV vaccination may protect against HPV-related head and neck cancer (HNC) in addition to HPV-related cervical and anogenital disease. While the association between HPV infection and cervical cancer is widely understood, its relation to HNC is less well known. The purpose of this study was to better understand HPV counseling practices for infection and vaccination in relation to HNC of primary care physicians (PCPs), Obstetricians/Gynecologists (OBGYNs), and Otolaryngology - Head and Neck Surgeons (OHNSs) in Canada.MethodsA Canada-wide electronic questionnaire regarding counseling practices on HPV infection, transmission, and vaccination was designed and distributed to PCPs, OBGYNs, and OHNSs across Canada through electronic and paper-based methods. Basic Descriptive statistics were used to analyze responses.ResultsIn total, 337 physicians responded (239 family physicians, 51 OHNSs, 30 OBGYNs, and 17 pediatricians). Three out of four PCPs reported routine counseling of their patients regarding HPV infection, transmission, and vaccination. Among this group, 68% reported “never” or “rarely” counseling patients that HPV can cause HNC. The most commonly reported reason that PCPs cited for not counseling was a lack of knowledge. The majority of OHNSs (81%) and OBGYNs (97%) counseled patients regarding HPV infection, transmission, and vaccination. However, very few OHNSs (10%) regularly counseled patients with HPV-related HNC about HPV-related anogenital cancer. Similarly, very few OBGYNs (18%) regularly counseled patients with HPV related cervical/anogenital cancer about HPV related HNC.ConclusionsThe rate of counseling on HPV infection, transmission, and vaccination in relation to HNC among PCPs is low. The most common reason is a lack of knowledge. Specialists rarely counsel patients with confirmed HPV-related cancer about other HPV-related malignancies. More research is needed on the relationship between different HPV-related cancers in order to better inform counseling practices.

Human Papillomavirus and Head and Neck Cancer: Psychosocial Impact in Patients and Knowledge of the Link – A Systematic Review

Head and neck cancer (HNC) currently affects approximately 11 200 people in the UK, with an increasing proportion known to be caused by the human papillomavirus (HPV). We undertook a systematic review of studies measuring the psychosocial impact of HPV-related HNC and also studies measuring knowledge about the link between HPV and HNC among different populations. Searches were conducted on MEDLINE, Embase, PsycINFO, CINAHL Plus and Web of Science, with reference and forward citation searches also carried out on included studies. Studies were selected if they (i) were original peer-reviewed research (qualitative or quantitative), (ii) mentioned HPV and HNC, (iii) measured an aspect of the psychosocial impact of the diagnosis of HPV-related HNC as the dependent variable and/or (iv) measured knowledge of the association between HPV and HNC. In total, 51 papers met the inclusion criteria; 10 measuring psychosocial aspects and 41 measuring knowledge of the link between HPV and HNC. Quality of life in those with HPV-positive HNC was found to be higher, lower or equivalent to those with HPV-negative HNC. Longitudinal studies found quality of life in patients was at its lowest 2–3 months after diagnosis and some studies found quality of life almost returned to baseline levels after 12 months. Knowledge of the link between HPV and HNC was measured among different populations, with the lowest knowledge in the general population and highest in medical and dental professionals. Due to the limited studies carried out with patients measuring the psychosocial impact of a diagnosis of HPV-positive HNC, future work is needed with the partners of HPV-positive HNC patients and health professionals caring for these patients. The limited knowledge of the association between HPV and HNC among the general population also indicates the need for research to explore the information that these populations are receiving.

Incidence trends of human papillomavirus-related head and neck cancer in Taiwan, 1995-2009.

Recent studies suggested that human papillomavirus (HPV) is an emerging risk factor of head and neck cancer (HNC), particularly for oropharyngeal cancer. Studies from the West showed a rising trend of HPV-related HNC despite a decrease of the overall HNC incidence. In contrast, the overall HNC incidence in Taiwan has continued to rise. It is not clear whether the incidence trends of HPV-related HNC in Taiwan have a similar pattern to those from countries with an overall decreasing incidence of HNC. This study examined the incidence trends of HPV-related and HPV-unrelated HNC in Taiwan using data from the Taiwan Cancer Registry. Our results showed that the incidence trends of HPV-related and HPV-unrelated HNC in Taiwan both rose during 1995-2009. The incidence of HPV-related HNC (1.3 per 100,000 in 1995 to 3.3 in 2009, annual percentage change (APC) = 6.9, p < 0.0001) rose more rapidly than the incidence of HPV-unrelated HNC (10.4 per 100,000 in 1995 to 21.7 in 2009, APC = 5.0, p < 0.0001). The rising trend of HPV-related HNC was particularly prominent for HNC occurring in tonsil (APC = 8.2, p < 0.0001), in men (APC = 7.5, p < 0.0001), and in those aged between 40 and 50 years (APC = 8.5, p < 0.0001). Although the overall incidence of HNC in Taiwan has continued to increase, the most rapid rise is in the HPV-related HNC. This suggests that similar to the Western world, HPV-related HNC is becoming an important public health issue in Taiwan.

IS8-7 - Optimization of Combined Modality Therapy for Locoregionally Advanced Head and Neck Cancer

ABSTRACT In recent years, several treatment principles have been firmly established for the treatment of a majority of patients with locoregionally advanced head and neck cancer (HNC). These include (i) therapies are administered with curative intent and (ii) organ preservation is pursued whenever possible. In order to achieve these goals, several tools have emerged as evidence-based approaches. Among these are concomitant chemoradiotherapy, usually with cisplatin as radiation sensitizer, as well as induction chemotherapy with the combination of cisplatin, docetaxel and fluorouracil being best supported by randomized clinical trials. It is unclear which of these approaches might be superior, although concurrent chemoradiotherapy continues to have the most abundant database to support its use. Current questions are whether or not induction chemotherapy and concomitant chemoradiotherapy should be combined in sequence. A recent randomized trial comparing concomitant chemoradiotherapy versus induction chemotherapy followed by concurrent chemoradiotherapy has been completed and results will be available this spring. There are also questions how to best treat patients with HPV-related HNC. It is possible that less intensive treatment might lead to similar cure rates as the current standard treatment approach. Furthermore, the integration of novel molecular diagnostics and therapeutic agents is under investigation.

Controversies in the Locoregional Management of Head and Neck Cancer

Head and neck cancer (HNC) is a heterogeneous combination of various sites and types of disease. This manuscript elaborates on 3 important and current issues: the emerging role of human papilloma virus (HPV) in oropharyngeal cancer (OPC), current considerations in systemic therapy for advanced disease, and evolving treatment of the neck. Exogenous carcinogens, most notably tobacco, have classically been implicated in the development of HNC. A large increase in the incidence of OPC has occurred in the past few decades, predominantly in nontobacco users, and is caused by HPV. This disease is unique in many respects and presents an opportunity for novel therapeutic approaches. Because the prognosis for HPV-related HNC is better, regardless of whether surgery or radiation is used as the primary therapy, the reduction of treatment-related morbidity has assumed increasing importance and provides unique opportunities and challenges for de-escalation of therapies. Radiotherapy (RT) and concurrent cisplatin is the most commonly used nonsurgical platform for locally advanced disease. New data suggest that viable alternatives exist to the typical 3 cycles of bolus high-dose cisplatin. The role of RT and concurrent taxanes remains less understood. Similarly, the value of integrating epidermal growth factor inhibition and concurrent chemoradiation is under continuing investigation. The use of PET scanning is changing the traditional use of adjuvant neck dissection after RT or chemoradiation. Recent data support the use of surgery in the presence of a positive posttreatment PET, and observation in the setting of a negative posttreatment scan.

Human papillomavirus seropositivity and risks of head and neck cancer

We examined antibody response to VLP HPV-16, HPV-16 E6 and E7 antibodies as potential seromarkers of HPV-related head and neck cancer (HNC). The study included 204 HNC cases and 326 controls evaluated for HPV presence in sera using ELISAs for anti-HPV VLP antibodies and HPV-16 E6 and/or E7 antibodies, and in tumor tissue using PCR and DNA sequencing. Anti-HPV-16 VLP was detected in 33.8% of cases and 22.4% of controls, anti-E6 in 20.6% of cases and 0.9% of controls and anti-E7 in 18.6% of cases and 0.6% of controls. HPV-16 DNA was detected in 26.1% of tumors. The adjusted risk of HNC was elevated among those seropositive for HPV-16 VLP (odds ratio (OR) = 1.7, 1.1-2.5), E6 (OR = 32.8, 9.7-110.8) or E7 (OR = 37.5, 8.7-161.2). Compared to HPV DNA-negative/seronegative cases, tumor HPV-16 cases had increased risk of detection with anti-VLP antibodies (OR = 6.8, 3.1-14.9). The odds were more pronounced among cases seropositive for E6 (OR = 69.0, 19.3-247) or E7 (OR = 50.1, 14.7-171). Antibodies against E6 or E7 were associated with risk of cancer in the oral cavity (OR = 5.1, 1.2-22.4) and oropharynx (OR = 72.8, 16.0-330), and with disease characteristics: stage, grade and nodal status. Anti-E6 and/or E7 antibodies were found in 74% of tumor HPV-16 positive cases but in only 5% of tumor HPV-negative cases (K =0.7, 0.6-0.8) suggesting good correlation between the serologic marker and HPV tumor status. Antibodies to HPV-16 E6 and/or E7 represent a more specific biomarker than anti-HPV-16 VLP of an HPV-related HNC. Because of the survival advantage of HPV-related HNC, HPV-16 E6/E7 detection may be useful in therapy targeted for HPV-related tumors.