Papillomavirus and cancers: should we extend vaccination to boys in France?

Background: In 2006, the HPV (Human papillomavirus) 6/11/16/18 quadrivalent vaccine was approved by the European Medicines Agency and obtained its marketing authorization in both girls and boys. Currently, the French guidelines recommend and refund vaccination of girls aged 11 to 14 with a catch-up program for females from 15 to 19 years old. Discussion: In France, HPV vaccination coverage tends to decrease. At the end of 2015, the vaccination coverage with three doses reached only 14% in 16-year-old girls (three doses). Although men are also affected by HPV-related diseases such as anal cancer, ano-genital warts, penile cancer or upper aerodigestive tract cancer, vaccine recommendations in France are for girls only. To face the high prevalence of anal cancer and related diseases, the best option is vaccination. Moreover, by offering men a way to prevent diseases against which they do not have any protection yet, universal vaccination could better take into account the ethical issues of prevention. In this paper, we present the point of view of different medical specialties concerning the potential benefit of extending vaccination to boys. Conclusion: HPV vaccination of both genders could benefit from a better public acceptance and contribute to a better coverage, especially in countries with low vaccination rates.

Autologous myoblast transplantation for oculopharyngeal muscular dystrophy: a phase I/IIa clinical study.

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant genetic disease mainly characterized by ptosis and dysphagia. We conducted a phase I/IIa clinical study (ClinicalTrials.gov NCT00773227) using autologous myoblast transplantation following myotomy in adult OPMD patients. This study included 12 patients with clinical diagnosis of OPMD, indication for cricopharyngeal myotomy, and confirmed genetic diagnosis. The feasibility and safety end points of both autologous myoblast transplantation and the surgical procedure were assessed by videoendoscopy in addition to physical examinations. Potential therapeutic benefit was also assessed through videoendoscopy and videofluoroscopy of swallowing, quality of life score, dysphagia grade, and a drink test. Patients were injected with a median of 178 million myoblasts following myotomy. Short and long-term (2 years) safety and tolerability were observed in all the patients, with no adverse effects. There was an improvement in the quality of life score for all 12 patients, and no functional degradation in swallowing was observed for 10 patients. A cell dose-dependant improvement in swallowing was even observed in this study. This trial supports the hypothesis that a local injection of autologous myoblasts in the pharyngeal muscles is a safe and efficient procedure for OPMD patients.

Value of the cytological diagnosis in the treatment of parotid tumors.

OBJECTIVE: A cytological diagnosis is frequently used in the management of parotid tumor to distinguish benign from malignant tumors before surgery. The aim of this study was to evaluate the value of the cytological diagnosis in parotid tumors. STUDY DESIGN: Fine-needle aspiration cytology was performed in 110 patients undergoing a parotidectomy. The results were compared with the definitive histopathological findings, which are considered the standard diagnostic reference for comparative analysis. SETTING: University hospital. RESULTS: Correlation with histopathological results was observed in 83 (82.1%) cases. Discordance was observed in eight (8.2%) cases. The sensitivity and the specificity of the cytological diagnosis in the detection of malignant tumors were 67 and 96 percent, respectively. CONCLUSIONS: The cytological diagnosis performed in parotid tumors permits differentiation of a benign from a malignant tumor in the majority of cases; however, it underestimates the diagnosis of malignant tumors.

Clinical significance of micrometastases detection in lymph nodes from head and neck squamous cell carcinoma.

OBJECTIVE: Study the clinical relevance of micrometastases in head and neck squamous cell carcinoma (HNSCC). METHODS: We reviewed the outcome of 31 patients who underwent neck dissection for HNSCC with lymph node analysis by cytokeratin 19 real-time Taqman polymerase chain reaction (CK19RT-PCR) for detection of micrometastasis. Fifteen patients were N+ on histopathology (group 1) and 16 were N-; nine of these 16 patients were CK19RT-PCR positive (group 2), whereas seven were negative (group 3). Local and neck recurrences, metastases, and other tumour sites were recorded during follow-up. RESULTS: Five patients in group 1, eight patients in group 2, and one patient in group 3 experienced a tumor-related event. N- patients in groups 2 and 3 had a different outcome (P<0.01). CONCLUSION: It is suggested that CK19RTPCR detection of micrometastasis in lymph nodes could be of significant prognostic value in HNSCC, because more aggressive treatment could be indicated in these patients.

Impact of FDG-PET to detect recurrence of head and neck squamous cell carcinoma.

OBJECTIVE: Prospectively evaluate the impact of fluorodeoxyglucose-fluorine-18 positron emission tomography (FDG-PET) in the management of recurrence of advanced head and neck squamous cell carcinoma during the first year after treatment. STUDY DESIGN: Seventy patients were followed-up every 6 to 8 weeks during the first year after initial combined curative therapy. FDG-PET, together with conventional imaging and endoscopy were performed systematically at 1 year (group A) or prompted earlier in case of clinically suspicious recurrence (group B). The referring physician evaluated the impact of FDG-PET on the patient's management. Another clinician checked the pertinence of decisions. RESULTS: FDG-PET had a therapeutic impact in 8 of 43 group A patients and in 16 of 27 group B patients; the overall rate was 34%. This change was pertinent in 5 of 8 and 14 of 16 cases, respectively. Overall pertinence rate of decisions was 90% versus 70% without FDG-PET. CONCLUSIONS: FDG-PET had a significant overall therapeutic impact; the induced decisions were either pertinent or just led to "futile" noninvasive examinations. Systematic FDG-PET had a significantly lesser impact in comparison with FDG-PET motivated by clinical suspicion.

Estimation of the overall burden of cancers, precancerous lesions, and genital warts attributable to 9-valent HPV vaccine types in women and men in Europe.

BACKGROUND: In addition to cervical cancer, human papillomavirus (HPV) is responsible for a significant proportion of cancers and precancerous lesions of the vulva, vagina, anus, penis, head and neck, as well as genital warts. We estimated the annual number of new cases of these diseases attributable to 9-valent HPV vaccine types in women and men in Europe. METHODS: The annual number of new cancers of the cervix, vulva, vagina, anus, penis, and selected head and neck sites in the population of the European Medicines Agency territory was estimated based on age-specific incidence rates extracted from Cancer Incidence in 5 Continents, Volume X and Eurostat population data for 2015. The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated by applying the HPV attributable fraction from reference publications based on a large European multicenter study. For non-cervical cancers, HPV attributable fractions were based on oncogenically-active HPV infections only (i.e., detection of HPV DNA and either mRNA and/or p16 positivity). For precancerous lesions of the cervix, vulva, vagina, and anus, and for genital warts, previously published estimations were updated for the 2015 population. RESULTS: The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated at 47,992 (95% bound: 39,785-58,511). Cervical cancer showed the highest burden (31,130 cases), followed by head and neck cancer (6,786 cases), anal cancer (6,137 cases), vulvar cancer (1,466 cases), vaginal cancer (1,360 cases), and penile cancer (1,113 cases). About 81% were estimated to occur in women and 19% in men. The annual number of new precancerous lesions (CIN2+, VIN2/3, VaIN2/3, and AIN2/3) and genital warts attributable to 9-valent HPV vaccine types was estimated at 232,103 to 442,347 and 680,344 to 844,391, respectively. CONCLUSIONS: The burden of cancers associated with 9-valent HPV vaccine types in Europe is substantial in both sexes. Head and neck cancers constitute a heavy burden, particularly in men. Overall, about 90% of HPV-related cancers, 80% of precancerous lesions, and 90% of genital warts are expected to be attributable to 9-valent HPV vaccine types each year, demonstrating the important preventive potential of the 9-valent HPV vaccine in Europe.

Oculopharyngeal Muscular Dystrophy and Inherited Retinal Dystrophy in Bukhara Jews Due to Linked Mutations in the PABPN1 and NRL Genes.

AIM: We have previously described two unrelated Bukhara Jews (BJs) with a combination of oculopharyngeal muscular dystrophy (OPMD) and inherited retinal dystrophy (IRD), because of mutations in two linked genes: PABPN1 and NRL. Here we investigated the prevalence of the NRL mutation among BJs with OPMD. MATERIALS AND METHODS: PABPN1 and NRL mutation testing were performed by polymerase chain reaction amplification and direct sequencing on two cohorts of Bukhara Jewish patients: OPMD patients (with or without IRD) and IRD patients (without OPMD). RESULTS: Of 24 unrelated chromosomes from Bukhara Jewish OPMD patients, 19 (79%) harbored the NRL mutation. In contrast, the NRL mutation was not detected in Bukhara Jewish patients diagnosed with IRD but without OPMD. CONCLUSIONS: Our findings provide an explanation for the reoccurrence of IRD in Bukhara Jewish OPMD homozygotes. Moreover, they indicate that Bukhara Jewish OPMD patients are at high risk for carrying the NRL mutation, and should be offered appropriate genetic counseling and testing.

Premature proliferative arrest of cricopharyngeal myoblasts in oculo-pharyngeal muscular dystrophy: Therapeutic perspectives of autologous myoblast transplantation.

Cultures of myoblasts isolated from cricopharyngeal muscles from patients with oculopharyngeal muscular dystrophy (OPMD) have been performed to study the effect of the expanded (GCG)8-13 repeat, located on the poly(A) binding protein nuclear-1 (PABPN1), on satellite cell phenotype. Cell cultures exhibited a reduced myogenicity, as well as a rapid decrease in proliferative lifespan, as compared to controls. The incorporation of BrdU decreased during the proliferative lifespan, due to a progressive accumulation of non-dividing cells. A lower fusion index was also observed, but myoblasts were able to form large myotubes when OPMD cultures were purified, although a rapid loss of myogenicity during successive passages was also observed. Myoblasts isolated from unaffected muscles did not show the defects observed in cricopharyngeal muscle cultures. The PABPN1 was predominantly located in nuclei of myoblasts and in both the nuclei and cytoplasm of myotubes in OPMD cultures. In vivo analysis of OPMD muscles showed that the number of satellite cells was slightly higher than that observed in age matched controls. Mutation of the PABPN1 in OPMD provokes premature senescence in dividing myoblasts, that may be due to intranuclear toxic aggregates. These results suggest that myoblast autografts, isolated from unaffected muscles, and injected into the dystrophic pharyngeal muscles, may be a useful therapeutic strategy to restore muscular function. Its tolerance and feasibility has been preclinically demonstrated in the dog.

Long-term results of cricopharyngeal myotomy in oculopharyngeal muscular dystrophy.

OBJECTIVE: To analyze long-term results of extramucosal cricopharyngeal myotomy in oculopharyngeal muscular dystrophy. STUDY DESIGN: The preoperative and postoperative evaluations including symptoms, type of feeding, weight, and functional examinations were retrospectively evaluated in 39 patients. Results were defined postoperatively as successful, partial, or failed. SETTING: University hospital. RESULTS: In the short term, 25 patients showed a complete remission of symptoms, 10 showed a marked improvement, and 4 exhibited no improvement at all (success rate of 90%). Long-term evaluation during a mean follow-up of 4 years showed that of the 35 improved patients, 12 exhibited a recurrence of dysphagia (mean time of 39 months). In 3 of these 12 patients, a revision transmucosal endoscopic cricopharyngeal myotomy was performed with a successful outcome in 2. Of the 4 patients who initially showed no improvement, 1 was improved by transmucosal myotomy. CONCLUSION: Extramucosal cricopharyngeal myotomy improves dysphagia in oculopharyngeal muscular dystrophy patients during the first few years but one third of the patients exhibited a recurrence of symptoms within 3 years. Revision by transmucosal endoscopic myotomy may be performed. EBM RATING: C-4.

Reappraisal of metastatic lymph node topography in head and neck squamous cell carcinomas.

OBJECTIVE: To analyze the lymphatic distribution of metastatic carcinomatous cells in cervical lymph nodes in head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN AND SETTING: We retrospectively reviewed 119 patients treated in our hospital for HNSCC (1999-2004). Topography of the neck dissection specimens was prospectively classified according to the classification of Robbins. The 4000 lymph nodes were analyzed by optical microscopy using hematoxylin-eosin-safran (HES) staining. In cases of negative results in level II, cytokeratin (AE1/AE3) immunodetection was performed. RESULTS: Metastases were visualized using HES in 6.4% of lymph nodes for oral cavity, and 4.7% of oropharyngeal, 4.4% of hypopharyngeal, and 1.3% of endolaryngeal cancers. The highest incidence of nodal metastasis was observed in level IIa (P < 0.01). In eight patients (6.7%) with lymph node metastases, level II was spared. In these patients, all 134 nodes histologically negative on HES were confirmed to be negative by IHC. CONCLUSIONS: Level IIa is the main level involved in regional metastases of HNSCC, regardless of the primary site of cancer. However, in eight (6.7%) patients, level II was spared, as confirmed by IHC. In these cases, level II did not represent the first step of drainage from the tumor. The sentinel lymph node technique in HNSCC is discussed in light of these results.

[Current trends in diagnosis and treatment head and neck cancer]. / Approches diagnostiques et thérapeutiques actuelles des adénopathies des carcinomes des voles aérodigestives supéieures .

Prognosis of head and neck squamous cell carcinomas (HNSCC) is partly determined by lymph nodes metastases. Contemporary imaging provides detection of adenopathies but remains unable to detect infracentimetric micrometastatic nodes. Topographical classification according to Robbins allows for better treatment through proper definition of impaired neck areas. The high rate of node metastases in HNSCC indicates systematic treatment of the neck in most localizations. Several neck dissection techniques are available with wide acceptation of elective functional neck dissections. Improvement of detection of node metastases and better selection of neck sites for treatment are eventual direction of progress. In neck carcinoma with unknown primary, search of primary should address first head and neck area and upper aero-digestive tract. Differential diagnosis are glomic tumour, congenital cyst and other causes of lymph node disease

Usefulness of combination of high-resolution ultrasonography and dual-phase dual-isotope iodine 123/technetium Tc 99m sestamibi scintigraphy for the preoperative localization of hyperplastic parathyroid glands in renal hyperparathyroidism.

BACKGROUND: The usefulness of both dual-phase dual-isotope iodine 123 ( 123 I)/technetium Tc 99m ( 99m Tc) sestamibi scintigraphy and ultrasonography for the detection of hyperplastic parathyroid glands secondary to renal hyperparathyroidism is rarely addressed; most studies focus on primary hyperparathyroidism. However, it may be crucial to identify and accurately localize hyperplastic glands before surgery. METHODS: To study the usefulness of high-resolution ultrasonography (performed by both the radiologist and surgeon) and dual-phase dual-isotope 123 I/ 99m Tc sestamibi scintigraphy in patients with renal hyperparathyroidism, a series of 20 patients consecutively referred for parathyroidectomy was studied prospectively. Results of both examinations, independently scored, were correlated with surgical and histopathologic findings for each hyperplastic parathyroid gland localization. RESULTS: All parathyroid glands except 1 were found during primary surgery consisting of a subtotal parathyroidectomy (success rate, 99%). The missed gland was removed successfully 1 month later. Neither supernumerary nor ectopic glands were found. Mean weight of totally removed parathyroid glands was 633 mg. Ultrasonography detected 75% of hyperplastic parathyroid glands; dual-phase 123 I/ 99m Tc sestamibi scintigraphy, 66%; and a combination of both, 88%. Most missed glands at scintigraphy corresponded to superior glands, whereas false-negative results at ultrasonography correlated with low gland weight. CONCLUSION: Combined ultrasonography and 123 I/ 99m Tc sestamibi scintigraphy should be considered for routine use to localize hyperplastic parathyroid glands in patients with renal hyperparathyroidism undergoing surgery. We suggest performing scintigraphy first, before ultrasonography, to guide the radiologist to areas of hyperfunctioning glands. In our experience, this proved very helpful in achieving a high surgical success rate in patients with renal hyperparathyroidism, especially when the surgeon visualizes the parathyroid glands at ultrasonography.

Facial nerve dysfunction after parotidectomy: the role of local factors.

OBJECTIVES/HYPOTHESIS: The objective was to analyze the incidence and factors associated with facial nerve dysfunction after conservative parotidectomy with facial nerve dissection. STUDY DESIGN: A retrospective unicentric study in a tertiary care center with prospective record of studied factors. METHODS: Over a 10-year period, 131 patients with normal facial nerve function underwent a superficial or total conservative parotidectomy with nerve dissection performed by one surgeon for primary benign or malignant tumors. Facial nerve function was assessed on the first postoperative day and at 1 month and 6 months after the parotidectomy. Extent of surgery, histopathological findings, tumor size, close contact of tumor with facial nerve, and sex and age of the patient were reviewed. These variables were studied in a chi2 statistical univariate and stratified analysis to determine their association with postoperative facial nerve dysfunction. RESULTS: Incidence of postoperative facial nerve dysfunction was 42.7% on the first postoperative day, 30.7% at 1 month after the parotidectomy, and 0% at 6 months after the parotidectomy. The most common dysfunction was paresis in a single nerve branch (48.2%), in particular, the marginal mandibular branch. Total parotidectomy was associated with a significantly higher incidence of facial nerve dysfunction during the first postoperative period (60.5% at day 1 and 44.7% at month 1) than superficial parotidectomy (18.2% at day 1 and 10.9% at month 1) (P < .001). In patients with total parotidectomy, close contact of the tumor with the facial nerve was found to have statistical causal relation with facial nerve weakness. In patients with superficial parotidectomy, inflammatory conditions were found as factors that increased postoperative facial nerve dysfunction. CONCLUSION: In the study series of conservative parotidectomies with facial nerve dissection, only extent of surgery and particular local conditions of nerve dissection, especially the close contact of tumor with facial nerve and inflammatory conditions, were found to be associated with postoperative facial nerve dysfunction.

Role of medialization in the improvement of breath control in unilateral vocal fold paralysis.

A prospective study was performed on 18 adults to analyze disturbances of voice and respiratory function in unilateral vocal fold paralysis and the role of medialization in the improvement of breath control. In addition to physical examination, an acoustic and aerodynamic analysis, as well as patient self-assessment, were performed both before and after medialization (14 fat injections, 4 thyroplasties) to evaluate voice and both phonatory breath control and respiratory function outcome. Preoperative and postoperative results, at short, middle, and long term, were compared to data from 14 control subjects and evaluated by statistical analysis. Preoperative acoustic and aerodynamic parameters were significantly disturbed in comparison to controls. Independently of the pulmonary status, medialization induced an improvement in most of the parameters at short and long terms, whereas a diminished effect was observed at middle term. Phonatory breath control, as evaluated by maximum phonation time, mean flow rate, and expired volume, was statistically improved, with the best results being obtained in women. From the questionnaire, it was clear that voice, as well as phonatory breath control and respiratory function, showed considerable improvement, although some difficulties persisted during effort. This study demonstrates that there is a disturbance of phonatory breath control and respiratory function in adult unilateral vocal fold paralysis. Improvement following medialization supports the concept that the respiratory dysfunction seen beforehand is most probably the result of air escape rather than laryngeal obstruction. Although medialization may provoke an extrathoracic obstruction, its feature of variability appears to improve breath control.

A predictive transcriptomic signature of oropharyngeal cancer according to HPV16 status exclusively.

OBJECTIVE: Human-papillomaviruses (HPV) type 16 is a causative agent in an increasing subset of oropharyngeal squamous cell carcinomas (OPSCCs). These tumors have distinct oncogenic mechanisms and a more favorable prognosis than tobacco-induced OPSCCs. Although these differences emphasize the need for a specific therapeutic approach, HPV status is still not used to guide treatment. A better characterization of the molecular profile related to HPV16-induced OPSCC might help to develop personalized treatments. PATIENTS AND METHODS: Using a human whole-genome DNA-microarray, we have examined the gene expression profiles in 15 HPV-negative and 15 transcriptionally-active HPV-positive OPSCCs. The study was conducted in two steps. Firstly, a learning/training-set consisting of 8 HPV16-positive and 8 HPV16-negative OPSCCs was analyzed to identify a specific signature. Potentially confounding factors (stage, sex and tobacco) were equally distributed in both groups. Subsequently the robustness of this signature was confirmed by blind case-by-case classification of a validation-set composed of the 14 remaining tumors. RESULTS: We have identified a signature composed of 224 genes, which discriminates HPV16-induced OPSCC from their HPV-negative counterparts. After the blind classification of the 14 tumours, the viral status was revealed: 13 out of 14 tumors were correctly classified according to tumor etiology, 1/14 was not determined and none were misclassified. Several of the differentially expressed genes were involved in cell-cycle regulation, DNA replication and repair, transcription regulation, immune response and apoptosis. CONCLUSION: Our study contributes to a better understanding of pathogenic mechanisms involved in the development of HPV-positive OPSCCs and in the identification of potential therapeutic targets.

Hypofractionated palliative radiotherapy for advanced head and neck cancer: the IHF2SQ regimen.

BACKGROUND: Standard treatment for unresectable advanced head and neck squamous cell carcinoma is chemoradiotherapy, which can be toxic, particularly among patients with coexisting medical conditions. We report our experience with the hypofractionated radiotherapy regimen Irradiation HypoFractionnée 2 Séances Quotidiennes (IHF2SQ). METHODS: We retrospectively reviewed 78 patients treated with the IHF2SQ regimen. Radiotherapy was administrated as 2 fractions of 3 Gy per day (days 1 and 3), during the first, third, fifth, and seventh week of treatment with concurrent platinum-based chemotherapy. RESULTS: Tolerance was excellent. Forty-one patients had complete or partial response. Median overall survival (OS) was 12.9 months and median progression-free survival (PFS) was 10.3 months. One-year OS, specific survival (SS), and PFS were 58%, 71%, 51.5%, respectively. Independent predictive factors increasing the PFS were response to chemoradiotherapy, male sex, and laryngeal tumor location. CONCLUSIONS: This regimen is an alternative to conventional chemoradiotherapy with good response rates and acceptable toxicity for selected patients.

Oropharyngeal cancers: significance of HPV16 detection in neck lymph nodes.

BACKGROUND: An increasing proportion of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with human papillomavirus (HPV) type 16 infection. Several authors have suggested that HR-HPV DNA could be used as a marker of metastases in cervical cancers. Although HPV16 DNA has been detected in neck lymph node (LN) metastases of HPV16-positive OPSCC, its significance remains controversial. Does this presence correlate to metastatic involvement or is it just the consequence of LN filter function? OBJECTIVES: This study aims to analyse the relationship between HPV16 detection in neck LNs of HPV16-positive OPSCC and their pathological status. STUDY DESIGN: HP16-viral load (VL) was quantified by real-time-polymerase-chain reaction in primary tumours and neck LNs, in 11 patients with HPV16-positive OPSCC and in three patients with HPV16-negative OPSCC. HPV16 in situ hybridisation and p16 immunohistochemistry were performed in all LNs. RESULTS: A total of 45 LN levels were assessed. HPV16 DNA was not identified in HPV16-negative OPSCC LNs. All metastatic LNs from HPV16-positive OPSCC had a high VL and the viral DNA was located within tumoural cells. Among 27 pathologically tumour-free LN (PTFLN) levels 16/27 had no detectable VL, whereas the VL was low or medium (<10(5)copies/million cells) in 8/27 and high (>10(5)copies/million cells) in 3/27 PTFLN. In the latter group, no metastatic cell was identified and the viral DNA was located in immune cells. CONCLUSION: HPV16 detection in LN is explained by its presence within either metastatic cells or immune cells. HPV16 detection in PTFLN is not necessarily correlated to occult LN metastases.

Human papillomavirus type 16 oropharyngeal cancers in lymph nodes as a marker of metastases.

BACKGROUND: Oropharyngeal squamous cell carcinomas (OSCCs) are associated with high-grade human papillomavirus (HPV) infection in 20% to 30% of cases. HPV-16 DNA has been detected in cervical lymph node metastases of HPV-16(+) OSCC. However, the meaning of HPV-16 DNA detection in lymph nodes remains controversial. Does the presence of HPV-16 DNA in lymph nodes correlate with their metastatic involvement, or is it just a consequence of the filter function of lymph nodes? METHODS: Viral load quantification using reverse transcriptase-polymerase chain reaction was retrospectively performed in primary tumors and in cervical lymph nodes, originating from levels IIa, IIb, and III, in 11 patients with HPV-16(+) OSCC and in 3 control patients with HPV-16(-) OSCC. RESULTS: A total of 45 lymph node levels were analyzed. HPV-16 DNA was not detected in HPV-16(-) OSCC lymph nodes. No statistically significant difference was found between primary tumors and metastatic lymph nodes viral load (P > .01). The viral load value was significantly higher in metastatic lymph nodes than in tumor-free lymph nodes (P < .01). Among 27 tumor-free lymph node levels, the viral load value was undetectable in 16, low or medium (<10(5) copies per million cells) in 8, and high (>10(5) copies per million cells) in 3. CONCLUSIONS: HPV-16 DNA detection in lymph nodes of patients affected with HPV-16(+) oropharyngeal cancer is indicative of metastatic involvement. Tumor-free lymph nodes with a high viral load value would suggest the presence of occult lymph nodes metastasis and the opportunity to use HPV-16 DNA as a metastatic marker. Further investigations are needed.

Human papillomavirus genotype distribution in oropharynx and oral cavity cancer in France--The EDiTH VI study.

BACKGROUND: The incidence of oropharyngeal cancers has gradually increased over the last decades. Recent studies suggest an association between human papillomavirus (HPV) infection and several head and neck cancers, especially oropharyngeal and oral cavity invasive carcinomas. OBJECTIVES: The objective was to assess the overall and type specific HPV prevalence in oropharyngeal and oral cavity carcinomas in France. STUDY DESIGN: Paraffin-embedded tumour specimens were retrospectively collected in 12 French centres and centrally tested for HPV detection and genotyping (INNO-LiPA assay). RESULTS: A total of 523 cases (77% males) were collected, among which 60% were oropharyngeal and 40% oral cavity carcinomas. The most frequent anatomical sites were tonsil (58.9%) and base of tongue (13.7%) for the oropharynx and floor of mouth (41.1%) and oral tongue (38.3%) for the oral cavity. Overall HPV prevalence was 46.5% in oropharyngeal carcinomas and 10.5% in oral cavity carcinomas and was higher in female than in male cases (63.5% vs 42.2% in oropharynx and 17.2% vs 8.0% in oral cavity). About 95% of HPV-positive cases were infected by a single HPV type. HPV 16 was the most prevalent type and was found in 89.7% and 95.5% of HPV-positive oropharyngeal and oral cavity carcinoma cases, respectively. All other HPV types had prevalence below 5%. CONCLUSIONS: Our results indicate that HPV is common among oropharyngeal and oral cavity carcinoma cases in France and emphasize the predominance of HPV 16. The potential benefit of HPV vaccination on the occurrence of head and neck carcinomas should be further evaluated.