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OBJECTIVE: Small-for-gestational-age (SGA) neonates, infants of diabetic mothers (IDM) and very-low-birth weight premature neonates (VLBW) are reported to have increased risk for developing iron deficiency and possibly associated neurocognitive delays. STUDY DESIGN: We conducted a pilot study to assess iron status at birth in at-risk neonates by measuring iron parameters in umbilical cord blood from SGA, IDM, VLBW and comparison neonates. RESULTS: Six of the 50 infants studied had biochemical evidence of iron deficiency at birth. Laboratory findings consistent with iron deficiency were found in one SGA, one IDM, three VLBW, and one comparison infant. None of the infants had evidence of iron deficiency anemia. CONCLUSIONS: Evidence of biochemical iron deficiency at birth was found in 17% of screened neonates. Studies are needed to determine whether these infants are at risk for developing iron-limited erythropoiesis, iron deficiency anemia or iron-deficient neurocognitive delay.

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BACKGROUND: Although several studies have documented adverse outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, data are inadequate for patients undergoing autologous (auto-)HSCT. METHODS: We conducted a retrospective cohort study of 300 consecutive patients receiving an auto-HSCT between 2006 and 2014. Patients had stool cultures for VRE on admission and weekly during hospitalization. RESULTS: Thirty-six percent of patients had VRE gastrointestinal (GI) colonization and 3% developed a VRE bloodstream infection (BSI), all of whom were colonized. VRE strain typing of BSI isolates showed that some patients shared identical patterns. Rates of colonization and BSI in colonized patients were similar to simultaneous patients undergoing allo-HSCT, except that the latter had a higher rate of colonization at admission. A diagnosis of lymphoma was associated with an increased risk of colonization. VRE BSI was associated with longer lengths of stay and possibly higher costs, but no decrease in overall survival, and colonized patients had no VRE infections during the year following discharge. Repeat stool cultures in patients subsequently undergoing allo-HSCT suggested that most, if not all, VRE-positive auto-HSCT patients lose their detectable GI colonization within a few months of discharge. CONCLUSION: VRE colonization is frequent but carries a low risk for infection in patients undergoing auto-HSCT. However, these patients can serve as reservoirs for transmission to higher risk patients. Moreover, patients may remain colonized if proceeding to an allo-HSCT shortly after auto-HSCT, potentially increasing the risk of the allogeneic procedure.

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OBJECTIVE: The American College of Obstetrics and Gynecology Committee on Obstetric Practice recently endorsed delayed cord clamping at preterm delivery. However, the committee report expressed the concern by some practitioners that delayed clamping or cord milking might induce hyperviscosity in preterm neonates. To address this issue we: (1) established reference ranges for whole-blood viscosity among preterm neonates (viscosity reference ranges had previously been reported only in term neonates) and (2) determined the effect of umbilical cord milking at deliveries <32 weeks gestation on subsequent blood viscosity measurements. STUDY DESIGN: This was a prospective study in two Neonatal Intensive Care Units. Blood viscosity was measured using a cone and plate viscometer. Associations were sought with gestation, hematocrit/hemoglobin and mean corpuscular volume. Reference ranges were determined for preterm infants <32 weeks gestation. Then, after umbilical cord milking at deliveries <32 weeks, viscosity was measured at birth and again during the 12 h after birth. In neonates with viscosities >95th % range, we sought signs of hyperviscosity (plethora, hypotonia, hypoglycemia, hyperbilirubinemia, thrombocytopenia). RESULT: Viscosity at higher and lower sheer rates were linearly related (n=32, r=0.971). Within the range of hematocrits measured (29-63%) viscosity correlated with hematocrit (r=0.877) and hemoglobin (r=0.853) but not with erythrocyte size (r=0.179). Viscosity was related to gestational age (n=58), primarily due to the lower hematocrits at lower gestational ages. In the 12 h after cord milking viscosity ranged from 3.1 to 9.5 centipoise. Three of twenty preterm, neonates had viscosities >95th % reference range. However, all values were well below those where hyperviscosity is defined in term neonates and all lacked features of hyperviscosity. CONCLUSION: Cord blood viscosity is directly proportional to hematocrit/hemoglobin, lower at early gestation and not associated with erythrocyte size. Cord milking at preterm delivery is associated with a low risk of clinical hyperviscosity. Practioners should not refrain from cord milking at preterm delivery because of a concern that it will commonly cause neonatal hyperviscosity.

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OBJECTIVE: On the day of birth, the bleeding time of very low birth-weight (VLBW, <1500 g) neonates is generally prolonged, compared with term neonates. However, their bleeding time generally improves (shortens) over the next 7 to 10 days. Ampicillin can prolong the bleeding times of term and late preterm neonates, but its effect on VLBW neonates, who already have a somewhat prolonged bleeding time initially, is not known. STUDY DESIGN: This was a prospective, single-centered, paired, before vs after test of the effect of ampicillin on template bleeding time and PFA-100 time (platelet function analyzer). Ampicillin was dosed at every 12 h intravenously, but decisions about discontinuation were made by the responsible clinician, independent of this study. RESULT: A total of 20 VLBW neonates were studied. They ranged from 23- to 30-weeks gestation at birth and weighed 500 t 1410 g. Initial bleeding times averaged 166 s (95% CI, 138 to 194) and initial PFA-100 times averaged 119 s (95% CI, 90 to 148). In all, 10 had ampicillin dosing stopped after a shorter course (4 to 7 doses) and 10 had it continued for a longer course (10 to 15 doses). Blood cultures were sterile in all 20, and no differences in laboratory or clinical features were found between those treated with a shorter vs longer course. After stopping the ampicillin following a short course the bleeding times and PFA-100 times were similar to the initial values. However, after a longer course the bleeding times were prolonged by an average of 2 min, to 284 s (95% CI, 242 to 326; P=0.001 vs initial). The PFA-100 times also trended longer by an average of 44 s (P=0.07). The number of doses of ampicillin received in the first week correlated with the degree of prolongation in bleeding time (r=0.68). CONCLUSION: Over the first week of life, a period when the bleeding time of VLBW neonates normally shortens, the opposite occurred (the bleeding time lengthened) if ≥ 10 doses of ampicillin were administered.

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X-Ray crystallography unequivocally determined the stereochemistry of the thymine base in the title compound, C(14)H(18)N(2)O(7). The absolute stereochemistry was determined from the use of d-ribose as the starting material. There are two independent mol-ecules in the asymmetric unit (Z' = 2) which exist as N-H⋯O hydrogen-bonded pairs in the crystal structure.

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There is an ongoing debate about the predictive value of histopathological parameters in oral cancer. In the past decades, the emphasis was on the possible added value of the so-called malignancy grading system. In a retrospective study on 128 previously untreated patients with a T1 or T2 squamous cell carcinoma of the tongue and the floor of the mouth, the value of the classical Broders' grading system and the malignancy grading system were compared with regard to various outcome measures such as regional metastasis, local recurrence and 5-year survival. The results show that neither of the histological grading systems has a strong predictive value and that none is superior to the other.

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OBJECTIVE: Several studies have indicated a correlation between the number of platelet transfusions received by newborn intensive care unit (NICU) patients and the mortality rate. The number of platelet transfusions might be a marker for level of illness, and thus predictive of mortality. However, an alternative hypothesis is that multiple platelet transfusions themselves are harmful in this population. STUDY DESIGN: We evaluated data from all thrombocytopenic neonates cared for in the Intermountain Healthcare NICUs in the past 4 years, seeking associations between the lowest platelet count recorded, number of platelet transfusions received and mortality rate. We also conducted a sensitivity analysis to examine the hypothesis that platelet transfusions were responsible for some fraction of the mortality rate. RESULT: Transfusion and outcome data were examined from 1600 thrombocytopenic NICU patients. At any level of platelet count, some patients received platelet transfusions but others did not. However, at all levels of platelet count, those that received platelet transfusions had a higher mortality rate. Neonates not given any platelet transfusions had a mortality rate of 2%, those with 1 or 2 transfusions had a mortality rate of 11% (P<0.001); those with >10 had a mortality rate of 35% (P<0.001); and those with > or = 20 had a mortality rate of 50% (P<0.001). A sensitivity analysis suggested that the platelet transfusions themselves were very likely responsible for some fraction of the increasing mortality rate. CONCLUSION: The number of platelet transfusions administered in the NICU predicts the mortality rate. Some of this correlation is ascribable to unknown and unmeasured factors such as level of illness. However, the present data and the sensitivity analysis both suggest that some of this correlation is due to harmful effects of multiple platelet transfusions in this group of patients.

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BACKGROUND: Small quantities of normal saline are sometimes instilled into the endotracheal tube of intubated neonates, to assist with the removal of thick secretions and maintain patency of the endotracheal tube. However, saline is detrimental to the innate immune system of the upper airway mucosa, rapidly unfolding and inactivating antimicrobial peptides such as LL-37. We previously reported the preparation and feasibility testing of 'ETCare', a low-sodium, physiologically based solution for airway care, and we now report results of a randomized, masked, controlled, two-centered study testing ETCare vs sterile saline among 60 intubated NICU patients. STUDY DESIGN: Sixty intubated NICU patients were randomized to having their airway care with ETCare vs saline. Three hypotheses were tested: (1) tolerance - patients will tolerate ETCare for airway care as well as they tolerate saline, (2) nosocomial infections - ETCare will result in fewer tracheal aspirates where organisms grow and fewer cases of nosocomial sepsis, and (3) chronic lung disuse - ETCare will result in fewer patients discharged home on supplemental O2. RESULTS: Thirty NICU patients with an endotracheal tube in place were randomized to receive their airway care with ETCare, and 30 to receive their care with saline. Only the pharmacist was aware of the randomization; the two solutions were visually indistinguishable and were dispensed in identical syringes. Tolerance of the solutions was similar. The ETCare recipients had trends toward fewer positive blood cultures (odds ratios (OR), 0.48; 95% confidence interval (CI), 0.13 to 1.68), and fewer discharges home on supplemental O2 (OR, 0.43; 95% CI, 0.14 to 1.32; P=0.075). CONCLUSIONS: On the basis of this study and our previous 10-patient feasibility trial, we maintain that, for airway care, intubated NICU patients tolerate ETCare as well as saline. Data from this study can be used in estimating the sample sizes needed for a phase III trial. We speculate that such a trial will demonstrate that, compared with saline, ETCare will result in fewer nosocomial infections and less chronic lung disease.

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The objective of this study is to retrospectively assess the clinical relevance, i.c. the event of a local recurrence, in patients surgically treated for tongue and floor of mouth squamous cell carcinoma when tumour cell are observed histopathologically at a distance of less than 0.5 cm. Furthermore, the pattern of invasion and the presence or absence of perineural spread were recorded. A total of 68 patients, surgically treated because of a tongue or floor of mouth squamous cell carcinoma, were examined. Patients in whom any degree of epithelial dysplasia was observed in the mucosal surgical margins had been excluded beforehand. Local recurrence occurred in 2 out of 30 patients with a free surgical margins >0.5 cm and in 3 out of 38 patients with a free surgical margin <0.5 cm, the difference being not statistically significant. Apparently, the presence of tumour cells within a distance of less than 0.5 cm, but not into the deep surgical margin, does not necessarily seem to require additional treatment. The pattern of invasion and the presence or absence of perineural spread were not significantly related with local recurrence either.

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INTRODUCTION: Reliable staging of the neck remains a diagnostic challenge in head and neck squamous cell carcinoma (HNSCC) patients. Monoclonal antibodies (MAbs) directed against tumour-associated antigens can be used for selective tumour targeting. When labelled with a gamma-emitting radionuclide like 99mTechnetium, such MAbs can be used for tumour detection by radioimmunoscintigraphy (RIS). OBJECTIVE: The aim of this study was to assess the potential of RIS for the detection of lymph node metastases in HNSCC patients. PATIENTS AND METHODS: In 49 patients with HNSCC, who were scheduled to undergo surgery including neck dissection, RIS using 99mTc-labelled squamous cell specific MAb E48 or U36 administered intravenously was compared with clinical palpation, computed tomography (CT), magnetic resonance imaging (MRI) and histopathological outcome. RESULTS: RIS detected lymph node metastases in 35 of 51 positive sides (sensitivity 69%). Interpretation of RIS was correct in 47 of 65 sides (accuracy 72%). Accuracy of palpation, CT and MRI were comparable. Immunohistochemical staining of lymph node metastases missed by RIS showed that the injected MAb had targeted these small tumour deposits but these were not visualized. CONCLUSIONS: RIS at its current stage of development is not superior to CT or MRI for the detection of lymph node metastases. As small tumour deposits were probably not visualized because of the limited sensitivity and/or spatial resolution of the gamma camera, positron emission tomography (PET) using MAbs labelled with positron emitters may improve the detection. As MAb-PET studies in an animal model showed promising results we will soon start a clinical MAb-PET study.

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An outbreak of methicillin-resistant Staphylococcus aureus (MRSA) occurred on a head and neck surgical (HNS) ward of a university hospital in Amsterdam. The outbreak lasted from May 2000 until November 2000, and MRSA spread to two intensive care units. Amplified fragment length polymorphism analysis indicated that a single clone was responsible for the outbreak. Phage-typing indicated that this clone was of a type that was uncommon in The Netherlands. Strict isolation of patients, according to the Dutch national guidelines, was instituted. During the outbreak, surveillance culture specimens, from patients, healthcare workers, and the environment, were obtained at regular intervals. MRSA was found in the dust filters of nebulizers through which air from the room was filtered and subsequently humidified. These nebulizers were used to humidify tracheostomies. The dust filters were not maintained according to the guidelines. Restricted use and cleaning and disinfection of all ultra-sonic nebulizers led to termination of the outbreak. The outbreak illustrates that to terminate transmission of outbreak strains of MRSA, meticulous measures are necessary, which not only include strict isolation precautions, but also decontamination of the environment. In addition, it demonstrates the necessity of adhering to cleaning and disinfection guidelines for all medical and nursing equipment used in the hospital.

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Lymphoscintigraphy for sentinel node (SN) detection has been studied extensively in melanoma and breast cancer. In head and neck squamous cell carcinoma (HNSCC), however, experience in this field is relatively meagre. The purpose of this study was to document and evaluate lymphoscintigraphic findings in HNSCC patients. Eighty-two patients with clinical T1-T4 N0 SCC of the oral cavity or oropharynx received peritumoral injections of 25-75 MBq 99mTc-colloidal albumin (CA). Dynamic lymphoscintigraphy was performed in lateral projection for 20 min, followed by 2 min static imaging in anterior projection. In 26 patients, additional static images were obtained 2-6 h after injection of the tracer. In four of 82 patients, both early and late imaging revealed no tracer transport. In 78 of 82 patients, one (60), two (14) or three (4) SNs could be visualized, either by dynamic scintigraphy (73) or delayed static imaging (5). In 48 of 78 (62%) patients, the SN was visualized within the first minute of dynamic imaging. In particular, SNs of tumours of the mobile tongue were visualized within the first minute. No effect of T-stage or 99mTc-CA dose on the transport time of the tracer towards the SN was seen. The distribution of the SNs in the various levels of the neck relative to the primary tumour sites within the oral cavity was in concordance with the patterns of lymph node metastases reported traditionally for patients with SCC in the oral cavity. This study demonstrates the different variables affecting SN identification with lymphoscintigraphy using 99mTc-CA in HNSCC patients.

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BACKGROUND: The clinical relevance of the presence of epithelial dysplasia in the margins of surgically removed oral squamous cell carcinoma is still unclear. METHOD: In a retrospective study, the presence of mild or moderate epithelial dysplasia in the surgical margins of tongue and floor of mouth squamous cell carcinoma was examined histologically. Patients with tumor cells within 0.5 cm of the surgical margins were excluded. Also patients with severe dysplasia were excluded, as this is usually regarded as carcinoma in situ. Patients that received postoperative irradiation were also excluded. Only patients who completed a follow-up period of five years were included. All together, a total number of 37 patients fulfilled the inclusion criteria. RESULTS: Epithelial dysplasia was observed in 7 out of the 37 patients. Five of these patients, and two of the 30 patients with no dysplasia, had a local recurrence (P < 0.01). CONCLUSION: The presence of mild or moderate epithelial dysplasia in the margins of surgically removed oral squamous cell carcinoma carries a significant risk for the development of local recurrence. However, it should be noted that this study was of a retrospective nature and that the group of patients with epithelial dysplasia in the surgical margins was rather small. On the other hand, the inclusion criteria were somewhat strict, by limiting the oral subsite to tongue/floor of mouth, by excluding patients in whom tumors cell were found within 0.5 cm of the surgical margins and by excluding patients who received postoperative radiotherapy, amongst others.

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BACKGROUND: This was a prospective study of the treatment of Frey syndrome, also known as gustatory sweating, with botulinum toxin A. METHODS: Thirteen patients with a mean involved skin area of 53 (range 36-80) cm2, as assessed with the Minor starch-iodine test, were treated with 0.1 ml toxin (75 units/ml) injected intracutaneously into every 4 cm2 of involved skin. The mean total dose was 100 (range 67.5-150) units. Treatment results were assessed every 3 months with the Minor test. The Frey Questionnaire Card (FQC) was used for subjective assessment. The mean follow-up after primary treatment was 20 (range 9-24) months. Treatment was repeated if the symptoms recurred. RESULTS: After 3 months 11 of the 13 patients showed a decrease of gustatory sweating of more than 90 per cent. All but one patient with a follow-up of 2 years suffered recurrent gustatory sweating. The mean recurrence-free period after primary treatment was 11 months and that after secondary treatment was 15 months. FQC score and objective assessment correlated well. Treatments were well tolerated, although two patients developed a temporary perioral muscle paresis. CONCLUSION: Botulinum toxin A produces good results in the treatment of Frey syndrome. Repeated treatment improves on the results of primary treatment.

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We retrospectively calculated the costs of head and neck oncology for reimbursement purposes. This analysis was based on 854 head and neck cancer patients treated between 1994 and 1996 in two major Dutch university hospitals. To anticipate future care costs, costs of required improvements in the quality of care were added. Costs of diagnosis, treatment and 2 years of follow-up of patients with a primary tumour were (euro) 21 858. For patients with a recurrent tumour, this amount was (euro) 27 629. The costs of 10 years of follow-up were (euro) 423 after discounting and correction for survival. In total, average costs per new patient were (euro) 31 829, which covered discounted costs of treating the primary tumour, costs of treating recurrent tumours in 40% of all patients and the costs of 10 years of follow-up. Costs of improving the quality of care were estimated to be (euro) 1598 per new patient.

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UNLABELLED: 186Re-labeled chimeric monoclonal antibody U36 (cMAb U36) was recently evaluated in a phase I dose escalation study in head and neck cancer patients. All 13 patients received 99mTc-labeled cMAb U36 before 186Re-cMAb U36 radioimmunotherapy. The aim of this study was to evaluate the suitability of multiple or limited blood sampling to predict clearance, red marrow absorbed dose, and myelotoxicity of 186Re-cMAb U36. METHODS: Population pharmacokinetics of 186Re-cMAb U36 were analyzed with a nonparametric expectation algorithm (NPEM 2) and used for Bayesian analysis of individual patient data to predict cMAb U36 clearance. RESULTS: 186Re-cMAb U36 clearance was most accurately predicted (r = 0.91, P < 0.001) with limited sampling for sample points 4 and 72 h after administration of 186Re-cMAb U36. These predictions were less accurate with 99mTc-cMAb U36 (r = 0.51, P = 0.078 for multiple sampling; r = 0.47, P = 0.104 for sampling at 4 and 21 h after administration). Thrombocytopenia was found to be correlated with the red marrow absorbed dose and was equally well predicted by limited blood sampling after administration of 99mTc-cMAb U36 (r = 0.81, P < 0.01) or 186Re-cMAb U36 (r = 0.79, P < 0.01). CONCLUSION: Limited sampling seems useful to predict pharmacokinetics and myelotoxicity of 186Re-cMAb U36.

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Isotretinoin (13-cis-retinoic acid, 13cRA) has proven to be active in chemoprevention of head and neck squamous cell carcinoma (HNSCC). Moreover, both all-trans-retinoic acid (ATRA) and 13cRA induce objective responses in oral premalignant lesions. After binding of retinoids to retinoic acid receptors (RARs and RXRs) dimers are formed that are able to regulate the expression of genes involved in growth and differentiation. We compared the metabolism and level of growth inhibition of 13cRA with that of ATRA, 9cRA and retinol in four HNSCC cell lines and normal oral keratinocyte cultures (OKC). These retinoid compounds are known to bind with different affinities to the retinoic acid receptors. We observed that all retinoids were similar with respect to their capacity to induce growth inhibition. One HNSCC line could be ranked as sensitive, one as moderately sensitive and the remaining two were totally insensitive; OKC were moderately sensitive. The rate at which the cells were able to catabolize the retinoid was similar for all compounds. Retinoid metabolism in HNSCC cells resulted in a profile of metabolites that was unique for each retinoid. These metabolic profiles were different in OKC. Our findings indicate that differences in retinoid receptor selectivity of these retinoids do not influence the level of growth inhibition and rate of metabolism.

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BACKGROUND: Despite improvements in locoregional treatment of stages III/IV squamous cell carcinoma of the head and neck (HNSCC), local and distant failure rates remain high. An effective adjuvant therapy is required for these patients. Among novel approaches is radioimmunotherapy, in which monoclonal antibodies (MAbs) are used for selective delivery of radiation to tumor cells. METHODS: The suitability of 186Re-labeled chimeric MAb U36 (186Re-cMAb U36) for radioimmunotherapy was evaluated in a phase I study, with radiation dose escalating steps of 11, 27, and 41 mCi/m2. Tumor targeting was monitored with a gamma camera, and the maximum tolerated dose was established in 13 patients with recurrent or metastatic disease. RESULTS: Administrations were well tolerated, and excellent targeting of tumor lesions was seen. Myelotoxicity was the only toxicity observed, resulting in dose-limiting toxicity in two patients treated with 41 mCi/m2. The MTD was established at 27 mCi/m2. A marked reduction in tumor size was observed in two patients, another showed stable disease for 6 months. CONCLUSIONS: Radioimmunotherapy with 186Re-cMAb U36 seems to be well tolerated, with bone marrow being the dose-limiting organ. The observation of antitumor effects is encouraging for further development of radioimmunotherapy for HNSCC.

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In 1953, Slaughter et al. [D. P. Slaughter et al., Cancer (Phila.), 6: 963-968, 1953] proposed the concept of field cancerization in patients with squamous cell carcinoma of the head and neck (HNSCC) and discussed its clinical significance for the development of second primary tumors and local recurrences. To define the process of field cancerization and its putative clinical implications, we analyzed genetic aberrations in HNSCC and the accompanying macroscopically normal mucosa. In 28 HNSCC patients, loss of heterozygosity was determined in tumor and five noncontiguous mucosal biopsies using eight microsatellite markers at 9p, 3p, and 17p. For patients who showed loss of heterozygosity in their mucosal biopsies, all margins of the surgical specimen were subsequently analyzed to determine the extension of the field. In these cases, additional markers at 8p, 13q, and 18q as well as p53 mutations were included to determine subclonal differences between field and tumor. Genetically altered fields were detected in 36% (10 of 28) of the HNSCC patients. The field varied in size between patients and consisted of genetically different subclones. In 7 of 10 cases, the field extended into the surgical margins. One particular patient with a genetically altered field in a surgical margin developed a local recurrence after 28 months of follow-up. Microsatellite analysis showed that this recurrence had more molecular markers in common with the nonresected premalignant field than with the original tumor, suggesting that this persistent field has progressed further into a new malignancy. Our data show that genetically altered mucosa remains after treatment in a significant proportion of HNSCC patients, which may explain in part the high frequency of local recurrences and second primary tumors. Adequate identification and risk assessment of these genetically altered fields may have profound implications for future patient management.

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High-risk human papillomaviruses (HPVs) have been proposed to be associated with a subset of head and neck cancers (HNSCCs). However, clear biological evidence linking HPV-mediated oncogenesis to the development of HNSCC is hardly available. An important biological mechanism underlying HPV-mediated carcinogenesis is the inactivation of p53 by the HPV E6 oncoprotein. In the present study we investigated this biological relationship between HPV and HNSCC. In total 84 HNSCC tumors were analyzed for the presence of high-risk HPV nucleic acids by DNA polymerase chain reaction-enzyme immunoassay (PCR-EIA) and E6 reverse transcriptase (RT)-PCR as well as for the presence of mutations in the p53 gene. We found 20/84 HPV16 DNA-positive cases with one or more DNA assays, 10 of which were consistently positive with all assays. Only 9/20 cases showed E6 mRNA expression, indicative for viral activity. Only these nine E6 mRNA-positive cases all lacked a p53 mutation, whereas both the other HPV DNA-positive and HPV-DNA negative tumors showed p53 mutations in 36% and 63% of the cases, respectively. Moreover, only in lymph node metastases of HPV E6 mRNA-positive tumors both viral DNA and E6 mRNA were present. Our study provides strong biological evidence for a plausible etiological role of high-risk HPV in a subgroup of HNSCC. Analysis of E6 mRNA expression by RT-PCR or alternatively, semiquantitative analyses of the viral load, seem more reliable assays to assess HPV involvement in HNSCC than the very sensitive DNA PCR analyses used routinely.

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