[Show abstract][Hide abstract] ABSTRACT: We aimed to clarify the possible role of human papillomavirus (HPV) infection in the malignant transformation of sinonasal inverted papilloma (IP).
Subjects comprised 32 patients with chronic rhinosinusitis (CRS), 17 with IP, 5 with IP and squamous cell carcinoma (IP + SCC), and 16 with primary sinonasal SCC. HPV presence, viral loads, and physical status were investigated using polymerase chain reaction. Retinoblastoma (pRb), p53, and p16(INK4a) gene products were investigated by immunohistochemistry.
HPV DNA was detected in 6.3 % of cases with CRS, 29.4 % with IP, 40 % with IP + SCC, and 25 % with SCC. IP cases had significantly higher HPV presence than CRS cases (p = 0.04). High-risk HPV-16 was the most frequently encountered subtype (10/13, 76.9 %). HPV-16 viral loads varied from 2.5 to 7953 E6 copies/50 ng genomic DNA. Patients in the SCC and IP + SCC groups had significantly higher viral loads than those in the IP and CRS groups (p < 0.01). All SCC and IP + SCC patients with HPV-16 demonstrated mixed-type integration, whereas 4 of 5 HPV-16 patients in the IP and CRS groups showed episomal type infection (p = 0.04). Positivity to pRb was found in 78.1 % of CRS, 35.3 % of IP, and 68.8 % of SCC cases. The presence of HPV DNA negatively correlated with pRb expression in SCC (p = 0.029) and IP (P = 0.049) groups. Although 62.5 % of SCC cases exhibited p53 positivity, only 5.9 % of IP, and no CRS cases were positive. Regardless of HPV status, p16(INK4a) positivity was frequently detected in IP cases (82.4 %), less in SCC (12.5 %) cases, and was not detected in the CRS group. Neither the IP nor SCC cohorts showed any correlation between HPV presence and the expression of either p53 or p16(INK4a).
HPV infection was more frequent in the IP, IP + SCC, and SCC groups than the CRS group. Higher viral loads and integration observed in the IP + SCC and SCC groups, and an inverse correlation between HPV presence and positive pRb indicated that persistent infection and integration play a part in tumorigenesis and malignant transformation in certain IP cases. However, p16(INK4a) is not a reliable surrogate marker for HPV infection in IP.
Infectious Agents and Cancer 08/2015; 10(1):23. DOI:10.1186/s13027-015-0019-8 · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patient profiles, compliance with palliative radiotherapy and the treatment outcomes were investigated in head and neck cancer patients who received palliative radiotherapy from 2006 to 2012. Clinicians selected patients who received palliative radiotherapy considering the clinical stage and the general body condition. There were no patients with severe acute or late toxicities during treatment and the completion rate of palliative radiotherapy was 79.3%. The palliative irradiation group showed significantly better overall survival rates as compared to the no-treatment group. Paliative irradiation of the primary tumor and lymph node metastases at the dose of over 50 Gy contributed to long-term disease-free survival and improvement of the quality of life (QOL), including reduction of tumorigenic pain and dysphasia. Thus, palliative radiotherapy may be a useful treatment option for patients with advanced head and neck cancer under the careful management.
[Show abstract][Hide abstract] ABSTRACT: Since bone and soft tissue sarcomas arising from the head and neck region are very rare, the standard treatment protocol has yet to be established. In the present study, 13 cases with bone and soft tissue sarcomas treated from 2007 to 2014 were analyzed. The mean period from initial visit to final pathological diagnosis was approximately 3 weeks, and 38.5% of the cases needed several biopsies for an accurate diagnosis. Death occurred early for those cases in which more than 40 days was needed to obtain the histological diagnosis. The 3-year overall survival in 13 cases was 35.2%. As the cause of death was uncontrolled local lesion, the locoregional control was more important than distant metastasis control for the prognosis. Tumor location, TNM stage, and histological grade affected the prognosis of the sarcomas. Radiation therapy including heavy ion and proton beam radiotherapy was not so effective as the primary treatment, as was the case with salvage treatment of sarcomas in the head and neck. Although the primary treatment of sarcomas was surgical treatment with an adequate margin, an efficient treatment protocol should be established to obtain a better prognosis.
[Show abstract][Hide abstract] ABSTRACT: To investigate the prevalence, genotypes, and prognostic values of Epstein-Barr virus (EBV) and human papillomavirus (HPV) infections in Japanese patients with different types of head and neck cancer (HNC).
HPV and EBV DNA, EBV genotypes and LMP-1 variants, and HPV mRNA expression were detected by PCR from fresh-frozen HNC samples. HPV genotypes were determined by direct sequencing, and EBV encoded RNA (EBER) was examined by in situ hybridization.
Of the 209 HNC patients, 63 (30.1%) had HPV infection, and HPV-16 was the most common subtype (86.9%). HPV E6/E7 mRNA expression was found in 23 of 60 (38.3%) HPV DNA-positive cases detected. The site of highest prevalence of HPV was the oropharynx (45.9%). Among 146 (69.9%) HNCs in which EBV DNA was identified, 107 (73.3%) and 27 (18.5%) contained types A and B, respectively, and 124 (84.9%) showed the existence of del-LMP-1. However, only 13 (6.2%) HNCs were positive for EBER, 12 (92.3%) of which derived from the nasopharynx. Co-infection of HPV and EBER was found in only 1.0% of HNCs and 10.0% of NPCs. Kaplan-Meier survival analysis showed significantly better disease-specific and overall survival in the HPV DNA+/mRNA+ oropharyngeal squamous cell carcinoma (OPC) patients than in the other OPC patients (P = 0.027 and 0.017, respectively). Multivariate analysis showed that stage T1-3 (P = 0.002) and HPV mRNA-positive status (P = 0.061) independently predicted better disease-specific survival. No significant difference in disease-specific survival was found between the EBER-positive and -negative NPC patients (P = 0.155).
Our findings indicate that co-infection with HPV and EBV is rare in HNC. Oropharyngeal SCC with active HPV infection was related to a highly favorable outcome, while EBV status was not prognostic in the NPC cohort.
PLoS ONE 11/2014; 9(11):e113702. DOI:10.1371/journal.pone.0113702 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate human papillomavirus (HPV) infection as a predictor of concurrent chemoradiotherapy (CCRT) response and indicator of planned neck dissection (PND) for patients with advanced oropharyngeal squamous cell carcinoma (OPSCC; stage III/IV). Overall, 39 OPSCC patients (32 men, 7 women; median age 61 years, range 39-79 years) were enrolled. The primary lesion and whole neck were irradiated up to 50.4 Gy, and subsequently the primary site and metastatic lymph nodes were boosted with a further 16.2 Gy. Although several chemotherapy regimens were employed, 82.1% of OPSCC patients received the combination of nedaplatin and 5-fluorouracil. HPV-related OPSCC (16 cases) was defined as both HPV DNA-positive status by polymerase chain reaction and p16INK4a overexpression by immunohistochemistry. Patients with N2 and N3 disease received PND 2-3 months after CCRT completion. Compared to non-responders, CCRT responders showed significantly lower nodal stage (N0 to N2b) and HPV-positive status in univariate analysis. Patients with HPV-related OPSCC had longer time to treatment failure (TTF) than those with HPV-unrelated OPSCC (p=0.040). Three-year TTF was 81.3 and 47.8% in the HPV-related and HPV-unrelated groups, respectively. There were also significant differences in disease-free survival (DFS) between the two OPSCC patient groups (p=0.042). Three-year DFS was 93.8 and 66.7% in patients with HPV-related and HPV-unrelated OPSCC, respectively. Multivariate logistic analysis showed a lower risk of TTF event occurrence in HPV-related OPSCC (p=0.041) than in HPV-unrelated OPSCC. Thus, HPV testing in addition to nodal stage was useful for predicting CCRT response, especially in advanced OPSCC. Because patients who received PND showed moderate locoregional control, PND is an effective surgical procedure for controlling neck lesions in patients with advanced HPV-unrelated disease.
International Journal of Oncology 06/2014; 45(3). DOI:10.3892/ijo.2014.2504 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) patients with human papillomavirus (HPV) infection have better prognosis than those without HPV infection. Although p16INK4a expression is used as a surrogate marker for HPV infection, there is controversy as to whether p16INK4a reliably indicates HPV infection. Here, to evaluate the accuracy of p16INK4a expression for determining HPV infection and the prognostic value of HPV infection and p16INK4a expression for HNSCC survival, especially oropharyngeal squamous cell carcinoma (OPSCC) survival, 150 fresh-frozen HNSCC samples were analyzed for HPV DNA, E6/E7 mRNA and p16INK4a expression by polymerase chain reaction and immunohistochemistry. p16INK4a expression was scored from 0 to 4 according to the percentage of p16INK4a-positive cells, with overexpression defined as >40% positive cells. Of the 150 tumor samples tested, 10 tumors were nasopharyngeal, 53 oropharyngeal, 39 hypopharyngeal, 24 laryngeal and 24 were located in the oral cavity. HPV DNA was detected in 47 (31.3%) samples, but only 21 also exhibited HPV mRNA expression. Inter-rater agreement was low between p16INK4a expression and HPV DNA presence and between p16INK4a expression and HPV mRNA expression, but was good between the combination of HPV DNA status and p16INK4a overexpression and HPV mRNA expression. Three-year recurrence-free survival was significantly higher for OPSCC patients who were HPV DNA-positive than for OPSCC patients who were HPV DNA-negative (P=0.008) and for OPSCC patients overexpressing p16INK4a than for without overexpressing p16INK4a (P=0.034). Multivariate analysis revealed that T1-3 stage and the combination of HPV DNA positivity and p16INK4a overexpression predicted significantly better recurrence-free survival. This combination is a more accurate marker for active HPV infection in HNSCC than HPV DNA status or general p16INK4a-positive status alone and offers a useful and reliable method for detecting and determining the prognosis of HPV-related HNSCC.
International Journal of Oncology 05/2014; 45(1). DOI:10.3892/ijo.2014.2440 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study investigated the brain activities during phonation of young patients with adductor spasmodic dysphonia (ADSD) of relatively short disease duration (<10 years).
Six subjects with ADSD of short duration (mean age: 24. 3 years; mean disease duration: 41 months) and six healthy controls (mean age: 30.8 years) underwent functional magnetic resonance imaging (fMRI) using a sparse sampling method to identify brain activity during vowel phonation (/i:/). Intragroup and intergroup analyses were performed using statistical parametric mapping software.
Areas of activation in the ADSD and control groups were similar to those reported previously for vowel phonation. All of the activated areas were observed bilaterally and symmetrically. Intergroup analysis revealed higher brain activities in the SD group in the auditory-related areas (Brodmann's areas [BA] 40, 41), motor speech areas (BA44, 45), bilateral insula (BA13), bilateral cerebellum, and middle frontal gyrus (BA46). Areas with lower activation were in the left primary sensory area (BA1-3) and bilateral subcortical nucleus (putamen and globus pallidus).
The auditory cortical responses observed may reflect that young ADSD patients control their voice by use of the motor speech area, insula, inferior parietal cortex, and cerebellum. Neural activity in the primary sensory area and basal ganglia may affect the voice symptoms of young ADSD patients with short disease duration.
[Show abstract][Hide abstract] ABSTRACT: Background:
The purpose of this study was to determine prospectively both human papillomavirus (HPV) load and physical status in different types of head and neck squamous cell carcinoma (HNSCC).
HPV DNA, E6/E7 mRNA expression, viral load, and physical status of 184 patients with HNSCC were examined simultaneously by polymerase chain reaction (PCR)-based methods.
The HPV genome was detected in 54 HNSCC samples (29.3%), particularly in tonsillar carcinomas (69.6%). Compared with nonoropharyngeal HNSCC, oropharyngeal carcinoma harbored a relatively higher viral load, especially in tonsillar carcinoma. Although integrated or mixed status was observed in 75.6% of HPV-16-positive samples, E6/E7 mRNA transcripts were detected in only 27.5% of HPV DNA-positive cases. High HPV-16 load correlated significantly with E6/E7 mRNA expression.
E6/E7 mRNA expression in patients with HNSCC with low viral load remains low even in cases of integration to the host genome. Tonsillar carcinomas were significantly associated with HPV among various types of HNSCC.
Head & Neck 06/2013; 35(6). DOI:10.1002/hed.23034 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The clinical importance of serum squamous cell carcinoma antigen (SCCA) and SCCA subclasses has not been established for treating inverted papilloma (IP). The aim of this study was to clarify the clinical importance of serum SCCA and its subclasses in IP, compared with maxillary squamous cell carcinoma and inflammatory disease.
Serum SCCA was measured in 22 patients with IP (IP group), 11 with maxillary squamous cell carcinoma (carcinoma group), and 22 with inflammatory disease (inflammatory group). mRNA expression of SCCA subclasses was examined using quantitative real-time polymerase chain reaction.
In the IP group, 81.8% showed elevated serum SCCA, and 90.3% with recurrent IP showed elevated SCCA. The preoperative SCCA value (mean ± SD, 3.99 ± 4.39) in the IP group was significantly higher than in the carcinoma (1.28 ± 0.88; p = 0.012) and inflammatory (0.60 ± 0.31; p < 0.001) groups. mRNA expression of SCCA1 and SCCA2 in the IP group was higher than in the carcinoma and inflammatory groups. The SCCA2/SCCA1 ratio of mRNA expression (0.11 ± 0.06) in the IP group was similar to that (0.11 ± 0.09) in the inflammatory group, although the ratio (0.20 ± 0.12) in the carcinoma group was significantly higher than in the IP and inflammatory groups. The receiver operating characteristic curve analysis for the SCCA2/SCCA1 ratio to detect carcinoma yielded an area under the curve of 0.760 (95% confidence interval, 0.626-0.894).
The serum level of SCCA is effective for detecting IP, including recurrent IP. In contrast, the SCCA2/SCCA1 ratio is useful for detecting squamous cell carcinoma among other sinonasal diseases.
American Journal of Rhinology and Allergy 09/2012; 26(5):365-70. DOI:10.2500/ajra.2012.26.3797 · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To clarify the synergistic influence of human papillomavirus (HPV) status and squamous cell carcinoma antigen (SCCA) mRNA expression on head and neck squamous cell carcinoma (HNSCC) prognosis, HPV DNA presence and SCCA1 and SCCA2 mRNA expression were determined by PCR and quantitative real-time RT-PCR, respectively, in 121 patients with primary HNSCC who were receiving curative treatment. HPV DNA was detected in 28.1% (34/121) of HNSCC cases, and only high-risk types (HPV-16, HPV-33, HPV-35 and HPV-58) were observed. Positive HPV status showed a significantly better prognosis than negative HPV status (P = 0.022). An elevated SCCA2/SCCA1 mRNA ratio was an independent predictor of disease recurrence (P = 0.004). In addition, HPV-negative patients with a high SCCA2/SCCA1 ratio (>0.27) had a significantly lower recurrence-free survival rate than HPV-negative patients with a low SCCA2/SCCA1 ratio (P < 0.011). Our findings revealed that both HPV status and the SCCA2/SCCA1 mRNA ratio are independently associated with prognosis in HNSCC. Patients with both a HPV-negative status and a high SCCA2/SCCA1 ratio might need intensified treatment and rigorous follow up after treatment because of the high risk of recurrence.
Cancer Science 08/2012; 103(12). DOI:10.1111/cas.12009 · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study investigated prospectively the role of human papillomavirus (HPV) in paranasal inverted papilloma (IP).
HPV presence and viral load and physical status of HPV-16 were examined by polymerase chain reaction-based methods using fresh frozen samples obtained from 13 patients with IP (IP group), 11 with squamous cell carcinoma in the maxillary sinus (SCC group) and 39 with chronic inflammatory lesions (inflammatory group).
The presence of the HPV genome was detected in 46.1%, 27.3% and 7.6% of patients in the IP, SCC and inflammatory groups, respectively. The IP group showed significantly higher HPV-positive rates than the inflammatory group. All types of HPV detected were high-risk HPV, especially HPV-16. The relative HPV-16 copy numbers varied from 2.5 to 1524.1 per 50 ng genomic DNA. The viral load was higher in the IP and SCC groups than in the inflammatory group. In the IP group, no significant relationship was found between HPV-16 viral load and clinical characteristics, or between physical status and clinical characteristics. One patient with IP and concomitant squamous cell carcinoma, however, showed high viral load and integration.
HPV infection is involved in the pathogenesis of IP, and high viral load and integration of HPV have an important role in malignant lesion in association with IP.
[Show abstract][Hide abstract] ABSTRACT: Human papillomavirus (HPV) is classified into low-risk (HPV types 6 and11) and high-risk (HPV types 16, 18, and 33) according to their oncogenic potentials. We report on the incidence of HPV infection in 33 patients with laryngeal carcinoma and 3 with laryngeal papilloma. All of these patients (34 male and 2 female; ages ranging from 27 to 81) were treated between 2007 and July 2011. HPV DNA was examined by polymerase chain reaction (PCR) using freshly frozen samples. The viral load and physical status of HPV were subsequently investigated by real-time PCR of HPV type 16 positive samples.HPV-DNA was detected in 15.2% of patients (5 out of 33) with laryngeal cancer (4 with type 16 and one with type 33) and in 100% of patients (3 of 3) with laryngeal papilloma; all with type 6. Although all HPV type 16 positive samples showed integration, their viral load varied among cases. No significant difference was found for age, smoking, tumor stage, response to treatment, and survival rate between HPV-positive and HPV-negative patients with laryngeal cancer.Considering the high integration rates in type 16 positive samples and the presence of samples with high viral load, high-risk HPV may be important for the etiology of laryngeal cancer as well as oropharyngeal cancer.