Introduction

Laryngeal papillomatosis (LP) is a disease characterized by proliferation of benign epithelial lesions of verricous aspect that can be sessile or pediculated, single or multiple and it is frequently confluent, leading to upper airway obstruction. Etiology is viral, by human papillomavirus (HPV), especially types HPV-6 and HPV-11. According to the literature, in the larynx, the sites normally affected are the vocal folds, the epiglottis and the vestibular folds. Even though it affects primarily the larynx, the disease can also affect the mouth, nose, pharynx, esophagus and the whole tracheobronchial tree 1, 2, 3.

It is a benign disease that normally has very aggressive evolution and had caused frustration to Otorhinolaryngologists for centuries. Surgical treatment, with removal of the lesion, has proved to be not very effective. Many times, recurrences occur within 2 weeks, which requires repetitive manipulations of the larynx and can lead to permanent sequelae such as stenosis, anterior and posterior webs, vocal fold damage, formation of laryngeal granuloma, among others 4, 5, 6.

A number of therapeutic alternatives has been studied to control the disease, such as the use of interferon, anti-metabolic, podofilin, hormone, photodynamic therapy, indol-e-carbinol and antiviral drugs. The antiviral drugs used to treat laryngeal papillomatosis include Ribavirin, Acyclovir and more recently, Cidofovir. Among them, Cidofovir has had the most promising results 7, 8, 9, 10, 11. However, upon reviewing the literature, it is noticed that there is an absence of standardization in the classification and staging the papillomatous lesions. At the same time, there is great variation concerning the sites and degree of affection. In 1998, Derkay(12) suggested a staging system in which he proposed the division of the larynx in epiglottis (lingual surface, laryngeal surface), right and left aryepiglottic folds, right and left vestibular folds, right and left vocal folds, right and left arytenoids, anterior and posterior commissure and subglottis, and created scores 0-3, being that 0 was absence of lesion, 1 was minimum lesion, 2 was moderate lesion and 3 was severe lesion. They added up the affected site to quantify the intensity of the disease and the response to therapy. Later, Pransky et al (9,10) , based on this staging, demonstrated the results with the use of Cidofovir in recurrent laryngeal papillomatosis in children.

However, the lack of international or national consensus for local staging and intensity of lesions of papillomatosis hinders the demonstration and comparison of results in treatments proposed for the disease.

Objective

The purpose of the present study was to create a staging classification based on site and degree of laryngeal lesions that is comprehensive and yet easy to understand and apply in the clinical practice of the Otorhinolaryngologist.






Material and Method

The classification proposed here divides the larynx in three levels: supraglottis (S), glottis (G) and infraglottis (I), and in four different grades concerning extension of the lesions. Starting from a focal lesion (grade 1) to an obstructive lesion (grade 4), being that grade 0 represents absence of lesions. The glottis was divided into a and b: if the lesions were limited to one vocal fold it was considered "a" and if affecting both folds, it was considered "b".

S (Supraglottis)
 S1 (focal lesion affecting less than 1/3 of the lumen)
 S2 (one or more foci of lesion affecting less than 2/3 of the lumen)
 S3 (lesion affecting more than 2/3 of the lumen)
 S4 (obstructive lesion or tracheotomy)

G (Glottis)
 G1 (focal lesion in the vocal fold or anterior or posterior commissure, affecting less than 1/3 of vocal fold extension), G1a (in one vocal fold) G1b (in both vocal folds).
 G2 (one or more foci of lesion affecting less than 2/3 of vocal fold extension), G2a (in 1 vocal fold) G2b (in both vocal folds).
 G3 (lesion affecting more than 2/3 of vocal fold extension), G3a (1 vocal fold) G3b (both vocal
 G4 (obstructive lesion or tracheotomy).

I (Infraglottis)
 I1 (focal lesion affecting less than 1/3 of the lumen).
 I2 (one or more lesion foci affecting less than 2/3 of the lumen).
 I3 (lesion affecting more than 2/3 of the lumen).
 I4 (obstructive lesion or tracheotomy).

After the classification based on topography of the larynx, we grouped the four different stages in which:

- Stage I - 1 or 2 levels grade 1
- Stage II - 3 levels grade 1, 1 or 2 levels grade 2, or 1 level grade 3 with the others grade 0 or 1.

- Stage III - 3 levels grade 2, or 1 level grade 3 and the others grades 2 or 3.

- Stage IV - any level grade 4.

Find below some examples:
We studied 74 laryngoscopies including photographic recording of 10 adult patients of Instituto da Laringe (INLAR) who had recurrent laryngeal papillomatosis before and after treatment with cidofovir, to check applicability of staging system and to demonstrate the results with the use of cidofovir in the 10 patients. We considered the staging of the lesion in the first assessment, after usual treatment without Cidofovir and finally, after the use of the medication.

Results

All the 74 tests were analyzed based on the classification and staging systems proposed here.





Discussion

Clinical Otorhinolaryngology still requires standardization in the classification of laryngeal papillomatosis so that we can refer to the lesions or even to new proposed treatments to control the disease using a common language. The only classification that has been proposed was developed based on the idea of TNM staging for malignant tumors, and it was used in all studied patients. Owing to the great diversity of disease manifestation, we consider that staging for laryngeal papillomatous lesions should be comprehensive and easy to apply.

In order to demonstrate the applicability of the classification, we used a population of 10 patients with laryngeal papillomatosis in our institution and classified all the recurrences after regular therapy use, after removing the lesions and applying local cidofovir injections, in order to exemplify the cases and not to demonstrate conclusive results about the new therapeutic method (Table 1). Most studied patients were in stages I and II and lesions in stages III and IV were rare (Table 2).

All patients were adults and did not present extralaryngeal affections. Our purpose with the classification was to show the whole laryngeal extension of the lesions and not to address extralaryngeal affection because we know the disease can affect different pharyngeal sites, oral cavity, nasal cavity, esophagus and tracheobronchial tree. Our staging allowed the demonstration at the supraglottis, glottis and infraglottis levels, sites and lesion grade.

Graph 2 represents the stages of the lesion in the 10 studied patients in three different situations: at initial presentation before therapy, at the last recurrence after conventional treatment and before use of cidofovir, and after the use of the medication at the end of the study. Out of 10 studied patients, 7 did not present recurrence of the lesions at the last situation, that is, after use of cidofovir. This graph allows us to demonstrate the use of the staging system to depict results about the type of therapy (cidofovir) in the treatment of laryngeal papillomatosis.

Conclusion

We concluded that staging of laryngeal papillomatosis lesions based on topographic classification as proposed here proved to be feasible in the studied population.

References

1. Cummings CH, Fredrickson JM et al. Otolaryngology Head & Neck Surgery. Third Edition Copyright © 1998 by Mosby. Vol.3, Cap.99, p. 1901-2.
2. François M. Encyclopedie Médico-Chirurgicale (Editions Scientifiques et Médicales Esevier SAS, Paris 2000) Oto-rhino-laryngologie, 20-705-A-10, 8p.
3. Kashima HK, Leventhal B et al. Sites of Predilection in Recorrent Respiratory Papillomatosis. Ann Otol Rhinol Laryngol 1993;102: 580-3.
4. Doyle DJ, Henderson LA et al. Changes in Human Papillomavirus Typing of Recorrent Respiratory Papillomatosis Progressing to Malignant Neoplasm. Arch Otolaryngol Head Neck Surg Nov 1994;120:1273-6.
5. Doyle DJ, Gianoli GJ et al. Recurrent Respiratory Papillomatosis: Juvenile versus Adult Forms. Laryngoscope May 1994;104:523-7.
6. Hartley C, Hamilton J; et al. Recurrent Respiratory Papillomatosis - The Manchester Experience, 1974-1992. The Journal of Laryngology and Otology 1994;108:226-9.
7. Kiroglu M, Cetik F et al. Acyclovir in the Treatment of Recurrent Respiratory Papillomatosis: A Preliminary Report. American Journal of Otolaryngology 1994;15:212-4.
8. McGlennen RC, Adams GL et al. Pilot Trial of Ribavirin for the Treatment of Laryngeal Papillomatosis. Head Neck Surg nov/dec 1993;504-13.
9. Pransky SM; et al. Intralesional Cidofovir for Recurrent Respiratory Papillomatosis in Children. Arch Otolaryngol Head Neck Surg; 1999;125:1143-8.
10. Pransky SM, Brewster DF; et al. Clinical Update on 10 Children Treated With Intralesional Cidofovir Injections for Severe Recurrent Respiratory Papillomatosis. Arch Otolaryngol Head Neck Surg 2000;126:1239-43.
11. Snoeck R; et al. Treatment of Severe Laryngeal Papillomatosis with Intralesional Injections of Cidofovir. Journal of Medical Virology 1998;54:219-25.
12. Derkay CS. Recurrent Respiratory Papillomatosis. Laryngoscope January 1998;111:57-69.

---

1Post-graduation under course, Discipline of Otorhinolaryngology and Head and Neck Surgery, UNIFESP-EPM
2Faculty Professor, Discipline of Otorhinolaryngology and Head and Neck Surgery, UNIFESP-EPM, Head of the Division of Laryngology and Voice.
3Head of the Discipline of Pediatric Otorhinolaryngology, UNIFESP-EPM.
Address correspondence to: Rua Otonis 674 Vl. Clementino.
Tel/Fax: 55-11 5539-7723 - e-mail: melissa.avelino@uol.com.br
Article submitted on November 13, 2002. Article accepted on June 05, 2003.