人乳头状瘤病毒感染与鼻内翻性乳头状瘤的发病及恶变关系的研究

目的:探讨人乳头状瘤病毒(HPV)感染与鼻内翻性乳头状瘤(NIP)的发病及恶变的关系。方法:将57例NIP患者分为不伴恶变组(45例)和伴恶变组(12例),应用PCR技术,检测其HPV6、11、16、18等4个型别的HPV-DNA,同时以30例鼻息肉患者为对照组。结果:57例NIP患者HPV-DNA总阳性率为64.9%(37/57)。不伴恶变组HPV-DNA阳性率为60%(27/45),均为单一的低危型HPV11型感染;伴恶变组HPV-DNA阳性率为83.3%(10/12),以检出HPV16、18型DNA为主,其中5例为双重感染(4例为HPV16、18型,1例为HPV11、16型),4例为单一型HPV16型感染,1例为单一型HPV11型感染。而30例鼻息肉患者均未检出HPV-DNA。结论:HPV在NIP的发病中有重要作用,而高危型HPV16、18型与NIP恶变可能密切相关。     

鼻腔鼻窦内翻性乳头状瘤恶变鳞状细胞癌中HPV的分布及预后分析

目的检测人类乳头状瘤病毒（ human papillomavirus, HPV）在鼻腔鼻窦内翻性乳头状瘤恶变鳞状细胞癌（squamous cell carcinoma arising from sinonasal inverted papilloma,SCC/IP）中的感染分布,分析两者的预后关系。方法回顾性分析1997年1月~2012年1月符合入组条件的SCC/IP患者共55例,利用“三明治”方法检测其标本HPV的感染状态,采用Kaplan Meier生存分析法研究患者总生存率和疾病特异性生存率,采用Log rank检测进行单因素分析,采用Cox模型进行多因素分析,计数资料之间采用卡方检验。结果HPV感染11例,感染比例为20%(11/55),其中HPV 16型5例,HPV 6型3例,HPV 39型、HPV 18/39型和HPV 33/52/54型各1例。5年总生存率为35.6%,HPV阳性组为18.7%,HPV阴性组为38.9%;5年疾病特异性生存率为42.7%,HPV阳性组为18.7%,HPV阴性组为49.2%。HPV阳性组总体生存率和疾病特异性生存率与HPV阴性组比较,差异无统计学意义(P=0.915,P=0.773), Cox模型分析示HPV状态对总体生存率及疾病特异性生存率亦无影响（P=0.553, P=0.976）。结论SCC/IP中HPV感染率为20%,HPV感染状态对SCC/IP的预后没有影响。     

Presence of human papillomavirus type-6-related sequences in inverted nasal papillomas

Summary Twenty DNA samples obtained from seven cases of inverted papillomas, eight cases of nasal polyps and five cases of chronic sinusitis were investigated by Southern blot hybridization for the possible presence of sequences homologous to human papillomavirus (HPV) types 6, 11, 16 and 18. HPV type-6-related DNA was identified in one of the seven inverted papillomas. The restriction endonuclease cleavage patterns showed that this latter DNA is a new subtype of HPV type 6 DNA. In the other six papillomas and in all cases of nasal polyps and chronic sinusitis, no HPV sequence could be demonstrated, even under low stringent conditions (T _m–40°C). These results indicate that HPV infection might be one of the possible causative factors in the pathogenesis of inverted papillomas but is not essential for the induction of the tumor.     

Absence of high-risk human papilloma virus in p16 positive inverted sinonasal papilloma

ObjectivesSinonasal inverted papilloma (SIP) is a relatively rare disease, and its etiology is not understood. It is characterized by locally aggressive growth and a strong tendency to recur despite its benign histology.AimsThe aim of this study was to identify the presence of human papilloma virus (HPV) and its surrogate marker p16 in SIP tissue samples from a regional cohort.Material and methodsSubjects were identified from our regional center cohort of 88 SIP patients treated between 1984–2014. From these subjects, 54 were included in this study. Of these, 53 biopsies were analyzed with PCR, and 54 samples were immunohistochemically stained for p16. DNA was extracted from histopathologically verified SIP. Genotype screening for 13 high risk-, 5 oncogenic and 6 low risk HPV types was performed using the PapilloCheck® HPV-screening test.ResultsHPV analysis was successful for 38 of 53 samples. Of the 38 successfully analyzed samples, only 2 samples were positive for HPV 11. Notably, p16 was present in the epithelia in all samples, and in the papilloma lesions in 37 samples.ConclusionSince only 2 out of 38 SIPs were positive for HPV (type 11), and at the same time p16 was positive in epithelia in all samples and in 37 of 38 papilloma lesions of the samples, it is concluded that p16 cannot be used as a surrogate marker for high-risk HPV-infection in SIP. We are currently planning a prospective, multicenter study in order to increase the study power and in order to be able to better evaluate the clinical implications of HPV-and p16 in SIP.     

Detection of human papillomavirus type 57 in a case of inverted nasal papillomatosis in Japan

Human papillomavirus (HPV) type 57 DNA was detected in recurrent nasal inverted papillomatosis, in a 60-year-old Japanese male, using Southern blot hybridization. HPV types 6, 11, 16 and 18 were not detectable in the papilloma. Previous studies have shown that HPV types 6, 11, 16 and 18 were mainly found in nasal papillomatosis in other laboratories but the actual detection rate of virus was low. We speculate that this low detection rate may be due to the lack of a method for detecting HPV type 57.     

Human papillomavirus and infiltration of CD8- and Foxp3-positive immune cells in sinonasal inverted papillomas

Abstract

Background: Sinonasal inverted papilloma (IP) is a benign tumor with a high risk of local recurrence and a potential to malignify and Human papillomavirus (HPV) has been suggested an etiological factor. p16INK4a (p16) overexpression is considered a surrogate marker for HPV, but whether p16 and HPV correlate to IP is uncertain. Besides, a prognostic role of tumor infiltrating lymphocytes (TILs) are observed in many tumors, however their role in IP is sparsely studied.

Aims/objectives: We hence analyzed IPs for the presence and the prognostic role of HPV and p16 overexpression together with CD8+ and FoxP3+ TILs in a population-based study.

Material and methods: 98 IP patients diagnosed 2001–2010 were identified from the Swedish Cancer Registry and analyzed for HPV by PCR and p16, CD8 and FoxP3 was by immunohistochemistry.

Results: In total, 12.2% of the IPs were HPV-positive (nine HPV-11, two HPV-6 and one HPV-45). Patients with HPV-positive lesions were younger (p?=?.003) and tended to present with more dysplasia. No correlation was observed between TILs and prognosis.

Conclusions and significance: Our data suggests that patients with HPV-positive IPs present with different clinical characteristics, suggesting possibly different disease entities. Moreover, recurrences may occur >5?years, which should be considered in the follow-up.     

Bilateral inverted papilloma of the middle ear with intracranial involvement and malignant transformation: first reported case

Inverted (Schneiderian) papilloma (IP) is a benign but locally aggressive tumor that is typically located in the sinonasal tract. Middle ear involvement and intracranial extension are rare. We present a patient with a history of a completely resected right nasal cavity IP that returned 7 months later with hearing loss, bilateral aural fullness, and right-sided facial weakness. Work-up revealed middle ear IP, and the patient underwent bilateral mastoidectomies. On both sides, the disease caused erosion of the tegmen and was adherent to the underlying dura. There was dehiscence of the carotid canal wall on the left. On the right, the tumor was discovered to have recurred 3 months after initial resection, resulting in complete facial nerve paralysis and trigeminal paresthesias. A right temporal bone resection was undertaken along with neurosurgery. The IP was discovered to have invaded through the dura of the temporal lobe, incase the internal carotid artery, and infiltrate the trigeminal nerve. The facial and vestibulocochlear nerves were sacrificed on the right. Pathology of the right temporal bone revealed malignant transformation to squamous carcinoma. The patient was referred to radiation oncology for postoperative therapy. To our knowledge, this is the first case of bilateral IP of the middle ear with intracranial involvement and malignant transformation. Discussion points include: 1) management of middle ear IP, 2) carotid canal wall dehiscence in erosive middle ear disease, 3) aggressive surgical excision in locally destructive middle ear tumors, and 4) the role of radiation therapy in malignant transformation of IP.     

Desmoglein 3 is overexpressed in inverted papilloma and squamous cell carcinoma of sinonasal cavity

Objectives/Hypothesis:

We sought to investigate the role of desmoglein 3 in pathogenesis of sinonasal inverted papilloma (IP) and its malignant transformation.

Methods:

Fifteen subjects with sinonasal IP and 15 subjects of normal sphenoid sinus mucosa were enrolled. Each specimen was divided into two portions: one for mRNA expression analysis by real‐time polymerase chain reaction, and the other for detection of targeted proteins by immunohistochemistry analysis. In addition, another 10 cases of IP with squamous cell carcinoma (SCC) were added for immunohistochemistry analysis.

Results:

The mRNA expression level of desmoglein 3 was significantly higher in IP tissues than in the normal sinus mucosa (P < .001). In immunohistochemistry study, desmoglein 3 was detected in plasma membrane areas of IP and IP with SCC tissues, but no obvious expression was found in normal sinus mucosa (total score; both P < .001). Positive desmoglein 3 staining was strongly present in nearly all malignant transformation areas of IP with SCC cases (90%), but only in scattered areas of some cases of IP (53%) (total score; P < .001).

Conclusions:

Desmoglein 3 was overexpressed in IP and IP with SCC, and the overexpression was correlated with malignant transformation of IP. It may provide valuable insight into the pathobiology of this disease, and can potentially provide a venue to predict malignant transformation in sinonasal IP. Laryngoscope, 2010     

Treatment outcomes in the management of inverted papilloma: an analysis of 160 cases

OBJECTIVE: The objective of this study is to compare the surgical options for treatment of inverted papilloma to determine the appropriate indications for conservative and aggressive management. STUDY DESIGN AND SETTING: A retrospective review of 160 patients with a diagnosis of inverted papilloma treated by the two senior authors (w.l. and h.f.b.) between 1973 and 2001. RESULTS: The study group consisted of 124 male and 36 female patients with an average age of 56 years. The follow-up period ranged from 10 months to 16 years (mean, 5.2 years). Seventy-eight patients (49%) had undergone prior surgery. Lateral rhinotomy was performed in 112 patients (70%), with a recurrence rate of 18%. Conservative removal was performed in 41 patients (26%), including 30 (19%) endoscopic approaches, with a recurrence rate of 12%. The remaining patients underwent midfacial degloving, osteoplastic approach, or craniofacial resection. The rate of malignant transformation was 7%. CONCLUSION: We present the largest personal series of cases of inverted papilloma to date. Our data suggest that conservative approaches, especially endoscopic removal, can be performed on selected lesions with recurrence rates that are comparable to those of more aggressive techniques. Those inverted papillomas that recur after treatment may represent a subset of lesions with an inherent aggressiveness, for which optimal treatment has yet to be determined.     

Human papillomavirus in larynx

OBJECTIVES: The core of the present clinical and basic research knowledge of laryngeal human papillomavirus (HPV) infection is described. STUDY DESIGN: Review. METHODS: A computer-aided search of MEDLINE database supplemented by hand searches of key journals was conducted. RESULTS: One of the tumor-promoting factors in the larynx is the HPV found both in normal laryngeal epithelium and in laryngeal tumors. The most important manifestation of laryngeal HPV infection is laryngeal papillomatosis, a rare disease caused by HPV types 6 and 11. In laryngeal carcinogenesis, the role of HPV remains uncertain. The means of transmission of HPV are partly unknown, and the course of laryngeal HPV infection is unpredictable and variable. Treatment of laryngeal papillomatosis is based on surgery, especially on CO2 laser and shaver. Alpha-interferon is the drug of choice in patients whose response to surgery is poor. However, neither interferon nor other antiviral drugs are able to eradicate the virus from laryngeal mucosa. Little is known about immunological mechanisms involved in laryngeal HPV infection, but in defense against HPV cellular immunity is considered a more important mechanism than humoral immunity. A good experimental model of HPV infection is lacking in which the entire viral life cycle can take place. Organotypic cell cultures (collagen rafts) are useful, but the rate-limiting step in this method is the difficulties in culturing HPV-positive epithelial cells. CONCLUSIONS: Although laryngeal papillomatosis is clinically well defined, the mechanisms and treatment modalities of laryngeal HPV infection need further investigations.     

High CT attenuation values relative to the brainstem may predict squamous cell carcinoma arising from inverted papilloma

Abstract

Background: A diagnostic indicator for differentiating squamous cell carcinomas (SCCs) from inverted papillomas (IPs) has not been established.

Objectives: This study aimed to evaluate whether CT attenuation values relative to those of the brainstem (relative CT number) could be useful in differentiating IPs from SCCs.

Material and Methods: Consecutive patients who were pathologically diagnosed with IP or SCC between 2007 and 2017 were retrospectively identified. Relative CT numbers were compared between the two patient groups. The factors with predictive power for differentiating IPs from SCCs were identified by univariate and multivariate logistic regression analyses.

Results: Fifty-four sinonasal tumour cases were finally analysed (IP, 25 cases; SCC, 29 cases). Relative CT numbers were significantly higher in SCC than in IP (p?<?.001). The univariate logistic regression analysis showed BMI, relative CT number, and disease duration to have predictive value for differentiating IPs from SCCs. In the multivariate logistic regression analysis, only the relative CT number had predictive value for distinguishing IP from SCC (odds ratio, 1.97), with a relative CT number of ≥1.4 being significantly associated with SCC.

Conclusions: High relative CT numbers could potentially be used to identify SCCs, and their measurement could provide a basis for differentiating IPs from SCCs.     

Expression of epidermal growth factor receptor in the inverted papilloma and squamous cell carcinoma of nasal cavity

The present study was undertaken to compare positive rate of immunostaining (PR) and positive intensity of immunostaining (PI) of epidermal growth factor receptor (EGFR) in inverted papilloma (IP), synchronous carcinoma with IP and metachronous carcinoma with IP of the nasal cavity. Ten subjects with nasal polyps, ten subjects with inverted papilloma (IP), five subjects with synchronous carcinoma with IP and ten subjects with metachronous carcinoma with IP were enrolled with a control group of ten subjects of inferior turbinate. Each specimen was divided into two portions: one for RNA isolation and the other for detection of EGFR protein. Positive rate of immunostaining, positive intensity of immunostaining for EGFR protein and EGFR mRNA were significantly up-regulated in the IP, synchronous carcinoma with IP and metachronous carcinoma with IP when comparing polyp and normal mucosa. A role for EGFR in the malignant transformation from IP to SCC of the nasal cavity is suggested.     

The serum squamous cell carcinoma antigen level in inverted sinonasal papilloma and nasal polyps patients

ObjectiveTo clarify whether the serum squamous cell carcinoma antigen (SCCA) levels of patients with inverted papilloma (IP) are different from patients with nasal polyps (NP) and rhinitis.Materials and methodsSerum SCCA levels were measured in 30 patients with IP and 30 patients with NP at one day before surgery and seven days after surgery and measured in 28 patients with rhinitis.ResultsElevated serum SCCA levels (>1.5 ng/ml) were found in 80.0% of patients in the IP group, 6.7% of patients in the NP group and 14.3% of patients in the rhinitis group, which was a significant difference. The medians of serum SCCA levels in the IP, NP and rhinitis groups were 3.9, 0.8 and 1.1 ng/ml, respectively, which was a significant difference. The SCCA level in IP group was not significantly correlated according to Krouse Staging. There was a significant difference in serum SCCA levels between the pre- and postoperative stages in the IP group, at 3.9 and 0.8 ng/ml, respectively, while in the NP group the levels were 0.8 and 1.0 ng/ml, not significantly different. With regard to the IP diagnosis in the IP and NP group based on the SCCA level (>1.5 ng/ml), sensitivity and specificity was 80.0% and 93.3%, respectively.ConclusionsThe serum SCCA level in patients with IP was elevated and then it decreased after surgery. This was different from NP and rhinitis patients who mostly had normal levels, which did not change.     

New staging system for sinonasal inverted papilloma in the endoscopic era

OBJECTIVES: Advanced endoscopic techniques have emerged as the preferred treatment modality for sinonasal inverted papilloma (IP); however, a staging system that provides prognostic information has not yet been developed. This study aims to develop a clinically relevant staging system for IP managed with the endoscopic approach as the primary surgical modality. DESIGN: A systematic review of the English-language literature (1985-2006) and a single institution's experience. METHODS: From the literature, 445 patients with IP treated by endoscopic resection were identified in 14 reports. Only patients with known IP sites and outcomes were included. RESULTS: Patients were categorized into three groups on the basis of recurrence rates (RR): group A (IP confined to the nasal cavity, ethmoid sinus, and medial maxillary sinus), 3.0% RR (n = 234); group B (IP with lateral maxillary sinus, sphenoid sinus, or frontal sinus involvement), 19.8% RR (n = 177); and group C (IP with extrasinus extension), 35.3% RR (n = 34). Pearson's chi-square test showed statistically significant differences for all pair-wise comparisons between groups (P < .05). Mean follow-up was 39.8 months. CONCLUSIONS: This new staging system for IP provides information about prognosis (as operationally defined by RR) for IP managed by advanced endoscopic techniques. In contrast, other staging systems for IP reflect surgeon's judgment rather than outcomes data. This new classification for IP provides important objective data for preoperative planning and patient counseling.     

鼻腔鼻窦内翻性乳头状瘤人类乳头状瘤病毒DNA检测

为了解鼻腔鼻窦内翻性乳头状瘤与人类乳头状瘤病毒（ＨＰＶ）之间的关系，采用聚合酶链反应，对３８例患者的４４个鼻腔鼻窦内翻性乳头状瘤的病理组织蜡块进行ＨＰＶ－ＤＮＡ的检测。结果显示，３８例中３０例患者的３０个瘤组织蜡块呈ＨＰＶ阳性，总感染率为６８．２％，其中３０例次ＨＰＶ１１型阳性（６８．２％），１８例次ＨＰＶ１６型阳性（４０．９％），２例次ＨＰＶ１８型阳性（４．５％），其中１８例ＨＰＶ１１，１６、２例ＨＰＶ１１，１８呈双重感染。试验表明，ＨＰＶ与鼻腔鼻窦内翻性乳头状瘤在病因上有一定的相关性。     

中耳癌人类乳头状瘤病毒DNA表达的研究

目的 :研究原发性中耳癌人类乳头状瘤病毒 (H PV) DNA的表达情况。方法 :采用多聚酶链反应技术 ,对 5例中耳癌的病理组织蜡块进行 HPV - DNA类型的检测 ,以 8例慢性化脓性中耳炎中耳乳突粘膜为对照组。结果 :5例中耳癌高危型 HPV感染率为 80 % (4 /5 ) ,以 HPV1 6型感染为主 ,而对照组 HPV感染率为 0 % (0 /8) ,经 χ2检验 ,P <0 .0 1。结论 :中耳癌高危型 HPV感染率较高 ,慢性化脓性中耳炎和中耳胆脂瘤以及 HPV感染可能在中耳癌的发生发展中起着重要作用     

High incidence of malignant transformation of laryngeal papilloma in Taiwan

OBJECTIVES: Papillomas of the larynx include solitary laryngeal papilloma and recurrent respiratory papillomatosis. This study investigated the incidence of malignant transformation and assessed possible risk factors for laryngeal papillomas. STUDY DESIGN: A prospective, longitudinal study. METHODS: Twenty-six consecutive laryngeal papilloma patients were prospectively studied for 5 or more years, and each patient was periodically examined at 3 to 6 month intervals. A detailed epidemiologic questionnaire was administered at the initial visit. After enrollment, tissue obtained during each laryngeal surgery was examined by polymerase chain reaction assay for human papilloma virus (HPV) and typing. RESULTS: During 237 person-years of follow-up, six new, pathologically confirmed cases of laryngeal carcinoma were ascertained (incidence 2.5/100 person-years), and all were associated with HPV-6 or HPV-11. Malignant transformation revealed no correlation with the following: age less than 3 years at diagnosis, sex, history of tobacco use, history of alcohol consumption, family history of laryngeal cancer, or type of laryngeal papilloma. Laryngeal papilloma without demonstrable HPV DNA was the only significant risk factor for malignant transformation (P < .05). The cumulative risk of malignant transformation in subjects without demonstrable HPV DNA was significantly higher than that in HPV-positive patients (relative risk, 8.0; 95% confidence interval, 1.1-60.3; P = .05). CONCLUSIONS: A relatively high incidence of malignant transformation of laryngeal papilloma was noted in Taiwanese patients. Patients without demonstrable HPV DNA require more frequent follow-up and may benefit from anti-HPV vaccinations.