Oropharyngeal HPV Research Articles

Improving HPV-Related Oropharyngeal Cancer Knowledge and HPV Vaccination Rates via Virtual Workshops.

To validate the efficacy of a virtual, interdisciplinary workshop in improving HPV knowledge, and vaccination practices among primary care and dental trainees. A virtual platform was utilized to hold HPV educational workshops with primary care and dental trainees. Online surveys were distributed before and after the 1-h interactive workshop, led by otolaryngology residents. Surveys included the workshop's impact on (a) improving knowledge of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and (b) affecting change in HPV vaccination practices. The vaccination rates of trainees were recorded prior to and after workshop attendance. After the workshop, participants demonstrated significantly improved scores related to knowledge of HPV in the head and neck (p = 0.003) and showed an increased comfort level with counseling on HPV vaccination (p = 0.002). Respondents were also more aware that the HPV vaccine is approved to prevent OPSCC (61% vs. 95%, p < 0.05). Ninety-seven percent of respondents stated that the workshop changed their HPV vaccination practices, and 95% of those not fully vaccinated stated they would now be more likely to receive the vaccine themselves. There was a significant increase in the average number of HPV vaccines administered at the studied trainee clinic, from 16.83 vaccines/month to 37.6 vaccines/month (percent increase = 123%) in 5 months following the workshop (p = 0.002). The present interactive virtual workshop demonstrates efficacy in improving HPV-related knowledge and vaccination practices among trainees. The virtual nature of the course facilitates knowledge transfer and can be used to foster multi-institutional partnerships regarding medical education and vaccination efforts. 4 Laryngoscope, 134:3096-3101, 2024.

Association of oropharyngeal cancer HPV status with diffusion-weighted MR imaging and FDG-PET parameters

BackgroundHuman papilloma virus (HPV) infection is an important risk factor in oropharyngeal cancer. Several studies have analyzed the association of tumoral HPV status and different imaging parameters in FDG-PET/CT and magnetic resonance (MR) diffusion-weighted imaging (DWI), with contradictory findings. In this retrospective study, the influence of HPV-status on different parameters in FDG-imaging and MR DWI is investigated. MethodsIn this retrospective, single-center study we analyzed patients diagnosed with oropharyngeal cancer between January 2018 and December 2020 at a tertiary center in Switzerland. HPV status was assessed via p16 immunohistochemistry and/or PCR. Standardized uptake value (SUV), total lesion glycolysis (TLG) and apparent diffusion coefficient (ADC) were measured in pretreatment imaging (FDG-PET/CT, FDG-PET/MR, DWI MR). Statistical analysis was performed using Mann-Whitney-U tests. All p values reported are two-sided, and p values < 0.05 were considered statistically significant. Results142 patients were included. 67% of tumors were HPV-positive. Mean SUVmax in FDG-PET was 15.0+/-5.9 for HPV-positive tumors and 18.6+/-9.7 for HPV-negative tumors (p = 0.15). Mean ADC was 1109 x 106 mm2/s+/-326.8 for HPV-positive tumors and 1045.8 x 106 mm2/s+/-467.0 for HPV-negative tumors (p = 0.76). Conclusionand Relevance: We found no correlation between oropharyngeal carcinoma HPV status and any of the analyzed imaging parameters.

Is an oropharyngeal HPV infection more frequently detectable in women with a genital HPV infection?

If not eliminated by the immune system and persisting over years, oropharyngeal high-risk HPV infection can lead to cancer development in the oropharynx. HPV infection is very commonly found in the genital region and can serve as an HPV reservoir. In this study, we investigate whether women with a genital HPV infection are at a higher risk of harboring an undetected oropharyngeal HPV infection via genital-oropharyngeal transmission. Women presenting for routine gynecological checkups were included in this study. All participants received an HPV brush test from the genital region as well as from the oropharynx. Additionally, probable risk factors for an HPV infection were assessed in a structured questionnaire. 142 women were included in this study. The rate of oropharyngeal HPV infection was low with 2/142 (1,4%) women positive for a low-risk HPV genotype. In the genital brush test, 54/142 (38%) women were tested HPV positive of which 41/142 (29%) were positive for a high-risk HPV genotype. The rate of an oropharyngeal HPV detection in our population was low with 2/142 women harboring a low-risk HPV infection.

Anal and oropharyngeal HPV distribution in HIV-negative multipartner MSM using self-sampling kits for HIV and sexually transmitted infection screening.

Men who have sex with men (MSM) are at high risk of sexually transmitted infections, among which HPV infections are particularly prominent. We took advantage of the MémoDépistages study to evaluate HPV distribution at anal and oropharyngeal sites in HIV-negative multipartner MSM. HPV DNA was detected in 82% (n = 344) of anal and 11% (n = 45) of oropharyngeal self-collected samples taken from 421 participants. Multiple HPV types were detected in 70% of anal samples, and single HPV types in 91% of oropharyngeal samples. HPV16 was the most frequent type detected in the anus, followed by HPV6, HPV51, and HPV52. HPV6, HPV16, and HPV11 were the most prevalent types in the oropharynx. HPV targeted by the nonavalent vaccine was detected in 71% and 50% of HPV-positive anal and oropharyngeal samples, respectively. The main risk factor associated with HPV detection was frequenting gay meeting places, living in large cities, and having an anal Chlamydia trachomatis/Neisseria gonorrhoeae infection. In this cohort of highly sexually active MSM, HPV detection was highly frequent and rendered them at high risk of precancerous and cancerous lesions. Universal vaccination against HPV before sexual debut is an important public health strategy to prevent HPV-associated cancers in this highly vulnerable population of HIV-negative MSM.

HPV Infection of the Oropharyngeal, Genital and Anal Mucosa and Associated Dysplasia in People Living with HIV.

The main objectives were to describe the prevalence of HPV, its genotypes and HPV-associated dysplastic lesions in the oropharyngeal mucosa of PLHIV and related factors. This cross-sectional prospective study consecutively enrolled PLHIV attending our specialist outpatient units. At visit, HIV-related clinical and analytical variables were gathered, and oropharyngeal mucosa exudates were taken to detect HPV and other STIs by polymerase chain reaction. Samples were also taken from the anal canal of all participants and from the genital mucosa of the women for HPV detection/genotyping and cytological study. The 300 participants had a mean age of 45.1 years; 78.7% were MSM and 21.3% women; 25.3% had a history of AIDS; 99.7% were taking ART; and 27.3% had received an HPV vaccine. HPV infection prevalence in the oropharynx was 13%, with genotype 16 being the most frequent (2.3%), and none had dysplasia. Simultaneous infection with Treponema pallidum (HR: 4.02 (95% CI: 1.06-15.24)) and a history of anal HSIL or SCCA (HR: 21.52 (95% CI: 1.59-291.6)) were risk factors for oropharyngeal HPV infection, whereas ART duration (8.8 vs. 7.4 years) was a protective factor (HR: 0.989 (95% CI: 0.98-0.99)). The prevalence of HPV infection and dysplasia was low in the oropharyngeal mucosae. A higher exposure to ART was protective against oral HPV infection.

Human papillomavirus detection in oral rinses and history of tonsillectomy in U.S. adults

PurposeThis study aims to elucidate any relationship between prior tonsillectomy and the presence of oropharyngeal HPV DNA found in screening mouth rinses. Materials and methodsA cross sectional study was conducted using the 2011–2014 National Health and Nutrition Examination Survey (NHANES). Participants between 40 and 69 were included in the study and medical, surgical, and sexual health history were recorded. Multivariable analyses were conducted to examine factors associated with HPV prevalence in oral rinse samples. ResultsA total of 4825 participants were recorded with 21.1 % having a history of tonsillectomy. In the no tonsillectomy group, 8.6 % of respondents had a positive oral rinse for HPV, while 7.2 % of those with a tonsillectomy had a positive rinse sample. There was no association between age and HPV prevalence (OR = 1.04, 95 % CI: [1.00–1.07]). When controlling for demographics, medical history, and sexual behaviors, tonsillectomy history was not shown to have an association with HPV (OR = 0.86, 95 % CI: [0.53–1.40]). However, men, Hispanics, smokers, and those with higher lifetime sexual partners had increased odds of having a positive HPV oral rinse sample which was statistically significant. ConclusionOur data showed that a history of tonsillectomy was not significantly associated with the presence of HPV in an oral rinse. However, a significant relationship was seen between the presence of HPV in oral rinses and certain demographic factors such as male gender, Hispanic race, smoking history, and increased sexual partners.

Role of Epstein-Barr Virus and Human Papilloma Virus in the Development of Oropharyngeal Cancer: A Literature Review.

The aim of this review was to describe the association and related mechanisms between HPV, EBV, and the development of oral and oropharyngeal cancer. A search for scientific evidence was carried out in electronic databases (MEDLINE/PubMed, SciELO). It was found that, among the carcinogenic mechanisms of HPV, E6 and E7 proteins are responsible for the malignization process, inhibiting tumor suppressors p53 and pRb. As to EBV, it was noted that its “hit and run” phenomenon manipulates the host epigenetic mechanism, triggering the tumor process without the virus being currently present; a “cellular reprogramming” is essentially generated, causing heritable changes in gene expression without DNA mutation. In conclusion, there is an association between oropharyngeal carcinogenesis and HPV and also between the former and EBV. Further studies are required to clarify the causal mechanisms and impact of both viruses on cancer development and to obtain biomarkers of greater specificity in the case of EBV.

MDM2 is a useful diagnostic marker for nasopharyngeal carcinoma

BackgroundThe MDM2 gene appears to be involved in the development of nasopharyngeal carcinoma. The aim of this study was to examine MDM2 expression in a series of nasopharyngeal carcinoma biopsies to explore its potential diagnostic significance. MethodsThe study cohort consisted of 26 nasopharyngeal carcinomas, including 22 EBV positive non-keratinizing squamous cell carcinomas (NKSCC), 1 EBV negative NKSCC and 3 EBV negative keratinizing SCC. For comparison, we selected 48 oropharyngeal carcinomas, including 17 HPV positive SCC (14 non-keratinizing and 3 keratinizing) and 31 HPV negative SCCs (28 keratinizing and 3 non-keratinizing). In addition, we examined MDM2 expression in a group of 26 cervical lymph node metastases, including 5 with EBV positive nasopharyngeal NKSCC and 21 from oropharyngeal carcinoma (18 non keratinizing HPV positive, 1 keratinizing HPV positive, 1 keratinizing HPV negative and 1 non-keratinizing HPV negative). Finally, 2 bone metastases from EBV positive nasopharyngeal NKSCC were also included. A tissue microarray was constructed from formalin-fixed paraffin embedded tumor tissue specimens. Sections were immunostained for MDM2 and in situ hybridization for EBER and CISH analysis for the MDM2 gene were also conducted in all cases. ResultsOverall, MDM2 positivity was detected in 28 of 102 SCCs (27.2 %). MDM2 positivity was significantly more frequent in EBV positive NKSCC (80 %) than in oropharyngeal HPV positive NKSCC (6.1 %) and keratinizing SCCs (9.4 %) (p < 0.001, Pearson chi square). Considering only the primary tumors, 86.4 % of the nasopharyngeal carcinomas were positive, versus 13.5 % of the oropharyngeal carcinomas (p < 0.001, Pearson chi square). Considering the lymph node metastases, 3 of 5 EBV positive carcinomas with nasopharyngeal primary were positive, whereas only one of the HPV positive carcinomas was positive. Finally, both the bone metastases from EBV positive nasopharyngeal carcinoma were positive for MDM2. No amplification of the MDM2 gene was identified by in situ hybridization analysis. ConclusionsOur data indicate that MDM2 could be a valuable diagnostic marker to support the diagnosis of nasopharyngeal EBV positive NKSCC.

Factors associated with the decreasing rate of oropharyngeal cancer in young adults in the United States.

10534 Background: To evaluate trends of HPV-associated oropharyngeal cancers and HPV infections in the United States. Methods: Data was extracted from the United States Cancer Statistics Public Use Database (USCS) between 2001 and 2017 and the National Health and Nutrition Examination Survey (NHANES) between 2011 to 2016. Data on oropharyngeal squamous cell carcinoma (OSCC) was obtained from the USCS database. HPV vaccination and screening (oral washings) data were obtained from NHANES. Based on CDC guidelines, HPV strains were further subdivided into high-risk strains (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68). Results: Based on USCS, oropharyngeal cancer incidence rates have increased in males by 1.64% every year (p &lt; 0.001) while remaining stable in females over the last 17 years. Oropharyngeal cancers have increased for all age groups over the age of 55, with the largest increase seen in those between the ages of 65-69 years old (p &lt; 0.001). However, individuals between the ages of 30-34 had the largest decrease in oropharyngeal cancers over the same time period (p = 0.016). Based on race, Whites had the highest incidence rates at 5.12/100,000 followed by 2.99 in Blacks, 2.32 in Hispanics, and 1.11 in Asians. By geographical region, the incidence was found to be the highest in the Midwest with 4.68/100,000 and the lowest in the West at 3.78. Our intersectional analysis showed that White males in the South aged 65-69 had the highest incidence of oropharyngeal cancers at 40.57/100,000 and this same group aged 60-64 had the highest annual increase at 4.65% (p &lt; 0.001). Using the NHANES database, we showed that those with greater than 4 lifetime sexual partners have a 3-fold higher risk of high risk HPV infection compared to those with 4 or under (7.1% vs 1.9%, p &lt; 0.0001). 8.8% of current smokers are infected with high risk oral HPV compared to only 3.9% of non smokers (p &lt; 0.001). The incidence of any HPV infection for those &lt;39 years old was 5.9% in 2011 and 4.7% in 2016 (p = 0.4723). In contrast, the incidence in those &gt; 39 years old was 6.6% in 2011 and 6.4% in 2016 (p = 0.99). On multivariate analysis, males have a 4-fold higher risk of high risk HPV infections compared to females (4.45, 95% CI: 2.94 - 6.74, p &lt; 0.0001). Those with five or more sexual partners have 7-fold higher rate of high risk oral HPV infections compared to those without any sexual partners (7.15, 95% CI: 1.94 - 26.3, p = 0.0039). Furthermore, current smokers (1.81, 95% CI: 1.17 - 2.77, p = 0.0081) and three to four drinks per day (1.63, 95% CI: 1.05 - 2.55, p = 0.0312) have an increased risk of high risk oral HPV infections. Conclusions: Over the last 18 years, oropharyngeal cancers are increasing in individuals over the age of 55, particularly White males residing in the South. Individuals with greater than 4 lifetime sexual partners, current smokers, and those who consume three to four drinks per day have increased HPV infectivity rates.

The impact of radiomics for human papillomavirus status prediction in oropharyngeal cancer: systematic review and radiomics quality score assessment

PurposeHuman papillomavirus (HPV) status assessment is crucial for decision making in oropharyngeal cancer patients. In last years, several articles have been published investigating the possible role of radiomics in distinguishing HPV-positive from HPV-negative neoplasms. Aim of this review was to perform a systematic quality assessment of radiomic studies published on this topic.MethodsRadiomics studies on HPV status prediction in oropharyngeal cancer patients were selected. The Radiomic Quality Score (RQS) was assessed by three readers to evaluate their methodological quality. In addition, possible correlations between RQS% and journal type, year of publication, impact factor, and journal rank were investigated.ResultsAfter the literature search, 19 articles were selected whose RQS median was 33% (range 0–42%). Overall, 16/19 studies included a well-documented imaging protocol, 13/19 demonstrated phenotypic differences, and all were compared with the current gold standard. No study included a public protocol, phantom study, or imaging at multiple time points. More than half (13/19) included feature selection and only 2 were comprehensive of non-radiomic features. Mean RQS was significantly higher in clinical journals.ConclusionRadiomics has been proposed for oropharyngeal cancer HPV status assessment, with promising results. However, these are supported by low methodological quality investigations. Further studies with higher methodological quality, appropriate standardization, and greater attention to validation are necessary prior to clinical adoption.

Influence of Tumor Site on Survival in Young Patients with Head and Neck Squamous Cell Carcinoma.

The number of patients under the age of 45 diagnosed with head and neck squamous cell carcinomas (HNSCC) is increasing, probably due to the incidence of oropharyngeal cancers. Comparisons of HNSCC in young and old patients regarding tumor site and survival in sample sizes of relevance are rarely published. The aim of the study was to analyze the differences in survival between age groups dependent on tumor site and the influence of oropharyngeal cancers on the rising rates of HNSCC in the young. The records of 4466 patients diagnosed with HNSCC were reviewed retrospectively. Patients younger than 45 years were divided further into four subgroups for specific age differences in the young. The influences of patient and clinicopathological characteristics on survival were assessed using Kaplan–Meier analyses. Among the patient cohort, 4.8% were younger than 45 years. Overall survival (OS) in these patients was better, with a 5-year OS of 66.1% (vs. 46.4%), while relapse-free survival (RFS) was better in the older patient population, with a 5-year RFS of 74.9% (vs. 68.1%). Decreased RFS in the young was found for advanced tumor stages and tumor sited at the larynx. Hypopharynx and advanced stages were independent risk factors for OS under 45 years. Overall, 44.4% of all HNSCC in patients under 30 years were nasopharyngeal cancers, and incidence decreased with age. The incidence of oropharyngeal cancers increased significantly with age. Better OS in the young may be explained by lower tumor and disease stages, whereas oropharyngeal tumors and HPV were not found to cause rising rates of HNSCC. Laryngeal malignancies in young patients might be related to an increased malignant potential and should, consequently, be treated as such.

Oral and Oropharyngeal HPV prevalence in South Africa A systematic review and meta-analysis

Prevalence data for HPV infection in the head and neck in Southern African populations is lacking. In addition to cervical cancer, this sexually transmitted oncogenic virus is responsible for a subset of head and neck cancer and is transmitted via oral sexual routes, and through other forms of intimate contact between anatomical sites lined by mucosa. This systematic review and meta-analyses aimed to synthesize data for the prevalence of head and neck HPV infection in South Africa. Original research papers from South Africa reporting on the prevalence of HPV in the head and neck was systematically reviewed using PubMed, Ovid Medline, Embase and the Cochrane Library. A meta-analysis on the prevalence data wasconducted for 16 papers that met the inclusion criteria.

Sexual Behavior and High-Risk HPV Infection in the Head and Neck

In the second half of the 20th century, the sexual revolution went hand in hand with changes in common sexual practices. At the turn of the millennium, an increase in the detection rate of HPV-positive oropharyngeal carcinomas (OPC) in the USA was observed for the first time. An increase in the OPC was also observed in Europe. It was shown that this increase was due to HPV-positive OPC. However, the detection rate of the HPV-positive OPC has national and regional differences. Within Europe, the highest detection rate is in Northern Europe (56,5 %), followed by Central Europe (37,6 %). An association between patients with OPC and ≥ 6 sexual partners (OR = 1,25) and ≥ 4 oral sex partners (OR = 2,25) has been described. An HPV infection is usually asymptomatic and eliminated by the immune system within a few months. The persistence of the virus is oncogene. Smoking favors virus persistence, which is why the combination of smoking and oral sex with ≥ 5partners is a particular risk factor. It was also examined whether partners from patients with cervical cancer have an increased oropharyngeal HPV infection rate. There was no definite declaration on this, but further investigations are required. Oral condoms or dental dams are suitable for the prevention of an oral HPV infection. The studies regarding the effectiveness of HPV vaccination for the prevention of an OPC are poor. Authors described a significantly lower detection rate of oral HPV infection in vaccinated people than in non-vaccinated people (0,11 % vs. 1,61 %; p = 0,008).

Comparison of PapilloCheck and Linear Array to Detect and Differentiate Human Papillomaviruses in Cervical and Tonsillar Smears from Females with Cervical Intraepithelial Lesions.

A subgroup of oropharyngeal squamous cell carcinomas (OSCCs) are causally linked to infection with high-risk human papillomaviruses (HR-HPVs). To evaluate the prevalence of simultaneous oral HPV infection in females with cervical high-grade squamous intraepithelial lesions (HSIL), tonsillar- and cervical smears were collected simultaneously from 73 patients and analyzed for HPV using two commercial assays, PapilloCheck (Greiner-Bio-One) and Linear Array (Roche). Only 3/73 (4.1%) tonsillar smears were HPV positive (HPV+), with HPV types 16, 35, and 45, respectively, detected by both assays (100% agreement). Concordant results were also found in 60/66 (91%) evaluable cervical smears. Of specimens, positive by both assays, typing results completely coincide in 71% (all types are identical) and partially coincide in 27% (at least one type is identical). Taken together, results of HPV detection and typing by PapilloCheck and Linear Array are highly congruent and confirm the low prevalence of HR-HPV in tonsillar smears of patients with HSIL of the uterine cervix. Our data indicate low prevalence of oropharyngeal HPV infection in patients with high-grade cervical dysplasia. The low detection rate was confirmed by using two different commercial assays with largely consistent results of HPV detection and typing, but with some variation for particular HPV types. Comparative testing of larger numbers is required to identify the HPV types prone to escape detection with particular assays.

The feasibility of the cervical HPV screening method as a model for a public oropharyngeal HPV screening

The feasibility of the cervical HPV screening method as a model for a public oropharyngeal HPV screening

A Matched Pair Analysis of Patients With HPV-Associated Carcinoma of Unknown Primary With T1-2 HPV-Associated Oropharynx Cancer: Implications for Clinical Trial Design

Patients (pts) with human papillomavirus associated (HPV+) cancer of unknown primary (CUP) are generally excluded from clinical trials, despite surgical series that report detection rates of occult oropharynx primaries of >80%. We performed a matched pair analysis to compare outcomes between T0N+M0 HPV+ CUP and T1-2N+M0 HPV+ oropharynx cancer of known primary (OPX). Pts with cT1-2N1-3M0 HPV+ OPX or T0N1-3M0 HPV+ CUP treated with curative intent between 1999 and 2016 were identified in an IRB approved database. CUP was defined as biopsy proven HPV+ cervical lymph node metastasis without an identified primary tumor despite imaging and direct visualization/biopsy. HPV status was confirmed by p16 IHC staining and/or by ISH for HPV DNA. For a subgroup of CUP pts with an unknown HPV status, we performed multiple imputation analysis using a training and validation cohort of 447 pts with known oropharyngeal primary and HPV status and then applied the model to CUP pts. We then included CUP pts with a >80% probability of being HPV+. Matched pair analysis was performed using a nearest neighbor propensity technique (MatchIt package in R). Pts were matched based on age, gender, N-stage, performance status, smoking status, pack-years, chemotherapy use and neck dissection. Pts were also matched according to either a favorable (N1-2b and <10 pk-yrs) or unfavorable (N2c-3 or >10 pk-yrs) risk stratification designations per current NRG oncology clinical trial enrollment criteria. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier analysis. Of 313 pts with T1-2N1-3 OPX, 48 were matched to 48 HPV+ CUP pts (32 confirmed and 16 imputed HPV-status). All pts received curative radiotherapy (RT) and all CUP pts had potential oropharynx mucosal sites targeted. Overall, 40% of CUP and 27% of OPX first underwent primary surgery and/or neck dissection followed by adjuvant RT, while the remaining pts were treated non-operatively. Chemotherapy was used in 63% and 71% of each group, respectively. Median follow-up for CUP (34.1 months) and OPX (27.8 months) pts were similar (P = 0.23). After matching, no significant differences were found between the two groups. The majority of pts fit the unfavorable HPV + risk category (73% CUP vs. 63% for OPX) while the remaining pts (27% CUP vs. 37% OPX) fit the favorable HPV+ category (P = 0.28). There were no significant differences between the CUP and OPX groups for 3yr DFS (89% vs. 81%; P = 0.94), and 3yr OS (91% vs. 91%; P = 0.11), respectively. Pts with T0N+M0 HPV-associated CUP have similar survival outcomes to matched pts with T1-2N+M0 HPV+ OPX. These pts should be included in clinical trials and risk stratified for de-intensification or intensification strategies based on their other known risk factors, such as nodal burden and smoking exposure.

Safety of pembrolizumab with chemoradiation (CRT) in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN).

6011 Background: Pembrolizumab (pembro) is a humanized monoclonal antibody that blocks the programmed death receptor-1 (PD-1) interaction with its ligands (PD-L1, PD-L2). While pembro is approved for platinum-refractory, recurrent/metastatic SCCHN, its role in definitive therapy for LA-SCCHN is not yet defined. Here we present the safety results of pembro with cisplatin-based CRT for patients (pts) with LA-SCCHN (NCT02586207). Methods: 27 pts with oropharyngeal (OP), hypopharyngeal (HP), and laryngeal (L) stage III-IVB SCCHN (any HPV status) eligible for cisplatin-based, definitive CRT were enrolled from November 2015 to August 2016 as part of a safety cohort. Pembro was given at a fixed dose of 200 mg IV 4-7 days prior to initiation of CRT and then every 3 weeks during CRT (2 concomitant doses) and then following CRT for 5 additional doses. CRT consisted of weekly cisplatin 40 mg/m2 IV x 6 doses (240 mg/m2 maximum) given concurrently with radiation at a dose of 2 Gy once daily for 35 fractions (total 70 Gy). Safety was determined by the occurrence of CRT or pembro dose-limiting adverse events (AEs) and immune-related AEs (irAEs). Efficacy was defined as complete response (CR) rate on imaging or with salvage surgery at 100 days post-CRT completion. Results: 20 (74%) pts with OP HPV+ and 7 (26%) pts with HPV- (4 L, 2 OP, 1 HP) tumors were enrolled. 21 (78%) completed all planned doses of pembro. 3 discontinued due to irAEs (G2 peripheral motor neuropathy, G3 AST elevation, G1 Lhermitte-like syndrome). 3 discontinued due to protocol reasons (early neck dissection -2 pts, prolonged hospitalization-1 pt). All pts completed the full radiation dose (70 Gy) without significant delay (defined as &gt; 5 days). 23 (85%) received the goal target dose of cisplatin (≥200 mg/m2). There was one pt death due to concurrent illness, unrelated to treatment. The study has been reopened with expansion cohorts of 34 HPV+ pts and 23 HPV- pts to evaluate efficacy. Conclusions: Pembro in combination with weekly cisplatin-based CRT is safe and does not significantly impair radiation or chemotherapy dosing. Efficacy of this combination is being explored further in this study and through larger phase III clinical trials. Clinical trial information: NCT02586207.

Impact of p16 expression on induction taxotere-cisplatin-5 FU (TPF) followed by cetuximab-radiotherapy in N2b-N3 head and neck squamous cell carcinoma (HNSCC): Results of GORTEC 2007-02 phase III randomized trial.

6070 Background: TPF is a reference induction chemotherapy regimen in non-operated locally advanced (LA) HNSCC. GORTEC 2007-02 phase III randomized trial was restricted to HNSCC patients with large nodal spread (N2b-N3). Results showed no benefit of 3 cycles of induction TPF followed by cetuximab-radiotherapy (RT), as compared to concurrent chemoradiotherapy (CRT) (Geoffrois et al ASCO 2016). Methods: Patients were randomized to receive concurrent CRT (arm A) or induction TPF followed by cetuximab-RT (arm B). RT was 70 Gy/35F/7 weeks. Concurrent chemotherapy was 3 cycles of carboplatin-5FU as previously described (Calais JNCI 1999). About 2/3 of patients had oropharyngeal cancers (OPC) and HPV status was determined in these patients using p16 expression as a surrogate (immunohistochemistry). Smoking status was also collected. Primary endpoint was progression free survival (PFS). Results: Between May 2009 and Aug 2013, 360 eligible patients were randomized including 231 (64%) OPC. Overall, p16 expression could be assessed in 172 / 231 OPC patients (74%) with 84 in arm A and 88 in arm B. 26 patients were found p16+ in arm A (31%) and 19 in arm B (22%). Only 8 out 45 (18%) p16+ patients were non-smokers showing that the large majority of OPC patients randomized were p16- (127/172) and smokers (117/129). A significant improvement in PFS was found in p16+ compared to p16- OPC (p &lt; 0.0001). The absence of benefit in PFS associated with TPF + cetux-RT compared with CRT was suggested both in p16+ (HR: 0.78, 95% CI: 0.28 – 2.20) and in p16- OPC (HR: 1.28, 95% CI: 0.84 – 1.93), and the interaction between p16 and treatment modality was not significant (p = 0.35). A significant benefit was observed in favor of arm B regarding distant metastasis, but this effect was not different between the p16+ and p16- OPC, while there was no benefit of TPF + cetux-RT compared with CRT for loco-regional control, regardless of p16 status. Conclusions: The OPC p16 subpopulations were small. No benefit of induction TPF chemotherapy followed by cetuximab-RT compared with CRT in OPC patients regardless of p16 status. Clinical trial information: NCT01233843.

Human papillomavirus first and second generation vaccines-current status and future directions.

It has been more than 10 years that the first prophylactic papillomavirus vaccine became available, although distribution has been mainly limited to the more affluent countries. The first two vaccines have been a great success, hundreds of millions of women and a much smaller number of men have been vaccinated ever since. In a few countries with high vaccination coverage, in particular Australia but also parts of Great Britain and others, clinical impact of vaccination programs is already visible and there are indications for herd immunity as well. Vaccine efficacy is higher than originally estimated and the vaccines have an excellent safety profile. Gardasil9 is a second generation HPV virus-like particle vaccine that was licensed in 2015 and there are more to come in the near future. Currently, burning questions in respect to HPV vaccination are the duration of protection - especially in regard to cross-protection - reduction of the three-dose regimen and its impact on cross-protection; and duration of response, as well as protection against oropharyngeal HPV infections. Furthermore, researchers are seeking to overcome limitations of the VLP vaccines, namely low thermal stability, cost, invasive administration, limited coverage of non-vaccine HPV types, and lack of therapeutic efficacy. In this review we summarize the current status of licensed VLP vaccines and address questions related to second and third generation HPV vaccines.

Oropharyngeal squamous cell carcinoma and HPV. Systematic review on overall management

Oral human papillomavirus infection amplifies the risk for oropharyngeal cancer. Human papillomavirus-associated cancers in otorhinolaryngology have typical characteristics. To improve understanding of management, therapy and prognosis of patients with oropharyngeal human papillomavirus-associated cancers a systematic review of the literature was reported. Medline, The Cochrane Library, Embase and Scielo electronic databases were searched. The search included published articles up to December 2006. A wide search strategy was employed in order to avoid publication biases and to assess studies in which the main aspects concerning oropharyngeal squamous cell carcinoma and human papillomavirus management are analyzed. A total of 120 articles were identified, of which 16 matched the inclusion criteria. Patients with human papillomavirus-associated oropharyngeal cancers have distinctive risk factors such as a high number of sex partners. They are typically younger, nonusers of tobacco and alcohol and have a better prognosis.