Safe Stop IPI-NIVO trial: early discontinuation of nivolumab upon achieving a complete or partial response in patients with irresectable stage III or metastatic melanoma treated with first-line ipilimumab-nivolumab - study protocol.

BACKGROUND: Patients with irresectable stage III or metastatic melanoma presenting with poor prognostic factors are usually treated with a combination of immune checkpoint inhibitors (ICIs), consisting of ipilimumab and nivolumab. This combination therapy is associated with severe immune related adverse events (irAEs) in about 60% of patients. In current clinical practice, patients are usually treated with ICIs for up to two years or until disease progression or the occurrence of unacceptable AEs. The incidence of irAEs gradually increases with duration of treatment. While durable tumour responses have been observed after early discontinuation of treatment, no consensus has been reached on optimal treatment duration. The objective of the Safe Stop IPI-NIVO trial is to evaluate whether early discontinuation of ICIs is safe in patients with irresectable stage III or metastatic melanoma who are treated with combination therapy. METHODS: The Safe Stop IPI-NIVO trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 80 patients with irresectable stage III or metastatic melanoma who are treated with combination therapy of ipilimumab-nivolumab and have a complete or partial response (CR/PR) according to RECIST v1.1 will be included to early discontinue maintenance therapy with anti-PD-1. The primary endpoint is the rate of ongoing response at 12 months after start of ICI. Secondary endpoints include ongoing response at 24 months, disease control at different time points, melanoma specific and overall survival, the incidence of irAEs and health-related quality of life. DISCUSSION: From a medical, healthcare and economic perspective, overtreatment should be prevented and shorter treatment duration of ICIs is preferred. If early discontinuation of ICIs is safe for patients who are treated with the combination of ipilimumab-nivolumab, the treatment duration of nivolumab could be shortened in patients with a favourable tumour response. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05652673, registration date: 08-12-2022.

Evaluation of a new two-step frailty assessment of head and neck patients in a prospective cohort.

PURPOSE: Assessing frailty, in head and neck cancer (HNC) patients is key when choosing appropriate treatment. Optimal screening is challenging, as it should be feasible and should avoid over-referral for comprehensive geriatric assessment (CGA) This study aims to evaluate the association between geriatric assessment using a new two-step care pathway, referral to geriatrician and adverse outcomes. METHODS: This institutional retrospective analysis on a prospective cohort analysed the multimodal geriatric assessment (GA) of newly diagnosed HNC patients. Uni- and multivariable logistic regression was performed to study the association between the screening tests, and referral to the geriatrician for complete geriatric screening, and adverse outcomes. RESULTS: This study included 539 patients, of whom 276 were screened. Patients who underwent the GA, were significantly older and more often had advanced tumour stages compared to non-screened patients. Referral to the geriatrician was done for 30.8% of patients. Of the 130 patients who underwent surgery, 26/130 (20%) experienced clinically relevant postoperative complications. Of the 184 patients who underwent (radio)chemotherapy, 50/184 (27.2%) had clinically relevant treatment-related toxicity. Age, treatment intensity, polypharmacy and cognitive deficits, were independently associated with referral to geriatrician. A medium to high risk of malnutrition was independently associated with acute radiation induced toxicity and adverse outcomes in general. CONCLUSION: The current study showed a 30.8% referral rate for CGA by a geriatrician. Age, treatment intensity, cognitive deficits and polypharmacy were associated with higher rates of referral. Furthermore, nutritional status was found to be an important negative factor for adverse treatment outcomes, that requires attention.

The effect of smell training on COVID-19 induced smell loss.

OBJECTIVE: while smell training appears to be effective for post viral smell loss, its effectiveness in COVID-19 induced smell loss is currently not well known. Therefore, we aim to investigate the potential effect of smell training on patients with COVID-19 induced smell loss. METHODS: we conducted a case-control study with two comparable cohorts. One of which (n=111) was instructed to perform smell training twice daily for 12 weeks, therapeutical adherence was monitored on a daily schedule, while the other cohort (n=50) did not perform smell training. The Sniffin' Sticks Test (SST) was used to objectify participants' sense of smell at baseline and after 12 weeks, reported as a Threshold, Discrimination, and Identification (TDI) score. We also determined the association between therapeutical adherence and the TDI scores. RESULTS: we found a significant difference in psychophysical smell function between patients with COVID-19 induced smell disorders who performed 12 weeks of smell training and those who did not. Median TDI difference between groups was 2.00 However, there was no association between the therapeutical adherence and olfactory function. CONCLUSION: we discovered a significant moderate difference in psychophysical smell function between patients with COVID-19-induced smell disorders who performed smell training and those who did not, implying a possible advantage of training. However, no relationship was found between therapeutical adherence of smell training and olfactory function.

Disentangling heterogeneity in contemporary undifferentiated arthritis - A large cohort study using latent class analysis.

OBJECTIVES: Undifferentiated arthritis(UA) is clinically heterogeneous and differs in outcomes ranging from spontaneous resolution to RA-development. Therefore, we hypothesized that subgroups exist within UA and we aimed to identify homogeneous groups based on clinical features, and thereafter to relate these groups to the outcomes spontaneous resolution and RA-development. These outcomes can only be studied in UA-patients in which DMARD-treatment does not influence the natural disease course; these cohorts are scarce. METHODS: We studied autoantibody-negative UA-patients (not fulfilling 1987/2010 RA-criteria, no alternate diagnosis), included in the Leiden Early Arthritis Clinic between 1993 and 2006, when early DMARD-treatment in UA was infrequent. Latent class analysis was used to identify subgroups based on combinations of clinical features. Within these subgroups, test-characteristics were assessed for spontaneous resolution of arthritis and RA-development within 1 year. RESULTS: 310 consecutive UA-patients were studied. Five classes were identified: location and number of swollen joints were most distinguishing. Classes were characterized by: 1) polyarthritis, often symmetric; 2) oligoarthritis, frequently with subacute onset; 3) wrist-monoarthritis, often with subacute onset, increased BMI and without morning stiffness; 4) small-joint monoarthritis, often without increased acute phase reactants, and 5) large-joint monoarthritis, often with subacute onset. Studying the classes in relation to the outcomes revealed that patients without spontaneous resolution (thus having persistent disease) were nearly absent in the classes characterized by monoarthritis (specificity >90%). Additionally, patients who developed RA were infrequent in monoarthritis classes (sensitivity <7%). CONCLUSION: Using a data-driven unsupervised approach, five subgroups within contemporary UA were identified. These have differences in the natural course of disease.

Is locally advanced head and neck cancer 'increasing' in the Netherlands? The paradox of absolute numbers, standardized incidence rates and proportional share.

BACKGROUND: Several reports have indicated that locally advanced head and neck cancer (LAHNC) has increased in the past decade. However, incidence trends cannot be easily compared because slightly different definitions of LAHNC were used. AIM: To investigate if the incidence of locally advanced disease (LAD) in the oral cavity, oropharynx, hypopharynx and larynx is indeed increasing over time, considering the growing and ageing population in the Netherlands. PATIENTS AND METHODS: Data were obtained from the Netherlands Cancer Registry (NCR). Primary head and neck squamous cell carcinomas of the oral cavity, oropharynx, hypopharynx and larynx diagnosed between 1989 and 2017 were included. Yearly numbers and European standardized incidence rates (ESRs) were reported by extent of disease. The annual percentage change (APC) over time in ESRs was calculated to assess trends. RESULTS: Absolute numbers and ESRs of LAD increased over time for oral cavity and most prominently for oropharynx carcinomas (before 1996, APC: 0.4, 95%CI: 0.1; 0.8 and APC: 5.7 (95%CI: 3.1; 8.4) after 1996: 1.5 (1.0; 2.0) respectively. For hypopharynx cancer the absolute number and ESR of LAD increased until 1997 and declined with 0.8% per year since 1997. Absolute numbers of patients with larynx cancer stayed stable over time, while ESR decreased (APC: -0.8 (95%CI: -1.1; -0.6)). CONCLUSION: The perception of an increasing trend in LAD in the Netherlands can be attributed to the increasing incidence of oral cavity and oropharynx carcinomas. For LAD of the hypopharynx a decreasing trend was observed. In larynx cancer, the proportional share of LAD of the larynx increased, even though incidence rates declined.

A population-based study of the epidemiology of oral squamous cell carcinoma in the Netherlands 1989-2018, with emphasis on young adults.

There has been an increasing trend in oral squamous cell carcinoma (OSCC) in patients under 45 years of age. The aim of this study was to evaluate the burden of OSCC in the Netherlands between 1989 and 2018 among young adults (age 20-34 years) when compared to adults (age 35-44 years), and to describe the burden in older groups as well, utilizing cancer registry data to characterize incidence patterns by age, sex, and risk factors. A total of 18,963 cases of OSCC were reported. The overall incidence rate, as measured by annual percentage change (APC), increased significantly from 1989 to 2010 by 1.3% per year (95% confidence interval (CI) 0.9-1.7%) but decreased thereafter by -0.9% (95% CI -2.5% to 0.7%). Annual incidence increased significantly by 2.4% (95% CI 1.1-3.8%) for patients aged 20-34 years, while it decreased for those aged 35-44 years by -0.9% (95% CI -1.7% to 0.0%). In patients older than 60 years, incidence rates increased overall (60-74 years: APC 1.8%, 95% CI 1.5-2.1%; ≥75 years: APC 1.5%, 95% CI 1.2-1.9%). Overall, 66.5% of patients were smokers and 65.3% were alcohol consumers. The marked differences in incidence within the young age subgroups warrants further investigation to elucidate any likely disparity in biological process and clinical outcomes in these populations.

Incidental findings during the diagnostic work-up in the head and neck cancer pathway: Effects on treatment delay and survival.

OBJECTIVES: As a result of the increasing number of diagnostic scans, incidental findings (IFs) are more frequently encountered during oncological work-up in patients with head and neck squamous cell carcinomas (HNSCC). IFs are unintentional discoveries found on diagnostic imaging. Relevant IFs implicate clinical consequences, resulting in delay in oncologic treatment initiation, which is associated with unfavorable outcomes. This study is the first to investigate the incidence and nature of IFs over the years and establish the effect of relevant IFs on delay. MATERIAL AND METHODS: This retrospective study compared two time periods (2010-2011 and 2016-2017), described associations between relevant IFs and delay in carepathway interval (days between first visit and treatment initiation) and assessed the effect of relevant IFs on overall two-year survival. RESULTS: In total, 592 patients were included. At least one IF was found in 61.5% of the patients, most frequently on chest-CT. In 128 patients (21.6%) a relevant IF was identified, resulting for the majority in radiologist recommendations (e.g. additional scanning). Presence of a relevant IF was an independent significant factor associated with delay in treatment initiation. The risk of dying was higher for patients with a relevant IF, although not significant in the multivariable model (HR: 1.46, p = 0.079). CONCLUSION: In diagnostic work-up for HNSCC patients, relevant IFs are frequently encountered. As the frequency of additional imaging rises over the years, the number of IFs increased simultaneously. These relevant IFs yield clinical implications and this study described that relevant IFs result in significant delay in treatment initiation.

Treating infections with ionizing radiation: a historical perspective and emerging techniques.

BACKGROUND: Widespread use and misuse of antibiotics have led to a dramatic increase in the emergence of antibiotic resistant bacteria, while the discovery and development of new antibiotics is declining. This has made certain implant-associated infections such as periprosthetic joint infections, where a biofilm is formed, very difficult to treat. Alternative treatment modalities are needed to treat these types of infections in the future. One candidate that has been used extensively in the past, is the use of ionizing radiation. This review aims to provide a historical overview and future perspective of radiation therapy in infectious diseases with a focus on orthopedic infections. METHODS: A systematic search strategy was designed to select studies that used radiation as treatment for bacterial or fungal infections. A total of 216 potentially relevant full-text publications were independently reviewed, of which 182 focused on external radiation and 34 on internal radiation. Due to the large number of studies, several topics were chosen. The main advantages, disadvantages, limitations, and implications of radiation treatment for infections were discussed. RESULTS: In the pre-antibiotic era, high mortality rates were seen in different infections such as pneumonia, gas gangrene and otitis media. In some cases, external radiation therapy decreased the mortality significantly but long-term follow-up of the patients was often not performed so long term radiation effects, as well as potential increased risk of malignancies could not be investigated. Internal radiation using alpha and beta emitting radionuclides show great promise in treating fungal and bacterial infections when combined with selective targeting through antibodies, thus minimizing possible collateral damage to healthy tissue. CONCLUSION: The novel prospects of radiation treatment strategies against planktonic and biofilm-related microbial infections seem feasible and are worth investigating further. However, potential risks involving radiation treatment must be considered in each individual patient.

Radioimmunotherapy of methicillin-resistant Staphylococcus aureus in planktonic state and biofilms.

BACKGROUND: Implant associated infections such as periprosthetic joint infections are difficult to treat as the bacteria form a biofilm on the prosthetic material. This biofilm complicates surgical and antibiotic treatment. With rising antibiotic resistance, alternative treatment options are needed to treat these infections in the future. The aim of this article is to provide proof-of-principle data required for further development of radioimmunotherapy for non-invasive treatment of implant associated infections. METHODS: Planktonic cells and biofilms of Methicillin-resistant staphylococcus aureus are grown and treated with radioimmunotherapy. The monoclonal antibodies used, target wall teichoic acids that are cell and biofilm specific. Three different radionuclides in different doses were used. Viability and metabolic activity of the bacterial cells and biofilms were measured by CFU dilution and XTT reduction. RESULTS: Alpha-RIT with Bismuth-213 showed significant and dose dependent killing in both planktonic MRSA and biofilm. When planktonic bacteria were treated with 370 kBq of 213Bi-RIT 99% of the bacteria were killed. Complete killing of the bacteria in the biofilm was seen at 185 kBq. Beta-RIT with Lutetium-177 and Actinium-225 showed little to no significant killing. CONCLUSION: Our results demonstrate the ability of specific antibodies loaded with an alpha-emitter Bismuth-213 to selectively kill staphylococcus aureus cells in vitro in both planktonic and biofilm state. RIT could therefore be a potentially alternative treatment modality against planktonic and biofilm-related microbial infections.

Budget impact analysis of introducing a non-reconstituted, hexavalent vaccine for pediatric immunization in the United Kingdom.

Objectives: Non-reconstituted, hexavalent vaccines (HV-NRs) can facilitate clinical practice by shortening vaccine preparation and administration time and by reducing the risk of vaccination errors compared to combination vaccines requiring reconstitution. The aim of this study was to determine the budget impact of introducing an HV-NR into the United Kingdom's (UK) pediatric immunization program, which currently uses a hexavalent vaccine requiring reconstitution (HV-R). Methods: Abudget impact model covering a 10-year time horizon was developed. The target population constituted closed UK birth cohorts from 2020 to 2029. Total direct costs from the payer's perspective consisted of four main categories: vaccine acquisition and management, healthcare provider's service provision, (non-)contaminated needle-stick and sharps injury (NSI), and non-NSI vaccination error costs. The net budget impact was calculated by comparing the costs in two different market share scenarios. Results: The use of HV-NR instead of HV-R was estimated to save £9,079,927 over a 10-year time horizon (i.e. £907,993 per year). Assuming all other vaccine criteria are equivalent the budget impact was most sensitive to changes in time spent by the healthcare provider and management costs. Conclusion: Results suggest, introducing an HV-NR into the UK's pediatric immunization program is potentially cost saving for the healthcare system.

High sensitivity and negative predictive value of sentinel lymph node biopsy in a retrospective early stage oral cavity cancer cohort in the Northern Netherlands.

OBJECTIVES: In cT1-2N0, oral squamous cell carcinoma (OSCC) occult metastases are detected in 23%-37% of cases. Sentinel lymph node biopsy (SLNB) was introduced in head and neck cancer as a minimally invasive alternative for an elective neck dissection in neck staging. Meta-analyses of SLNB accuracy show heterogeneity in the existing studies for reference standards, imaging techniques and pathological examination. The aim of this study was to assess the sensitivity and negative predictive value (NPV) of the SLNB in detecting occult metastases in cT1-2N0 OSCC in a well-defined cohort. DESIGN: Retrospective study. The SLNB procedure consisted of lymphoscintigraphy, SPECT/CT-scanning and gamma probe detection. Routine follow-up was the reference standard for the SLNB negative neck. Histopathological examination of sentinel lymph nodes (SLN) consisted of step serial sectioning, haematoxylin-eosin and cytokeratin AE1/3 staining. SETTING: Two comprehensive oncology centres. PARTICIPANTS: A total of 91 consecutive patients with primary cT1-2N0 OSCC treated by primary resection and neck staging by SLNB procedure between 2008 and 2016. MAIN OUTCOME MEASURES: Sensitivity and negative predictive value. RESULTS: In all cases, SLNs were harvested. A total of 25 (27%) patients had tumour-positive SLNs. The median follow-up was 32 months (range 2-104). Four patients were diagnosed with an isolated regional recurrence in the SLNB negative neck side resulting in an 85% sensitivity and a 94% NPV. CONCLUSION: In our cohort, the SLNB detected occult metastases in early OSCC with 85% sensitivity and 94% NPV. This supports that SLNB is a reliable procedure for surgical staging of the neck in case of oral cT1-2N0 SCC.

Age-specific incidence and treatment patterns of head and neck cancer in the Netherlands-A cohort study.

OBJECTIVES: To explore the incidence and treatment pattern of head and neck cancer in different age groups. DESIGN: Cohort study. SETTING: Netherlands Cancer Registry. PARTICIPANTS: All new primary head and neck cancer cases diagnosed between 2010 and 2014 were included and categorised into different age groups. MAIN OUTCOME MEASURES: Tumour site, stage, treatment modality, location of diagnosis and treatment. RESULTS: The study population was composed of 11 558 tumours. Oral cancer was the most common primary site (31%), followed by laryngeal (25%) and oropharyngeal cancer (22%). Ninety-six per cent of the entire study population was diagnosed and/or treated in a certified head and neck oncology centre which was lower in the 80+ population (92%). Multimodality treatment was less frequently applied with increasing age (eg oral cavity: 17% in 80+ vs 34% in 60-; P < .001). The percentage of patients not receiving tumour-directed treatment increased with age (eg oropharyngeal cancer: 25% in 80+ vs 6% in 80-; P < .001). CONCLUSIONS: This study confirms that less multimodal and tumour-directed treatment is applied with the increasing age of head and neck cancer patients.

Functional and effective whole brain connectivity using magnetoencephalography to identify monozygotic twin pairs.

Resting-state functional connectivity patterns are highly stable over time within subjects. This suggests that such 'functional fingerprints' may have strong genetic component. We investigated whether the functional (FC) or effective (EC) connectivity patterns of one monozygotic twin could be used to identify the co-twin among a larger sample and determined the overlap in functional fingerprints within monozygotic (MZ) twin pairs using resting state magnetoencephalography (MEG). We included 32 cognitively normal MZ twin pairs from the Netherlands Twin Register who participate in the EMIF-AD preclinAD study (average age 68 years). Combining EC information across multiple frequency bands we obtained an identification rate over 75%. Since MZ twin pairs are genetically identical these results suggest a high genetic contribution to MEG-based EC patterns, leading to large similarities in brain connectivity patterns between two individuals even after 60 years of life or more.

Survival of 86,690 patients with thyroid cancer: A population-based study in 29 European countries from EUROCARE-5.

BACKGROUND: Incidence rates of thyroid cancer (TC) increased in several countries during the last 30 years, while mortality rates remained unchanged, raising important questions for treatment and follow-up of TC patients. This study updates population-based estimates of relative survival (RS) after TC diagnosis in Europe by sex, country, age, period and histology. METHODS: Data from 87 cancer registries in 29 countries were extracted from the EUROCARE-5 dataset. One- and 5-year RS were estimated using the cohort approach for 86,690 adult TC patients diagnosed in 2000-2007 and followed-up to 12/31/2008. RS trends in 1999-2007 and 10-year RS in 2005-2007 were estimated using the period approach. RESULTS: In Europe 2000-2007, 5-year RS after TC was 88% in women and 81% in men. Survival rates varied by country and were strongly correlated (Pearson ρ = 75%) with country-specific incidence rates. Five-year RS decreased with age (in women from >95% at age 15-54 to 57% at age 75+), from 98% in women and 94% in men with papillary TC to 14% in women and 12% in men with anaplastic TC. Proportion of papillary TC varied by country and increased over time, while survival rates were similar across areas and periods. In 1999-2007, 5-year RS increased by five percentage points for all TCs but only by two for papillary and by four for follicular TC. Ten-year RS in 2005-2007 was 89% in women and 79% in men. CONCLUSIONS: The reported increasing TC survival trend and differences by area are mainly explained by the varying histological case-mix of cases.

Salivary gland pleomorphic adenoma in the Netherlands: A nationwide observational study of primary tumor incidence, malignant transformation, recurrence, and risk factors for recurrence.

INTRODUCTION: Whereas salivary gland pleomorphic adenoma (SGPA) is the most common type of salivary gland tumor, little is known about its epidemiology because national cancer registries do not register this disease. OBJECTIVES: To establish SGPA incidence trends, rates of secondary malignant transformation and recurrence and associated factors in the Netherlands. MATERIALS AND METHODS: Data on incidence, epidemiology, secondary malignant transformation and recurrence were retrieved from the Dutch pathology registry (PALGA) for the years 1992, 1997, 2002, 2007, and 2012. Multivariate analysis was performed to discover the risk factors for recurrence. RESULTS: 3506 cases of SGPA were recorded implying an overall European standardized rate of 4.2-4.9 per 100,000 person-years. Our figures showed a female preponderance (1:1.43) with an annual 1% rise in female incidence (95% confidence interval [CI]: 0.2-1.8) and a bimodal age distribution in women (p<0.0001). The overall 20-year recurrence rate was 6.7%, and median time to first recurrence was 7years. Positive and uncertain resection margins and younger age at diagnosis were risk factors for recurrence, with odds ratios (ORs) of 4.62 (95%CI 2.84-7.51), 4.08 (95%CI 2.24-7.43), and 0.42 (95%CI 0.29-0.63) respectively. Tumor locations in the minor salivary glands had lower odds of recurrence than tumors in the parotid (OR 0.24; 95% CI: 0.07-0.77; p<0.016). Malignant transformation occurred in 0.15% of SGPAs (3.2% of recurrences). CONCLUSION: This first nationwide study clearly showed sex differences in SGPA epidemiology, possibly suggesting some underlying hormonal mechanism. Long-term recurrence risks were low, and secondary malignant transformation risks were very low.

Variation in head and neck cancer care in the Netherlands: A retrospective cohort evaluation of incidence, treatment and outcome.

BACKGROUND: To explore variation in numbers and treatment between hospitals that treat head and neck cancer (HNC) in the Netherlands. MATERIAL AND METHODS: Patient, tumor and treatment characteristics were collected from the Netherlands Cancer Registry, while histopathological features were obtained by linkage to the national pathology record register PALGA. Inter-hospital variation in volume, stage, treatment, pathologically confirmed loco-regional recurrence and overall survival rate was evaluated by tumor site. RESULTS: In total, 2094 newly diagnosed patients were included, ranging from 65 to 417 patients in participating hospitals treating HNC in 2008. Oral cavity cancer was mainly treated by surgery only, ranging from 46 to 82% per hospital, while the proportion of surgery with (chemo)radiotherapy ranged from 18 to 40%. Increasing age, male sex, and high stage were associated with a higher hazard of dying. In oropharynx cancer, the use of (chemo)radiotherapy varied from 31 to 82% between hospitals. We found an indication that higher volume was associated with a lower overall hazard of dying for the total group, but not by subsite. Low numbers, e.g. for salivary gland, nasopharynx, nasal cavity and paranasal sinus, did not permit all desired analyses. CONCLUSION: This study revealed significant interhospital variation in numbers and treatment of especially oropharyngeal and oral cavity cancer. This study is limited because we had to rely on data recorded in the past for a different purpose. To understand whether this variation is unwanted, future research should be based on prospectively collected data, including detailed information on recurrences, additional case-mix information and cause of death.

Detection of HPV-associated oropharyngeal tumours in a 16-year cohort: more than meets the eye.

BACKGROUND: Accurate assessment of the prevalence of the human papilloma virus (HPV) in oropharyngeal tumours (OpSCC) is important because HPV-positive OpSCC are consistently associated with an improved overall survival. Recently, an algorithm has become available that reliably detects clinically relevant HPV in tumour tissue, however, no complete cohorts have been tested. The aim was to determine the prevalence of active high-risk HPV infection in a complete cohort of OpSCC collected over a 16-year period. METHODS: Using a triple algorithm of p16 immunohistochemistry, HPV-BRISH and HPV-PCR, we assessed the prevalence of active HPV infection in all OpSCC diagnosed in our hospital from 1997 to 2012 (n=193) and a random selection of 200 oral tumours (OSCC). RESULTS: Forty-seven OpSCC (24%) were HPVGP PCR-positive; 42 cases were HPV16+, 1 HPV18+, 3 HPV33+ and 1 HPV35+. Brightfield in situ hybridisation did not identify additional HPV-positive cases. Human papilloma virus-associated tumour proportion increased from 13% (1997-2004) to 30% (2005-2012). Human papilloma virus-positivity was an independent predictor for longer disease-specific survival (HR=0.22; 95%CI:0.10-0.47). Only one OSCC was HPV+. CONCLUSIONS: In our cohort, the incidence of HPV-associated OpSCC is low but increasing rapidly. The strict detection algorithm, analysis of disease-specific survival and the complete cohort, including palliatively treated patients, may influence the reported prevalence and prognostic value of HPV in OpSCC.

No evidence for a survival difference between upper and lower lip squamous cell carcinoma.

It is generally assumed that upper lip cancer has a worse survival than lower lip cancer, but this notion is not convincingly supported by limited literature. Therefore, we tested whether upper lip cancer has a worse survival than lower lip cancer. All primary squamous cell carcinoma (SCC) of the lip in the North-East of the Netherlands from 1989-2009 were extracted from the Netherlands Cancer Registry database. We calculated overall and relative survival rates. In this series of 979 lower lip and 126 upper lip SCC, men were 2.6 times more often affected, while the proportionate share of upper lip cancer was larger in women. The 5-year overall survival for lip cancer equaled 74% (95% confidence interval (CI) 70-77%), while the relative survival equaled 97% (95% CI 93-100%). The overall and relative 10-year survival rates were 51% (95% CI 47-54%) and 90% (95% CI 84-96%), respectively. The 10-year relative survival rate for patients with SCC of the upper lip was 94% (95% CI 74-111%) compared to 90% (95% CI 83-96%) for patients with SCC of the lower lip. There appears to be little evidence that patients with upper lip SCC have a worse survival rate.