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Abstract
Squamous cell papillomas are frequent in the larynx of adults. They also found in children where, because of the much narrower diameter of the airway, the more widespread involvement in the larynx and the greater tendency to recurrence, the symptoms are more serious, and treatment is more urgent and difficult. It is thus customary to divide the condition on the basis of the age of the patient into juvenile and adult types. In some juvenile cases the papillomas persist into adult life. The pathological changes are similar at all ages, and will be described first before a discussion of the natural history of the lesion.
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The technique of in situ hybridization with biotin-labeled probes was applied to 20 patients with laryngeal papillomatosis (9 with adult-onset disease and 11 with juvenile-onset). Ten patients were noted for epithelial transformation of their laryngeal disease. All patients, regardless of their clinical outcome, tested positive for human papillomavirus group 6/11. The biotin method of in situ hybridization proved to be a sensitive method in this study, identifying the infecting viral group in 23 of 24 samples. This study also tested for group 16/18 and is the first to test for the presence of group 31/33/35 in the larynx. These viruses or members of related groups have been reported in malignancies of the head and neck as well as the uterine cervix. They have yet, however, to be identified in benign laryngeal papillomas or laryngeal papillomas that have undergone epithelial transformation.
In a survey of 49 papilloma patients accurate maternal condyloma history was obtained in 31 instances and of these, 21 were positive for the presence of condyloma during pregnancy or parturition. Molecular virological studies indicate that positive hybridization could be demonstrated to human papilloma virus 2 in both laryngeal papilloma and condyloma by the Southern blot technique. Immunoperoxidase staining illustrated the presence of virus-related particles only near the surface of the mucous membrane papilloma, which is in contrast to the definite staining of the stratum granulosum and stratum corneum of verrucae. Collectively this provides convincing evidence for an etiological relationship between condyloma acuminata and some laryngeal papillomata. The highly contagious nature of human papilloma virus infection is discussed and the possibility of cesarian section in the presence of active condyloma must be considered.
Proliferative verrucous leukoplakia and hyperplasia are irreversible clinicopathologic lesions of the oral cavity and upper respiratory tract with considerable potential for evolving into verrucous or other forms of squamous cell carcinoma. Proliferative verrucous leukoplakia is a disease of the oral cavity in which verrucous hyperplasia is a part of its developmental spectrum. Verrucous hyperplasia, at other head and neck mucosal sites, may be associated with papillomas or be a de novo lesion. Human papillomavirus, as a cefaclor, plays a role in some of the lesions. In the instance of verrucous hyperplasia, the authors consider it an early form of verrucous carcinoma and recommend it be treated accordingly.
• Alpha interferon did not prevent the persistence or expression of human papillomavirus (HPV) types 6 or 11 in respiratory tract papillomas. Seventeen patients receiving interferon therapy for a minimum of six months and a maximum of 39 months still had one to ten copies per cell genome of HPV DNA in their laryngeal tissues, seen by Southern blot hybridization. In papillomas that recurred during treatment, HPV RNA could be detected by in situ hybridization, and capsid protein could be detected by immunoperoxidase staining. Persistence of the HPV DNA, and recurrences that occurred during therapy, are attributed to the failure of interferon therapy to eliminate latent virus.
(Arch Otolaryngol Head Neck Surg 1988;114:27-32)
This study attempted to delineate the relationship between juvenile laryngeal papillomatosis (JLP) in children and a history of maternal condyloma at the time of their birth. Over a period of 53 years, from 1930 to 1983, 44 children with the clinical diagnosis of JLP were identified. A maternal history of genital condyloma at the time of their birth was sought. Sixteen had incomplete records. Of the remaining 28, 15 children (54%) had a maternal history of vulvar condyloma at the time of delivery or pregnancy. The association between maternal condyloma and JLP needs to be recognized since the latter causes considerable morbidity and occasional mortality. Additional studies are indicated to establish if cesarean section is necessary in pregnant patients with genital condyloma to prevent JLP in their offspring.
Five antigenically distinct serotypes of human papillomavirus (HPV) cause various cutaneous verrucae with distinct clinical features. Laryngeal and other mucosal papillomas, also suspected to have a viral etiology, were examined for the presence of a genus-specific (common) antigen of HPV using a peroxidase-antiperoxidase (PAP) technique. The primary antiserum used was reactive against laryngeal papillomas from 26 of 35 randomly selected patients (74%); overall, 49 of the 102 squamous papillomas stained were positive for HPV (48%). HPV antigen was not demonstrated within frankly dysplastic squamous cells. Nuclear localization of virus was confirmed by electron microscopy in 3 cases positive for HPV. PAP localization of HPV is rapid and more efficient than routine electron microscopy. Our data indicate a common pathogenesis for some papillomas and cutaneous verrucae and suggest a future role for immunohistochemistry in evaluating the epidemiology and pathobiology of laryngeal papillomatosis.
Sixty-three cases of squamous papillomas of the larynx occurring in adults are presented. Twelve cases started as juvenile papillomas and continued into adult life. Twice as many males as females were in the series. The papillomas were always present on the true vocal cords at presentation, although other parts of the larynx were involved to a variable extent. The symptom of hoarseness gave a good indication as to the state of the larynx during treatment. Malignancy did not develop in patients with papillomas which fulfilled the histological criteria. Papillomas are clusters of thin, cylindrical projections of squamous epithelial covered mucosa with second and even third order branching. Biopsies in 5 cases show papillomatosis of respiratory epithelium, a process which is here described in the larynx for the first time. The prognosis as regards recurrence for 20 patients with solitary lesions was good, for 38 patients with multiple lesions reasonable, but for 5 patients with extensive florid lesions was exceptionally poor.
• A young female patient had juvenile laryngotracheobronchial papillomatosis. Metastasizing squamous cell carcinoma developed in this patient without any prior irradiation. The case is extremely unusual and exhibits multifocal in situ and microinvasive changes in the bronchial papillomas.
(Arch Otolaryngol 1982;108:114-116)
Recurrent respiratory papillomatosis (RRP) has been described to have a juvenile or aggressive form and an adult or less aggressive form. However, the aggressive form may occur in an adult and vice versa. Some authors have reported a quiescence in the juvenile form with the onset of puberty. In order to further characterize these two forms of RRP and to analyze the effects of puberty, we reviewed the records of 32 patients treated for RRP at our institution over a 10-year period. We found that the aggressive form typically occurs in the very youngest of patients (average of 2 years old as compared to an average of 17 years old in the less aggressive form). Although subglottic involvement universally occurred in our group with aggressive disease, approximately 40% developed subglottic disease very early as compared with 20% of patients with less aggressive disease. Additionally, our data do not support the theory of spontaneous regression with the onset of puberty. These and other findings will be discussed in detail. We also propose a new classification for RRP to eliminate confusion.
Eleven adults with laryngeal papillomas were studied for the presence of human papillomavirus (HPV) DNA by in situ hybridization. As well as from the papillomas, three additional biopsies were taken from the normal-appearing mucosa as follows: the involved vocal cord, the opposite vocal cord (when the papilloma was unilateral), and from the ventricular fold on the side of the lesion. These normal tissues were analysed by polymerase chain reaction (PCR) to detect HPV DNA. All except one of the 11 papillomas contained HPV DNA; nine were HPV 6/11 DNA positive and one positive for HPV 16 DNA. The normal-appearing laryngeal mucosa harboured HPV DNA in eight out of 11 patients. The present results strongly support the concept that the adult-type laryngeal papilloma is an HPV-induced lesion, mostly due to HPV types 6 and 11. The persistence of HPV DNA in the adjacent normal epithelium is consistent with the frequent recurrence of these lesions.
Juvenile-onset recurrent respiratory papillomatosis is a vertically transmitted disease caused by members of the human papilloma virus family. Characterized by the relentless growth of papillomatous lesions of the larynx, recurrent respiratory papillomatosis imposes significant morbidity on patients and strain on their families. Surgical excision of the papillomata remains the mainstay of therapy, but human papilloma virus DNA persists in adjacent, normal-appearing mucosa and likely serves as a reservoir for viral reseeding. Despite multiple adjuvant treatment modalities, a cure for recurrent respiratory papillomatosis remains elusive. Most afflicted patients eventually enter spontaneous remission, but some endure several hundred surgical procedures before this welcome respite.
Sections of vocal cord biopsies from 47 cases in whom had been previously assessed by a dysplasia grading system at from I to III, were reclassified according to the Ljubljana system. The majority of the Grade I lesions were reclassified as "non-risky", but a small number were put into the risky or even carcinoma in situ groups. While most of the Grade III cases were reclassified as "risky" there were a few who were assigned to a non-risky category. It is suggested that with the Ljubljana histological grading system a more clear-cut separation of cases with risk of developing vocal cord malignancy from those with no such risk, is possible. Attention is drawn to a lesion denoted as "large cell hyperplasia", which is not covered in the grading or Ljubljana categorization of vocal cord lesions. The malpighian cells in this lesion are enlarged to over 30 microm in diameter, and show prominent nucleoli: apoptotic cells are prominent. Evidence is presented that this may be a categorical risk for the development of malignant changes.
To validate histological criteria for the grading of epithelial hyperplastic laryngeal lesions (EHHL) (dysplastic laryngeal lesions), we used a system that had been devised and tested in Ljubljana, Slovenia over many years and was felt to be more appropriate to laryngeal pathology than is the commonly-used model of intraepithelial neoplasia in the cervix.
Vocal cord biopsies of 45 patients with a broad spectrum of EHLL were reviewed. Detailed histological criteria were formulated for each of the four grades of EHLL in the Ljubljana classification, comprising simple hyperplasia (benign spinous layer augmentation), abnormal hyperplasia (benign basal and parabasal layer augmentation), atypical hyperplasia (risky for malignancy) and carcinoma in situ (actually malignant, but without invasion).
Using these criteria a high degree of concordance of histological diagnoses of grading levels for the Ljubljana classification was achieved between the pathologists of the Working Group. The system was found to be more precise for routine diagnostic work than the others in vogue. The different grades of the Ljubljana classification correspond to significantly different levels yielded in each grade by the semiobjective methods of quantitative morphometry and immunohistochemistry.
Laryngeal papillomatosis; classification and course
- H Lindberg
- S Oster
- I Oxland
Squamous papillomas of the larynx in adults. A review of 63 cases
- Jwr Capper
- Cm Bailey
- L Michaels