Adult-onset Laryngeal Papilloma Research Articles

Methylation of CpG sites in the upstream regulatory region, physical status and mRNA expression of HPV-6 in adult-onset laryngeal papilloma.

The methylation status of HPV-6 upstream regulatory region (URR) in adult-onset laryngeal papillomatosis (AO-LP) remains unclear. The purpose of this study was to investigate the methylation status of URR and the physical status of HPV-6, as well as the dynamic variations of viral load and mRNA expression in AO-LP. We examined 18 specimens from 11 patients with AO-LP by real-time polymerase chain reaction (PCR), bisulfite-sequencing PCR, and amplification of papilloma oncogene transcripts. HPV-6 was identified in 9 of 11 patients (81.8%), and all the 15 specimens derived from 9 HPV-6-positive cases contained only episomal HPV-6 transcripts with intact E2. Three HPV-6-positive patients developed recurrent lesions, and HPV-6 copy numbers and mRNA expression decreased after surgical treatment. Among the 96 CpG sites (16/case), 67 (69.8%) were unmethylated, while 23 (30.2%) were heterogeneous (≥ 1 methylated CpG clone). High viral loads and episomal status of HPV-6 were frequently observed in AO-LP; thus, persistent E6/E7 mRNA expression of LR-HPV-6 may be associated with AO-LP recurrences. Hypomethylation and scattered patterns of methylated CpGs at the URR of HPV-6 were identified in AO-LP.

Therapy of adult-onset laryngeal papilloma: integrallty submucosal dissection of the tumor by CO2 laser

Objective: To evaluate the feasibility and efficacy of the integrallty submucosal resection of adult-onset laryngeal papilloma by CO2 laser. Methods: A group of 64 cases (36 males and 28 females, multipe lesions 54 cases and single lesion 10 cases, aged 18-75 years, mean age 43.13 years) with adult-onset laryngeal papilloma encountered in the first affliated hospital of Sun Yatsen university from 2009 to 2015 was retrospectively analyzed. All cases were treated with integrallty submucosal dissection of the tumor by CO2 laser, and observed the changes of tumor integral scope, inter-operative, operative processes, postoperative voice quality, postoperative scarring, and the tracheotomy conditions, which were analysed and evaluated. Results: A total of 64 patients were followed up from 1 year to 5 years. Preoperative tumor integral scope of these patients averaged of 7.00. A total of 62 cases kept 0 score of the tumor integral scope for at least one year, which lead to a clinical cure rate of 96.9%. The inter-operative averaged of 25.7 months. The total operative processes of these patients were 87 times (mean time 1.36). Four cases resulted in postoperative scarring. However these was a good result in postoperative voice quality with a mean score 4.25. As to the changes of tumor integral scope, all cases got a declining score (mean score 6.72), which resulted in a remission rate of 100%. Conclusion: The integrallty submucosal dissection of adult-onset 1aryngeal papilloma by CO2 laser was an effective way to reduce the tumor integral scope; lengthen their inter-operative; decrease the operative processes, avoid the occurrence of tracheotomy; and improve the postoperative voice quality. Most of the patients could even be cured ultimately.

Extralaryngeal HPV infections in male patients with adult-onset laryngeal papillomatosis

Adult-onset laryngeal papillomatosis is a frequently relapsing disease affecting especially males. We studied the history and prevalence of extralaryngeal HPV infections in these patients to find out their susceptibility to HPV. Of adult-onset laryngeal papilloma male patients treated at Helsinki University Central Hospital over 25 years, we examined 50 for clinical findings, examined Pap and cytological samples from the oral mucosa and urethra and biopsied HPV-suspect lesions. Fifteen female sexual partners underwent gynecological examinations. The history of HPV-associated diseases was also determined from age- and sex-matched control subjects. Of the patients, 16% (8) had a history of genital warts and of the controls, 12.5% (6 of 48). A history of skin warts was more common in patients. Their prevalence of genital warts was higher (3 of 50, 6%) than in the general population (1%, earlier study). Prevalence of oral HPV DNA was 8% (4 of 50). Patients' sexual habits were unexceptional except for an over-representation of high-frequency orogenital sex initiated at a mean of 9.7 years before diagnosis. However, a lack of orogenital contact did not protect them from severe laryngeal disease. Patients with adult-onset laryngeal papillomatosis seem to be prone to HPV infections. Primary laryngeal HPV infection in adolescence may remain latent, requiring cofactors to develop into the clinical disease.

Expression of the the cyclin-kinase inhibitors p21(WAF1) and p27(Kip1) and the p53 tumor suppressor genes in adult-onset laryngeal papillomas

Different types of human papilloma virus are known to be closely associated with laryngeal papillomas. On the other hand, the proliferation of epithelial cells is associated with various abnormalities in the mechanisms of cellular regulation. In this study, we detected the expressions of p53, p21 and p27 proteins in adult-onset laryngeal papillomas by immunohistochemical techniques. The objective of this study is to evaluate the expression of these factors in adult-onset laryngeal papillomas and to determine whether such expression is correlated with the existence of dysplastic epithelium covering the papillomas. Eighteen patients with adult-onset papillomas who were surgically treated at the Department of Otolaryngology at the University of Istanbul between January 1994 and December 1999 were included in this study. Anti-p21, -p27 and -p53 antibodies were used to perform immunostaining. Positive nuclear staining for p21 was detected in 14 of the 18 (78%) cases, especially in the parabasal layer. Also, in 78% of the cases, weak to strong immunoreactivity was observed for p27. In all cases, negative immunoreactivity was observed for p53 throughout the epithelium except for the basal and parabasal cells. A negative correlation was observed between the existence of dysplastic epithelium and p21 expression (P=0.02). In conclusion, variable p21 and p27 expression was detected by immunohistochemistry in our series of 18 cases of adult-onset laryngeal papillomatosis, and a statistically significant inverse correlation was detected between p21 expression and the existence of dysplastic epithelium covering the papillomas. Further prospective studies are warranted to determine the prognostic values of these variables and to evaluate their role in the pathogenesis of adult-onset laryngeal papillomas.

Poor antibody response against human papillomavirus in adult-onset laryngeal papillomatosis.

To investigate whether adult-onset laryngeal papillomatosis induces serum antibodies to the human papillomavirus (HPV), 60 patients underwent a clinical examination, and HPV DNA from their laryngeal biopsy was assayed by PCR and HPV serology with virus-like particles as the antigen. Patients and controls (n = 53) showed no differences in their HPV 6 and 16 antibodies. Patients more often had HPV 11 antibodies, female patients more often than female controls or male patients. Of the female patients, 5 of 15 had a history of genital condylomas and, at the follow-up visit, 5 of 9 had cervical cytology consistent with genital HPV infection. The fact that HPV antibodies did not correlate with clinical features of the laryngeal disease or with HPV DNA detected in the larynx, suggests that HPV antibodies in female patients were induced by genital rather than laryngeal HPV infection. The high prevalence of abnormal Pap smears indicates that gynaecological examination of female adult-onset laryngeal papilloma patients is warranted.

HLA-DQ alleles and human papillomavirus DNA in adult-onset laryngeal papillomatosis.

Sixty-two patients with histologically confirmed adult-onset laryngeal papilloma were clinically examined; their HLA class II DQA1 and DQB1 alleles and the presence and type of human papillomavirus (HPV) in their laryngeal papilloma biopsies were determined by polymerase chain reaction-based methods. No differences in the DQA1 or DQB1 frequencies appeared between the patients as a group and the reference population. When the patients were divided into groups according to number of laryngeal procedures performed, no HLA association was noticed with any group, nor did the presence of HPV-6 or HPV-11 DNA in the laryngeal specimen correlate with HLA type. A suggestive association was found between the DQB1 *0501 allele and the 16 patients whose laryngeal biopsy was HPV-negative, but because of the small series, additional patients need to be studied. Earlier, the DQB1 *0501 allele was reported to be protective against cervical cancer, another HPV-associated disease.

Prognostic value of clinical findings in histologically verified adult-onset laryngeal papillomas.

A retrospective study of adult-onset laryngeal papilloma was performed to clarify whether any clinical features at the time of diagnosis could predict its course. All patients had a histologically confirmed diagnosis of laryngeal papillomas and were treated at Helsinki University Hospital between 1975 and 1994. Those with adult-onset disease and follow-up exceeding 1 year (n = 74) entered the study. Based on the case records surveyed, results suggested two risk factors for frequent laryngeal procedures: young age at onset of papilloma and a lesion extending to the anterior third to the vocal folds. It was not possible to predict the course of the disease by such clinical findings as symptoms or size or number of primary papilloma lesions. As regards the recurrence of disease, the classic division of adult-onset laryngeal papilloma into solitary and multiple type was not found to be clinically relevant.

The presence of human papillomavirus (HPV) in solitary adult laryngeal papillomas demonstrated by in-situ DNA hybridization with sulphonated probes

Human papilloma virus (HPV) types 6 and 11 have been repeatedly demonstrated in multiple laryngeal papillomas, and there is little doubt that these lesions are caused by HPV. It has been clearly demonstrated in recent reports that the clinical course of solitary adult onset laryngeal papillomas is entirely different from that of multiple papillomas of juvenile as well as of adult onset. We here report the presence of HPV types 6 and 11 in 19 out of 20 solitary papillomas from 16 patients, while HPV types 16 and 18 were totally absent. We conclude that the milder clinical course in such patients is most likely to be due to host factors, rather than to viral factors.

Viral etiology of juvenile- and adult-onset squamous papilloma of the larynx.

Juvenile- and adult-onset laryngeal papillomas were examined for the presence of a human papillomavirus (HPV) genome and capsid antigens. DNA was isolated from a portion of tissue removed for therapeutic purposes, and the presence of a papillomavirus genome was detected by Southern transfer analysis. The viral DNA found in the 12 juvenile-onset and the 8 adult-onset laryngeal papillomas examined was identified as HPV-6 on the basis of size, restriction endonuclease digestion patterns, and homology detected under stringent conditions. Restriction endonuclease analysis of the viral genomes revealed at least four different subtypes, designated HPV-6c through HPV-6f. The most common subtype, HPV-6c, was detected in over half of the papillomas studied, including both juvenile and adult types. The remaining tissue was fixed and processed for immunocytochemistry. The immunoperoxidase technique was used with an antiserum that reacts with capsid antigen(s) common to all HPV serotypes. HPV antigen was found in two of the juvenile-onset papillomas and two of the adult-onset papillomas. The antigen was localized to the nucleus and was distributed in the superficial layers of the epithelium. HPV capsid antigen had not previously been detected in cases of adult-onset papilloma, and the HPV genome in both juvenile- and adult-onset laryngeal papillomas had not been characterized. Despite the absence of detectable viral antigen in most of the specimens examined, the presence of the HPV genome provides strong evidence for the papillomavirus etiology of these tumors.

Adult onset laryngeal papillomatosis.

The charts of 22 patients with an onset of laryngeal papillomatosis after age 18 were reviewed retrospectively. The typical patient had hoarseness. Airway obstruction did not occur in this series. One half of the patients had one recurrence or less of their papilloma. The remainder of the patients encountered multiple recurrences. The histologic criteria of mitosis and dysplasia reflected recent past activity and correlated poorly with subsequent clinical behavior. Malignancy did not occur in the larynx of any of these adult onset laryngeal papilloma patients followed from 1 to 20 years.