[Show abstract][Hide abstract] ABSTRACT: Purpose
Human papillomavirus (HPV) 16 infection is associated with oropharyngeal carcinogenesis and is likely the cause of the reported increase in disease incidence. We evaluated the prevalence of HPV infection and the reliability of different diagnostic tools using primary tumor samples from a cohort of 50 patients.
Methods and Materials
Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected from all 50 consecutive primary oropharyngeal SCC patients who were enrolled in the study; fresh tumor samples were available in 22 cases. NucliSENS EasyQ HPVv1 was used for RNA, and Digene Hybrid Capture-2(HC2) was used for DNA detection. p16 Expression was evaluated by immunohistochemistry in FPPE specimens.
Based on the DNA detection assay on FFPE samples, the frequency of high-risk HPV infection was 32%. The agreement rate between HPV RNA and HPV DNA detection in fresh samples was 100%. The agreement rate between p16 immunohistochemistry (IHC) and the detection of HPV DNA in the FFPE samples was fair but not excellent (κ = 0.618). HPV DNA detection was highly significant, as measured by disease-specific survival and determined using a Wilcoxon test (P=.001). p16 IHC also exhibited a prognostic value but with a lower statistical significance (P=.0475). The detection of HPV DNA, but not p16 IHC, was also significantly correlated with locoregional control (P=.0461).
Diagnostic methods based on the detection of HPV nucleic acids appear to be more reliable and objective because they do not require reading by a trained histopathologist. Furthermore, the detection of HPV DNA exhibits an improved correlation with survival, and therefore appears definitely more reliable than p16 IHC for routine use in clinical practice.
International journal of radiation oncology, biology, physics 08/2014; 89(5):1115–1120. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several studies in the last decade evaluated conservative surgical procedures, and in particular supracricoid operations, as an alternative to total laryngectomy for the salvage of recurrences of laryngeal SCC after a first attempt of organ preservation.
The clinical records of 68 consecutive patients, primarily treated by irradiation or endoscopic surgery, and surgically salvaged by total laryngectomy or supracricoid partial laryngectomy in two large University hospitals in Italy from 2004 to 2010, were reviewed.
the survival was not affected by the primary treatment or by salvage modality. The only parameter always keeping a prognostic value is the involvement of resection margins of salvage surgery. Patients with early relapse seems to have a worse prognosis than patients with a delayed relapse (p=0.05 at Cox multivariate analysis, p=0.048 at Wilcoxon test, for overall survival from the primary treatment).
Supracricoid operations, if the indications are careful, can prove reliable salvage procedures. Head Neck, 2013.
[Show abstract][Hide abstract] ABSTRACT: Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is an entity with peculiar clinical and molecular characteristics, which mainly arises from the reticulated epithelium lining the crypts of the palatine tonsils and the base of the tongue. The only head and neck site with a definite etiological association between persistent high-risk (HR) HPV infection and development of SCC is the oropharynx. HPV-positive malignancies represent 5-20% of all HNSCCs and 40-90% of those arising from the oropharynx, with widely variable rates depending on the geographic area, population, relative prevalence of environment-related SCC and detection assay. HPV-16 is by far the most common HR HPV genotype detected in oropharyngeal SCC (OPSCC), and the only definitely carcinogenic genotype for the head and neck region. Patients with HPV-induced OPSCC are more likely to be middle-aged white men, non-smokers, non-drinkers or mild to moderate drinkers, with higher socioeconomic status and better performance status than subjects with HPV-unrelated SCC. HPV-induced HNSCCs are often described as non-keratinizing, poorly differentiated or basaloid carcinomas, and are diagnosed in earlier T-category with a trend for a more advanced N-category, with cystic degeneration, than the HPV-unrelated carcinomas. HPV positivity is associated with better response to treatment and modality-independent survival benefit. Treatment selection in HPV-related oropharyngeal carcinoma is becoming a critical issue, and although there is no evidence from randomized, controlled trials to support a treatment de-escalation in HPV-positive SCC, some investigators argue that intensive combined modality strategies may represent an overtreatment.
Acta otorhinolaryngologica Italica: organo ufficiale della Società italiana di otorinolaringologia e chirurgia cervico-facciale 04/2013; 33(2):77-87. · 0.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:Human papillomavirus 16 infection has been proven to be associated with oropharyngeal squamous cell carcinomas (SCCs) and is probably the main reason of the reported increase in the incidence. The role of high-risk (HR) HPV for carcinogenesis of other sites in the head and neck awaits confirmation. With the aim to evaluate the prevalence of HPV infection and the reliability of different diagnostic tools in SCCs of different sites, 109 consecutive untreated head and neck SCCs were enroled, and fresh tumour samples collected.Methods:Human papillomavirus DNA was detected by Digene Hybrid Capture 2 (HC2). Human papillomavirus E6 and E7 mRNA were detected by NucliSENS EasyQ HPVv1. P16 expression was evaluated by immunohistochemistry.Results:In all, 12.84% of cases were infected by HR genotypes and 1.84% by low-risk genotypes. Human papillomavirus 16 accounted for 87% of HR infections. The overall agreement between DNA and RNA detection is 99.1%. Although p16 expression clearly correlates with HPV infection (P=0.0051), the inter-rater agreement is poor (k=0.27). The oropharynx showed the highest HR HPV infection rate (47.6%) and was also the only site in which p16 immunohistochemistry revealed to be a fair, but not excellent, diagnostic assay (κ=0.61).Conclusion:The prognostic role of HR HPV infection in oropharyngeal oncology, with its potential clinical applications, underscores the need for a consensus on the most appropriate detection methods. The present results suggest that viral mRNA detection could be the standard for fresh samples, whereas DNA detection could be routinely used in formalin-fixed, paraffin-embedded samples.British Journal of Cancer advance online publication, 12 February 2013; doi:10.1038/bjc.2013.55 www.bjcancer.com.
British Journal of Cancer 02/2013; · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the prognostic value of "early" and "late" Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET-CT) in patients with head and neck squamous cell carcinoma (HNSCC) treated with radio-chemotherapy (RTCT).
Twenty-six patients treated with RTCT for HNSCC were included. All patients underwent (18)F-FDG PET-CT at baseline ("staging" PET-CT), after 2 weeks of treatment ("early" PET-CT) and 8-12 weeks after treatment ("late" PET-CT). Changes in FDG uptake in the primary tumor (T) and lymph nodes (N) were correlated with local and regional control, respectively; overall metabolic response was correlated with relapse free survival (RFS) and disease specific survival (DSS).
After a median follow-up of 29.2 months, 19/26 patients were living and 17/19 had no evidence of disease. When comparing "staging", "early" and "late" PET results, a significant decrease of FDG SUV(max) in T and N was documented. When correlating changes in FDG uptake in T and N with local and regional control, a statistically significant correlation only with the "late" reduction was found. Statistical analysis failed to demonstrate any correlation between the "early" metabolic response and the patient clinical outcome while the "late" metabolic response revealed a strong correlation with RFS (p = 0.01) and DSS (p = 0.009).
In patients with HNSCC, PET-CT performed after RTCT predicts the clinical outcome, since it strongly correlates with RFS and DSS. On the other hand, the predictive role of "early" metabolic response was not confirmed by this study.
Radiotherapy and Oncology 03/2012; 103(1):63-8. · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES/HYPOTHESIS: The prognosis for laryngeal squamous cell carcinoma (LSCC) has not shown any improvement in the last 30 years because of inadequate prognostic stratification. Therefore, the detection of reliable molecular markers may have a significant impact on clinical practice. As promising data regarding HER1/EGFR have been published, the purpose of the present study was to elucidate the role of the other receptors of the HER family. STUDY DESIGN: Retrospective. METHODS.: We used quantitative immunohistochemistry to evaluate the expression pattern of the HER4 receptors cytokeratin (CK)-14, CK-17, and proliferating cell nuclear antigen in 67 LSCCs and assessed correlations with various prognostic parameters. RESULTS.: HER1 levels inversely correlated with those of HER2-4. The negative prognostic value of HER1 was confirmed, and a protective role for HER2-4 was found. Specifically, the overexpression of HER4 and its nuclear localization are protective and are associated with a better prognosis. CONCLUSIONS.: Semiquantitative evaluation of HER2-4 provides predictive information that can be combined with HER1 expression data for molecular characterization of LSCC. The pattern of localization of HER4 is an easily evaluable qualitative parameter with a clear correlation with prognosis. The immunohistochemical methods described in this article are reliable, reproducible, and potentially translatable to clinical practice.
The Laryngoscope 03/2012; 122(8):1724-33. · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Treatment for laryngeal squamous cell carcinoma (SCC) has been predominantly surgical for decades, but in the last 20 years nonsurgical modalities (radiotherapy), with the aim of organ preservation, also became predominant among advanced stages. Retrospectively evaluating our series of stage III and stage IV laryngeal SCCs, we compared the 2 main therapeutic modalities.
Medical records of 65 consecutive patients with advanced laryngeal SCC, from November 2005 to January 2009, were reviewed.
Among irradiated patients 2-year organ preservation was 86% for cT2, 43% for cT3, and 17% for cT4a (p = .037, Wilcoxon test). With respect to survival, the only significant differences between surgery and radiotherapy were detected among cT4a SCCs (p = .03, Wilcoxon test), in favor of surgery.
The present results confirm the surgical recommendation for cT4a laryngeal SCCs. On the other hand, for T < 4, our results confirm that radiochemotherapy warrants a survival similar to that of total laryngectomy, thus allowing us to preserve the larynx in a relevant number of cases.
Head & Neck 06/2011; 34(4):573-9. · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Parotid gland tumours account for 80% of all salivary gland neoplasms, 20% of these are malignant, but in daily clinical practice most parotid masses are operated on before obtaining the final histological diagnosis. This clinical setting further complicates the critical point of parotid surgery, which is the management of the facial nerve. In the present study, data were evaluated referring to 540 patients who underwent parotidectomy for a mass which was discovered to be a benign (470 cases) or a malignant (70 cases) neoplasm, between November 1994 and December 2007, at our Institution. The most significant single parameter in this series of malignancies regarding disease specific survival was the clinical involvement of the facial nerve at diagnosis (p = 0.006). Also for this reason, as there is no evidence that liberal VIIth nerve sacrifice improves prognosis, when it is not clinically involved, every attempt is made to dissect and preserve it. At present, the most complicated situation concerning nerve preservation may be, on the other hand, recurrence of a benign tumour, in particular pleomorphic adenoma, which, in our series, has a higher incidence (8.3%) of permanent facial dysfunction, than surgery with nerve preservation for malignancy (3.7%).
Acta otorhinolaryngologica Italica: organo ufficiale della Società italiana di otorinolaringologia e chirurgia cervico-facciale 06/2011; 31(3):135-43. · 0.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Microvascular free tissue transfer in head and neck reconstruction requires suitable recipient vessels which are frequently compromised by prior surgery or radiotherapy to the neck. This article details a new technique of arterial free flap pedicle anastomosis to the internal carotid artery in a vessel-depleted neck. A 63-year-old female was referred because of recurrence of squamous cell carcinoma of the tongue, which involved the left-sided tongue base and pharynx with circumferential involvement of the homolateral external carotid artery. This artery and its branches were excluded as potential recipients. To close the defect after tumor excision, a free vertical rectus abdominis muscle arterial flap pedicle was anastomosed to the homolateral internal carotid artery with the help of a Pruitt-Inahara outlying carotid shunt. The venous anastomosis was performed to the internal jugular vein. The VRAM flap survived without complications. This procedure is to be considered an alternative rescue technique for salvage reconstruction in vessel depleted necks.
[Show abstract][Hide abstract] ABSTRACT: It is estimated that about 92,000 new cases of oral cavity and pharyngeal cancer occurred in Europe in 2008. During the past 30 years in the USA and Western Europe, the prognosis for oral cancer has clearly improved thanks to the possibility of reconstruction with microvascular free flaps, resulting in broader and safer resections. The anterolateral thigh flap is now being increasingly employed for this goal. The aim of the present work is to evaluate the anterolateral thigh free flap in the reconstruction of oral cavity defects.
Between July 2004 and February 2009, we harvested 73 free flaps for the reconstruction of soft tissue defects in the oral cavity of 70 patients at our institution. The oncological and functional results in these 70 patients were evaluated, particularly in those patients reconstructed with anterolateral thigh (ALT) free flap. We also evaluated the quality of life using the FACT-H&N questionnaire.
We observed no significant differences in functional and oncological results between patients reconstructed by ALT and patients reconstructed with other flaps. Swallowing may be more difficult in patients who undergo adjuvant irradiation.
In our opinion, the very low morbidity at the donor site, great versatility, and very long pedicle make the ALT free flap the first choice for reconstructing soft tissue defects in the oral cavity (particularly mobile tongue).
[Show abstract][Hide abstract] ABSTRACT: To compare oncological outcome and voice quality among a uniform and well-defined subset of patients with T1 glottic carcinoma.
Patients, affected by laryngeal glottic carcinoma, treated by laser CO2 surgery or radiotherapy, have been analyzed. Overall survival and disease-free survival were calculated. In order to verify differences in functional outcomes and voice quality, all patients were interviewed during their last follow-up visit during 2009 using the VHI (Voice Handicap Index) questionnaire. The data were analyzed using the MedCalc software.
A total of 143 patients were analyzed: 73 underwent surgery and 70 underwent radiotherapy. No statistically significant differences were found between the two groups in terms of overall survival and disease-free survival; dividing patients into stages T1a and T1b also made no difference. In order to evaluate the differences in outcomes for surgery and radiotherapy, patients were interviewed using the VHI questionnaire. Better scores for each category in the VHI were found for patients receiving radiotherapy compared to surgery (physical: p = 0.0023; functional: p < 0.0001; environmental: p < 0.001). The median VHI score for radiotherapy patients was 4, while for surgical patients it was 18 (p < 0.0001).
This study confirms the well-known knowledge that results from radiotherapy and surgery in early glottic cancer treatment are equivalent. Furthermore, the role of patient preference in the treatment modality choice and the value of a multidisciplinary approach for a detailed and multi-oriented discussion with the patient are outlined.
Strahlentherapie und Onkologie 11/2010; 186(11):607-13. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The full clinical relevance of the expression pattern of HER family of type I receptor tyrosine kinases in laryngeal squamous cell carcinoma remains to be elucidated. We evaluated the clinical relevance of such parameter in our population.
This study examined the expression pattern of HER family receptor members by quantitative immunohistochemistry and the amount of the EGF binding sites by a radioligand binding assay, in the same group of 67 LSCC patients, analysing the correlation between the expression of the four HER receptors and the clinical and prognostic parameters.
HER1 levels inversely correlated with that of HER2-4, while HER2-4 directly correlated among them. Cox univariate analysis using HER1-4 values as continuous covariates indicated that HER1 expression was directly associated with the risk of death and relapse while that of HER2-4 was inversely associated with the risk of death. Among the patients with high HER1 expressing tumours, those with tumours co-expressing HER2-4 showed a lower risk of death and relapse (in particular regional relapse) than those with tumours displaying a negative HER2-4 status.
The evaluation of HER2-4 status adds more power to the prognostic role of HER1 detection. In the era of molecularly targeted therapy, the expression of HER family of receptor tyrosine kinases in LSCC may hold relevant clinical significance and turn out to be a key factor in prognostic assessment and in treatment planning.
European journal of cancer (Oxford, England: 1990) 02/2010; 46(6):1144-52. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pharyngocutaneous fistula is the most common non-fatal complication following total laryngectomy. To start oral feeding and exclude the presence of a pharyngocutaneous fistula, a subjective test and instrumental assessments using videofluoroscopy, have been described. The aim of this study was to evaluate the effectiveness of oral-pharyngo-oesophageal scintigraphy as an objective and non-invasive tool to establish presence, site and dimensions of the fistula. Observations were performed on 3 male patients, mean age 65 years, who underwent total laryngectomy and mono or bilateral neck dissection after failure of radiotherapy in 2 cases and of conservative laryngeal surgery in the third case, complicated by post-operative pharyngocutaneous fistula. Oral-pharyngo-oesophageal scintigraphy dynamic study with sequential images were obtained during the swallowing phases. In case 1, the test showed a wide pharyngocutaneous fistula the internal orifice of which was at the level of the base of the tongue: on the scintigraphic images, the radiomarked water bolus, from the fistulous orifice, descended along the stoma walls and only a small part reached the oesophagus. In the other two patients, the pharyngocutaneous fistula was small and the internal fistulous orifice was detected in the lower part of T-suture line. In conclusion, scintigraphy offered the possibility to precisely identify presence of pharyngocutaneous fistula and location of its internal orifice and to monitor its spontaneous closure. Therefore, important information could be obtained regarding the suture line status and the possibility of deciding whether to remove the nasogastric tube or to leave it in place. Finally, these data showed that oral-pharyngo-oesophageal scintigraphy could be performed in the early post-operative period to optimize starting safe oral feeding.
Acta otorhinolaryngologica Italica: organo ufficiale della Società italiana di otorinolaringologia e chirurgia cervico-facciale 10/2009; 29(5):242-4. · 0.79 Impact Factor