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{{Infobox medical condition (new)
{{Infobox medical condition (new)
| name = Laryngeal papillomatosis
| name = Laryngeal papillomatosis
|image=CT tracheal papillomatosis volume.png|caption=Volumetric CT rendering of multiple tracheal papilloma (arrow).
| image = CT tracheal papillomatosis volume.png
| caption = Volumetric CT rendering of multiple tracheal papilloma (arrow)
|synonyms= Adult papillomatosis, Juvenile papillomatosis, Recurrent respiratory papillomatosis, Squamous cell papillomatosis, Nonkeratinized papillomatosis
| synonyms = Adult papillomatosis, Juvenile papillomatosis, Recurrent respiratory papillomatosis (RRP), Squamous cell papillomatosis, Nonkeratinized papillomatosis|
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| complications =Squamous cell carcinoma
| complications = Squamous cell carcinoma
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| causes =HPV infection
| risks =
| causes = HPV infection
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'''Laryngeal papillomatosis''', also known as '''recurrent respiratory papillomatosis''' or '''glottal papillomatosis''', is a [[Rare disease|rare medical condition]] in which benign [[Neoplasm|tumors]] ([[papilloma]]) form along the [[aerodigestive tract]].<ref name="IARC" /><ref name="Carifi2015" /> There are two variants based on the age of onset: juvenile and adult laryngeal papillomatosis.<ref name="Taliercio2015" /> The tumors are caused by [[human papillomavirus]] (HPV) infection of the throat. The tumors may lead to narrowing of the [[airway]], which may cause vocal changes or airway obstruction.<ref name="MehtaBook2016">{{Cite book|title=Diseases of the central airways : a clinical guide|publisher=Springer|others=Mehta, Atul C.,, Jain, Prasoon,, Gildea, Thomas R.|year=2016|isbn=9783319298283|location=|pages=215–218|oclc=945577007}}</ref><ref name="Venkatesan2012" /> Laryngeal papillomatosis is initially diagnosed through [[indirect laryngoscopy]] upon observation of growths on the larynx and can be confirmed through a [[biopsy]].<ref name="GrimesBook2014" /><ref name="Fortes2017" /><ref name="NIDCD">{{Cite web|url=https://www.nidcd.nih.gov/health/recurrent-respiratory-papillomatosis|title=Recurrent Respiratory Papillomatosis or Laryngeal Papillomatosis|date=2015-08-18|work=NIDCD|language=en|access-date=2017-10-21}}</ref> Treatment for laryngeal papillomatosis aims to remove the papillomas and limit their recurrence.<ref name="Alfano2014" /> Due to the recurrent nature of the virus, repeated treatments usually are needed.<ref name="Fortes2017" /><ref name="Alfano2014" /><ref name="Carifi2015" /><ref name="Avelino2013" /> Laryngeal papillomatosis is primarily treated surgically, though supplemental nonsurgical and/or medical treatments may be considered in some cases.<ref name="Fortes2017" /><ref name="Avelino2013" /> The evolution of laryngeal papillomatosis is highly variable.<ref name="MehtaBook2016" /><ref name="IARC" /> Though total recovery may be observed, it is often persistent despite treatment.<ref name=":0" /><ref name="NIDCD" /><ref name="IARC" /> The number of new cases of laryngeal papillomatosis cases is at approximately 4.3 cases per 100,000 children and 1.8 cases per 100,000 adults annually.<ref name="IARC" /><ref name="GrimesBook2014" /><ref name="Fortes2017" /><ref name="ColtonBook2011" />
'''Laryngeal papillomatosis''', also known as '''recurrent respiratory papillomatosis''' ('''RRP''') or '''glottal papillomatosis''', is a [[Rare disease|rare medical condition]] in which benign [[Neoplasm|tumors]] ([[papilloma]]) form along the [[aerodigestive tract]].<ref name="IARC" /><ref name="Carifi2015" /> There are two variants based on the age of onset: juvenile and adult laryngeal papillomatosis.<ref name="Taliercio2015" /> The tumors are caused by [[human papillomavirus]] (HPV) infection of the throat. The tumors may lead to narrowing of the [[airway]], which may cause vocal changes or airway obstruction.<ref name="MehtaBook2016">{{Cite book|title=Diseases of the central airways : a clinical guide|publisher=Springer| vauthors = Mehta AC, Jain P, Prasoon G, Gildea TR |year=2016|isbn=9783319298283|pages=215–218|oclc=945577007}}</ref><ref name="Venkatesan2012" /> Laryngeal papillomatosis is initially diagnosed through [[indirect laryngoscopy]] upon observation of growths on the larynx and can be confirmed through a [[biopsy]].<ref name="GrimesBook2014" /><ref name="Fortes2017" /><ref name="NIDCD">{{Cite web|url=https://www.nidcd.nih.gov/health/recurrent-respiratory-papillomatosis|title=Recurrent Respiratory Papillomatosis or Laryngeal Papillomatosis|date=2015-08-18|work=NIDCD|language=en|access-date=2017-10-21}}</ref> Treatment for laryngeal papillomatosis aims to remove the papillomas and limit their recurrence.<ref name="Alfano2014" /> Due to the recurrent nature of the virus, repeated treatments usually are needed.<ref name="Fortes2017" /><ref name="Alfano2014" /><ref name="Carifi2015" /><ref name="Avelino2013" /> Laryngeal papillomatosis is primarily treated surgically, though supplemental nonsurgical and/or medical treatments may be considered in some cases.<ref name="Fortes2017" /><ref name="Avelino2013" /> The evolution of laryngeal papillomatosis is highly variable.<ref name="MehtaBook2016" /><ref name="IARC" /> Though total recovery may be observed, it is often persistent despite treatment.<ref name=":0" /><ref name="NIDCD" /><ref name="IARC" /> The number of new cases of laryngeal papillomatosis cases is approximately 4.3 cases per 100,000 children and 1.8 cases per 100,000 adults annually.<ref name="IARC" /><ref name="GrimesBook2014" /><ref name="Fortes2017" /><ref name="ColtonBook2011" />


<nowiki/>__TOC__
__TOC__


== Signs and symptoms ==
== Signs and symptoms ==
A common symptom of laryngeal papillomatosis is a perceptual change in voice quality. More specifically, [[Hoarse voice|hoarseness]] is observed.<ref name="MehtaBook2016" /><ref name=Venkatesan2012>{{Cite journal|last1=Venkatesan|first1=Naren N.|last2=Pine|first2=Harold S.|last3=Underbrink|first3=Michael P.|date=June 2012|title=Recurrent respiratory papillomatosis|journal=Otolaryngologic Clinics of North America|volume=45|issue=3|pages=671–694, viii–ix|doi=10.1016/j.otc.2012.03.006|issn=1557-8259|pmc=3682415|pmid=22588043}}</ref> As a consequence of the narrowing of the [[Larynx|laryngeal]] or [[trachea]]l parts of the airway, [[shortness of breath]], chronic cough and [[stridor]] (i.e. noisy breathing which can sound like a whistle or a snore), can be present.<ref name="MehtaBook2016" /><ref name=Venkatesan2012/> As the disease progresses, occurrence of secondary symptoms such as [[dysphagia]], [[pneumonia]], [[acute respiratory distress syndrome]], failure to thrive, and recurrent upper respiratory infections can be diagnosed.<ref name="MehtaBook2016" /><ref name=Venkatesan2012/> The risk of laryngeal papillomatosis spreading to the lungs is higher in the juvenile-onset than the adult-onset.<ref name="Taliercio2015" /> In children, symptoms are usually more severe and often mistaken for manifestations of other diseases such as [[asthma]], [[croup]] or [[bronchitis]]. Therefore, diagnosis is usually delayed.<ref name=NIDCD/><ref name=Venkatesan2012/>
A common symptom of laryngeal papillomatosis is a change in voice quality. More specifically, [[Hoarse voice|hoarseness]] is observed.<ref name="MehtaBook2016" /><ref name=Venkatesan2012>{{cite journal | vauthors = Venkatesan NN, Pine HS, Underbrink MP | title = Recurrent respiratory papillomatosis | journal = Otolaryngologic Clinics of North America | volume = 45 | issue = 3 | pages = 671–694, viii–ix | date = June 2012 | pmid = 22588043 | pmc = 3682415 | doi = 10.1016/j.otc.2012.03.006 }}</ref> As a consequence of the narrowing of the [[Larynx|laryngeal]] or [[trachea]]l parts of the airway, [[shortness of breath]], chronic cough and [[stridor]] (i.e. noisy breathing which can sound like a whistle or a snore), can be present.<ref name="MehtaBook2016" /><ref name=Venkatesan2012/> As the disease progresses, occurrence of secondary symptoms such as [[dysphagia]], [[pneumonia]], [[acute respiratory distress syndrome]], failure to thrive, and recurrent upper respiratory infections can be diagnosed.<ref name="MehtaBook2016" /><ref name=Venkatesan2012/> The risk of laryngeal papillomatosis spreading to the lungs is higher in the juvenile-onset than the adult-onset.<ref name="Taliercio2015" /> In children, symptoms are usually more severe and often mistaken for manifestations of other diseases such as [[asthma]], [[croup]] or [[bronchitis]]. Therefore, diagnosis is usually delayed.<ref name=NIDCD/><ref name=Venkatesan2012/>


==Cause==
==Cause==
Laryngeal papillomatosis is caused by [[Human papillomavirus infection|human papillomavirus]] (HPV) infection, most frequently genotypes 6 and 11<ref name=Larson2010/> although genotypes 16, 18, 31, and 33 have also been implicated.<ref name="Fortes2017" /> HPV-11 is associated with more aggressive forms of papillomatosis, which may involve more distal parts of the tracheobronchial tree.<ref name="Fortes2017" /> The mode of viral inoculation is hypothesized to vary according to age of disease onset.<ref name="Larson2010" /><ref name="BarnesBook2005" /> The presence of HPV in the respiratory tract does not necessarily result in the development of laryngeal papillomatosis. Other factors that could be involved include immunodeficiency or other similar infections. For example, laryngeal papillomatosis may become more aggressive due to the presence of certain viruses (e.g., herpes simplex virus, Epstein-Barr virus).<ref name="Carifi2015" />
Laryngeal papillomatosis is caused by [[Human papillomavirus infection|human papillomavirus]] (HPV) infection, most frequently types 6 and 11,<ref name=Larson2010/> although genotypes 16, 18, 31, and 33 have also been implicated.<ref name="Fortes2017" /> HPV-11 is associated with more aggressive forms of papillomatosis, which may involve more distal parts of the tracheobronchial tree.<ref name="Fortes2017" /> The mode of viral inoculation is hypothesized to vary according to age of disease onset.<ref name="Larson2010" /><ref name="BarnesBook2005" /> The presence of HPV in the respiratory tract does not necessarily result in the development of laryngeal papillomatosis. Other factors that could be involved include immunodeficiency or other similar infections. For example, laryngeal papillomatosis may become more aggressive due to the presence of certain viruses (e.g., [[herpes simplex virus]], [[Epstein–Barr virus]]).<ref name="Carifi2015" />


The disease is typically separated into two forms, juvenile and adult papillomatosis, based on whether it develops before or after 20 years of age.<ref name="IARC" /><ref name="Fortes2017" /> The juvenile form is generally transmitted through contact with a mother's infected vaginal canal during childbirth.<ref name="BarnesBook2005">{{Cite book|title=Pathology and genetics of head and neck tumours|last=Barnes|first=Leon|publisher=IARC Press Lyon|year=2005|isbn=|location=|pages=144–145|url=https://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb9/BB9.pdf}}</ref> Less is known about transmission in the adult form of this disease, though [[oral sex]] has been implicated as a potential mode of transmission.<ref name="Larson2010" /><ref name="BarnesBook2005" /> However, it is uncertain whether oral sex would directly transmit the virus<ref name="BarnesBook2005" /> or activate the dormant virus that was transmitted at childbirth.<ref name="BarnesBook2005" /><ref name="Larson2010" />
The disease occurs in two forms, juvenile and adult papillomatosis, based on whether it develops before or after 20 years of age.<ref name="IARC" /><ref name="Fortes2017" /> The juvenile form is generally transmitted through contact with a mother's infected vaginal canal during childbirth.<ref name="BarnesBook2005">{{Cite book|title=Pathology and genetics of head and neck tumours| vauthors = Barnes L |publisher=IARC Press Lyon|year=2005|pages=144–145|url=https://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb9/BB9.pdf}}</ref> Less is known about transmission in the adult form of this disease, though [[oral sex]] has been implicated as a potential mode of transmission.<ref name="Larson2010" /><ref name="BarnesBook2005" /> However, it is uncertain whether oral sex would directly transmit the virus<ref name="BarnesBook2005" /> or activate the dormant virus that was transmitted at childbirth.<ref name="BarnesBook2005" /><ref name="Larson2010" />


In general, physicians are unsure why only certain people who have been exposed to the HPV types implicated in the disease develop laryngeal papillomatosis. In the case of the juvenile form of the disease, the likelihood of a child born of an infected mother developing laryngeal papillomatosis is low (between 1 in 231 to 1 in 400),<ref name=Derkay2008>{{Cite journal|last1=Derkay|first1=Craig S.|last2=Wiatrak|first2=Brian|date=July 2008|title=Recurrent respiratory papillomatosis: a review|journal=The Laryngoscope|volume=118|issue=7|pages=1236–1247|doi=10.1097/MLG.0b013e31816a7135|issn=1531-4995|pmid=18496162}}</ref> even if the mother's infection is active.<ref name=Larson2010/> Risk factors for a higher likelihood of transmission at childbirth include the first birth, vaginal birth, and teenage mother.<ref name=BarnesBook2005/><ref name=Larson2010/>
In general, physicians are unsure why only certain people who have been exposed to the HPV types implicated in the disease develop laryngeal papillomatosis. In the case of the juvenile form of the disease, the likelihood of a child born of an infected mother developing laryngeal papillomatosis is low (between 1 in 231 to 1 in 400),<ref name=Derkay2008>{{cite journal | vauthors = Derkay CS, Wiatrak B | title = Recurrent respiratory papillomatosis: a review | journal = The Laryngoscope | volume = 118 | issue = 7 | pages = 1236–1247 | date = July 2008 | pmid = 18496162 | doi = 10.1097/MLG.0b013e31816a7135 | s2cid = 12467098 }}</ref> even if the mother's infection is active.<ref name=Larson2010/> Risk factors for a higher likelihood of transmission at childbirth include the first birth, vaginal birth, and teenaged mother.<ref name=BarnesBook2005/><ref name=Larson2010/>


There are three big risk factors that contribute to the acquirement of the juvenile variant. These include:<ref>{{Cite journal|last1=Niyibizi|first1=Joseph|last2=Rodier|first2=Caroline|last3=Wassef|first3=Maggy|last4=Trottier|first4=Helen|date=2014|title=Risk factors for the development and severity of juvenile-onset recurrent respiratory papillomatosis: A systematic review|journal=International Journal of Pediatric Otorhinolaryngology|volume=78|issue=2|pages=186–197|doi=10.1016/j.ijporl.2013.11.036|pmid=24367938|issn=0165-5876}}</ref>
Three major risk factors affect the acquisition of the juvenile variant. These include:<ref>{{cite journal | vauthors = Niyibizi J, Rodier C, Wassef M, Trottier H | title = Risk factors for the development and severity of juvenile-onset recurrent respiratory papillomatosis: a systematic review | journal = International Journal of Pediatric Otorhinolaryngology | volume = 78 | issue = 2 | pages = 186–197 | date = February 2014 | pmid = 24367938 | doi = 10.1016/j.ijporl.2013.11.036 }}</ref>
* Birth history (e.g., increased time spent in vaginal delivery) and the presence of HPV in the vaginal canal. It is important to note that it is still uncertain whether caesarean delivery is a protective factor.
* Birth history (e.g., increased time spent in vaginal delivery) and the presence of HPV in the vaginal canal. It is important to note that it is still uncertain whether caesarean delivery is a protective factor.
* Genotype of the HPV (e.g., HPV-11)
* Genotype of the HPV (e.g., HPV-11)
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==Diagnosis==
==Diagnosis==
Laryngeal papillomatosis can be diagnosed through visualization of the lesions using one of several [[Laryngoscopy|indirect laryngoscopy]] procedures.<ref name=GrimesBook2014>{{Cite book|title=Sexually Transmitted Disease : An Encyclopedia of Diseases, Prevention, Treatment, and Issues|last=|first=|publisher=Greenwood|year=2014|isbn=9781440801341|editor-last=Grimes, MD|editor-first=Jill|pages=401–403|chapter=Laryngeal Papillomatosis|oclc=880530919|editor-last2=Fagerberg, MD|editor-first2=Kristyn|editor-last3=Smith, MD|editor-first3=Lori}}</ref><ref name=NIDCD/> In indirect laryngoscopy, the tongue is pulled forward and a laryngeal mirror or a rigid scope is passed through the mouth to examine the larynx.<ref name="ColtonBook2011">{{Cite book|title=Understanding Voice Problems : A Physiological Perspective for Diagnosis and Treatment|last1=Colton|first1=Raymond H.|last2=Casper|first2=Janina K.|last3=Leonard|first3=Rebecca|publisher=Lippincott Williams & Wilkins|year=2011|isbn=9781609138745|edition=4th|location=Philadelphia, PA|pages=171–172, 224–228|oclc=660546194}}</ref><ref name=GrimesBook2014/> Another variation of indirect laryngoscopy involves passing a flexible scope, known as a [[fiberscope]] or [[endoscope]], through the nose and into the throat to visualize the larynx from above.<ref name=ColtonBook2011/><ref name=NIDCD/> This procedure is also called flexible fiberoptic laryngoscopy.<ref name=ColtonBook2011/>
Laryngeal papillomatosis can be diagnosed through visualization of the lesions using one of several [[Laryngoscopy|indirect laryngoscopy]] procedures.<ref name=GrimesBook2014>{{Cite book|title=Sexually Transmitted Disease : An Encyclopedia of Diseases, Prevention, Treatment, and Issues|publisher=Greenwood|year=2014|isbn=9781440801341| veditors = Grimes J, Fagerberg K, Smith L |pages=401–403|chapter=Laryngeal Papillomatosis|oclc=880530919}}</ref><ref name=NIDCD/> In indirect laryngoscopy, the tongue is pulled forward and a laryngeal mirror or a rigid scope is passed through the mouth to examine the larynx.<ref name="ColtonBook2011">{{Cite book|title=Understanding Voice Problems : A Physiological Perspective for Diagnosis and Treatment| vauthors = Colton RH, Casper JK, Leonard R |publisher=Lippincott Williams & Wilkins|year=2011|isbn=9781609138745|edition=4th|location=Philadelphia, PA|pages=171–172, 224–228|oclc=660546194}}</ref><ref name=GrimesBook2014/> Another variation of indirect laryngoscopy involves passing a flexible scope, known as a [[fiberscope]] or [[endoscope]], through the nose and into the throat to visualize the larynx from above.<ref name=ColtonBook2011/><ref name=NIDCD/> This procedure is also called flexible fiberoptic laryngoscopy.<ref name=ColtonBook2011/>


The appearance of papillomas has been described as multiple or rarely, single, white growths with a lumpy texture similar to cauliflower.<ref name=ColtonBook2011/><ref name=Fortes2017>{{cite journal|last1=Fortes|first1=HR|last2=von Ranke|first2=FM|last3=Escuissato|first3=DL|last4=Araujo Neto|first4=CA|last5=Zanetti|first5=G|last6=Hochhegger|first6=B|last7=Souza|first7=CA|last8=Marchiori|first8=E|title=Recurrent respiratory papillomatosis: A state-of-the-art review.|journal=Respiratory Medicine|date=May 2017|volume=126|pages=116–121|doi=10.1016/j.rmed.2017.03.030|pmid=28427542|doi-access=free}}</ref> Papillomas usually present in the larynx, especially on the [[vocal folds]] and in the space above the vocal folds called the [[Laryngeal ventricle|ventricles]].<ref name=WenigBook2013>{{Cite book|title=Diagnostic Histopathology of Tumors|last=Wenig|first=Bruce M.|date=2013|publisher=Saunders/Elsevier|others=Fletcher, Christopher D. M.|isbn=9781455737543|editor-last=Fletcher, MD|editor-first=Christopher D. M.|edition=4th|location=Philadelphia, PA|pages=92–98|chapter=Tumors of the Upper Respiratory Tract|oclc=846903109}}</ref><ref name=GrantBook2010>{{Cite book|title=Surgery of Larynx and Trachea|url=https://archive.org/details/surgerylarynxtra00rema|url-access=limited|last1=Grant|first1=David G.|last2=Mirchall|first2=Martin A.|last3=Bradley|first3=Patrick J.|publisher=Springer-Verlag Berlin Heidelberg|year=2010|isbn=9783540791355|editor-last=Remacle|editor-first=Marc|location=Berlin|pages=[https://archive.org/details/surgerylarynxtra00rema/page/n101 91]–112|chapter=Surgery for Benign Tumors of the Adult Larynx|oclc=567327912|editor-last2=Eckel|editor-first2=Hans Edmund}}</ref><ref name=IARC>{{Cite book|title=World Health Organization Classification of Head and Neck Tumours|publisher=International Agency for Research on Cancer|year=2017|isbn=9789283224389|editor-last=El-Naggar|editor-first=Adel K.|location=Lyon|pages=93–95|chapter=Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space|oclc=990147303|editor-last2=Chan|editor-first2=John K. C.|editor-last3=Grandis|editor-first3=Jennifer R.|editor-last4=Takashi|editor-first4=Takata|editor-last5=Slootweg|editor-first5=Pieter J.}}</ref> They can spread to other parts of the larynx and throughout the aerodigestive tract, from the mouth to the lower respiratory tract.<ref name=IARC/><ref name=Fortes2017/><ref name=WenigBook2013/> Spread to regions beyond the larynx is more common in children than adults.<ref name=WenigBook2013/> Growths tend to be located at normal junctions in [[squamous]] and [[Epithelium|ciliated epithelium]] or at tissue junctions arising from injury.<ref name=IARC/><ref name=WenigBook2013/><ref name=GrantBook2010/>
The appearance of papillomas has been described as multiple or rarely, single, white growths with a lumpy texture similar to cauliflower.<ref name=ColtonBook2011/><ref name=Fortes2017>{{cite journal | vauthors = Fortes HR, von Ranke FM, Escuissato DL, Araujo Neto CA, Zanetti G, Hochhegger B, Souza CA, Marchiori E | display-authors = 6 | title = Recurrent respiratory papillomatosis: A state-of-the-art review | journal = Respiratory Medicine | volume = 126 | pages = 116–121 | date = May 2017 | pmid = 28427542 | doi = 10.1016/j.rmed.2017.03.030 | doi-access = free | hdl = 10923/22484 | hdl-access = free }}</ref> Papillomas usually present in the larynx, especially on the [[vocal folds]] and in the space above the vocal folds called the [[Laryngeal ventricle|ventricles]].<ref name=WenigBook2013>{{Cite book|title=Diagnostic Histopathology of Tumors| vauthors = Wenig BM, Fletcher CD |date=2013|publisher=Saunders/Elsevier |isbn=9781455737543| veditors = Fletcher CD |edition=4th|location=Philadelphia, PA|pages=92–98|chapter=Tumors of the Upper Respiratory Tract|oclc=846903109}}</ref><ref name=GrantBook2010>{{Cite book|title=Surgery of Larynx and Trachea|url=https://archive.org/details/surgerylarynxtra00rema|url-access=limited| vauthors = Grant DG, Mirchall MA, Bradley PJ |publisher=Springer-Verlag Berlin Heidelberg|year=2010|isbn=9783540791355| veditors = Remacle M, Eckel HE |location=Berlin|pages=[https://archive.org/details/surgerylarynxtra00rema/page/n101 91]–112|chapter=Surgery for Benign Tumors of the Adult Larynx|oclc=567327912 }}</ref><ref name=IARC>{{Cite book|title=World Health Organization Classification of Head and Neck Tumours|publisher=International Agency for Research on Cancer|year=2017|isbn=9789283224389| veditors = El-Naggar AK, Chan JK, Grandis JR, Takashi T, Slootweg PJ |location=Lyon|pages=93–95|chapter=Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space|oclc=990147303}}</ref> They can spread to other parts of the larynx and throughout the aerodigestive tract, from the mouth to the lower respiratory tract.<ref name=IARC/><ref name=Fortes2017/><ref name=WenigBook2013/> Spread to regions beyond the larynx is more common in children than adults.<ref name=WenigBook2013/> Growths tend to be located at normal junctions in [[squamous]] and [[Epithelium|ciliated epithelium]] or at tissue junctions arising from injury.<ref name=IARC/><ref name=WenigBook2013/><ref name=GrantBook2010/>


A [[confirmatory diagnosis]] of laryngeal papillomatosis can only be obtained through a [[biopsy]], involving microscopic examination and HPV testing of a sample of the growth.<ref name=Fortes2017/><ref name=GrimesBook2014/> Biopsy samples are collected under [[General anaesthesia|general anesthesia]], either through [[Direct Laryngoscopy|direct laryngoscopy]] or [[Bronchoscopy|fiberoptic bronchoscopy]].<ref name=GrimesBook2014/><ref name=Fortes2017/>
A [[confirmatory diagnosis]] of laryngeal papillomatosis can only be obtained through a [[biopsy]], involving microscopic examination and HPV testing of a sample of the growth.<ref name=Fortes2017/><ref name=GrimesBook2014/> Biopsy samples are collected under [[General anaesthesia|general anesthesia]], either through [[Direct Laryngoscopy|direct laryngoscopy]] or [[Bronchoscopy|fiberoptic bronchoscopy]].<ref name=GrimesBook2014/><ref name=Fortes2017/>


== Prevention ==
== Prevention ==
Little is known in terms of effective means of prevention, if the mother is infected with HPV. ([[HPV vaccination]] can prevent these infections in the mother, and thereby eliminate the possibility of the virus [[Vertically transmitted infection|infecting the baby]].<ref name=":1">{{Cite journal|last1=Ivancic|first1=Ryan|last2=Iqbal|first2=Hassan|last3=deSilva|first3=Brad|last4=Pan|first4=Quintin|last5=Matrka|first5=Laura|date=February 2018|title=Current and future management of recurrent respiratory papillomatosis|journal=Laryngoscope Investigative Otolaryngology|volume=3|issue=1|pages=22–34|doi=10.1002/lio2.132|issn=2378-8038|pmc=5824106|pmid=29492465}}</ref>) Due to the low likelihood of transmission even from an infected mother, it is not recommended to expose the mother and child to the additional risks of [[caesarean section]] to prevent the transmission of this disease during vaginal childbirth.<ref name=Larson2010>{{Cite journal|last1=Larson|first1=Daniel A.|last2=Derkay|first2=Craig S.|date=June 2010|title=Epidemiology of recurrent respiratory papillomatosis|journal=[[APMIS]]|volume=118|issue=6–7|pages=450–454|doi=10.1111/j.1600-0463.2010.02619.x|issn=1600-0463|pmid=20553527}}</ref> Opting for a caesarean section does not guarantee that transmission will not still occur.<ref name=BarnesBook2005/>
Little is known in terms of effective means of prevention, if the mother is infected with HPV. ([[HPV vaccination]] can prevent these infections in the mother, and thereby eliminate the possibility of the virus [[Vertically transmitted infection|infecting the baby]].<ref name=":1">{{cite journal | vauthors = Ivancic R, Iqbal H, deSilva B, Pan Q, Matrka L | title = Current and future management of recurrent respiratory papillomatosis | journal = Laryngoscope Investigative Otolaryngology | volume = 3 | issue = 1 | pages = 22–34 | date = February 2018 | pmid = 29492465 | pmc = 5824106 | doi = 10.1002/lio2.132 }}</ref>) Due to the low likelihood of transmission even from an infected mother, it is not recommended to expose the mother and child to the additional risks of [[caesarean section]] to prevent the transmission of this disease during vaginal childbirth.<ref name=Larson2010>{{cite journal | vauthors = Larson DA, Derkay CS | title = Epidemiology of recurrent respiratory papillomatosis | journal = APMIS | volume = 118 | issue = 6–7 | pages = 450–454 | date = June 2010 | pmid = 20553527 | doi = 10.1111/j.1600-0463.2010.02619.x | s2cid = 193686 | doi-access = free }}</ref> Opting for a caesarean section does not guarantee that transmission will not still occur.<ref name=BarnesBook2005/>


== Treatment ==
== Treatment ==


As of 2014 there was no permanent cure for laryngeal papillomatosis, and treatment options aimed to remove and limit the recurrence of the papillomas.<ref name=Alfano2014>{{cite journal|last1=Alfano|first1=DM|title=Human papillomavirus laryngeal tracheal papillomatosis.|journal=Journal of Pediatric Health Care |date=2014|volume=28|issue=5|pages=451–5|doi=10.1016/j.pedhc.2014.04.003|pmid=24882788}}</ref> Repeated treatments are often needed because of the recurrent nature of the virus, especially for children, as the juvenile form of laryngeal papillomatosis often triggers more aggressive relapses than the adult form.<ref name=Alfano2014/><ref name=Carifi2015>{{cite journal|last1=Carifi|first1=M|last2=Napolitano|first2=D|last3=Morandi|first3=M|last4=Dall'Olio|first4=D|title=Recurrent respiratory papillomatosis: current and future perspectives.|journal=Therapeutics and Clinical Risk Management|date=2015|volume=11|pages=731–8|doi=10.2147/TCRM.S81825|pmid=25999724|pmc=4427257}}</ref><ref name=Fortes2017/><ref name=Avelino2013>{{Cite journal|last1=Avelino|first1=Melissa Ameloti Gomes|last2=Zaiden|first2=Tallyta Campos Domingues Teixeira|last3=Gomes|first3=Raquel Oliveira|date=September 2013|title=Surgical treatment and adjuvant therapies of recurrent respiratory papillomatosis|journal=Brazilian Journal of Otorhinolaryngology|volume=79|issue=5|pages=636–642|doi=10.5935/1808-8694.20130114|issn=1808-8686|pmid=24141682|doi-access=free}}</ref> Between recurrences, [[voice therapy]] may be used to restore or maintain the person's voice function.<ref name=ColtonBook2011/>
As of 2014, there was no permanent cure for laryngeal papillomatosis, and treatment options aimed to remove and limit the recurrence of the papillomas.<ref name=Alfano2014>{{cite journal | vauthors = Alfano DM | title = Human papillomavirus laryngeal tracheal papillomatosis | journal = Journal of Pediatric Health Care | volume = 28 | issue = 5 | pages = 451–455 | date = 2014 | pmid = 24882788 | doi = 10.1016/j.pedhc.2014.04.003 }}</ref> Repeated treatments are often needed because of the recurrent nature of the virus, especially for children, as the juvenile form of laryngeal papillomatosis often triggers more aggressive relapses than the adult form.<ref name=Alfano2014/><ref name=Carifi2015>{{cite journal | vauthors = Carifi M, Napolitano D, Morandi M, Dall'Olio D | title = Recurrent respiratory papillomatosis: current and future perspectives | journal = Therapeutics and Clinical Risk Management | volume = 11 | pages = 731–738 | date = 2015 | pmid = 25999724 | pmc = 4427257 | doi = 10.2147/TCRM.S81825 | doi-access = free }}</ref><ref name=Fortes2017/><ref name=Avelino2013>{{cite journal | vauthors = Avelino MA, Zaiden TC, Gomes RO | title = Surgical treatment and adjuvant therapies of recurrent respiratory papillomatosis | journal = Brazilian Journal of Otorhinolaryngology | volume = 79 | issue = 5 | pages = 636–642 | date = September 2013 | pmid = 24141682 | doi = 10.5935/1808-8694.20130114 | pmc = 9442437 | doi-access = free }}</ref> Between recurrences, [[voice therapy]] may be used to restore or maintain the person's voice function.<ref name=ColtonBook2011/>


=== Surgery ===
=== Surgery ===
The first line of treatment is surgery to remove papillomas.<ref name=Fortes2017/><ref name=Avelino2013/> Typically performed using a laryngeal endoscopy, surgery can protect intact tissues and the individual's voice, as well as ensure that the airway remains unobstructed by the disease.<ref name="Carifi2015" /> However, surgery does not prevent recurrences, and can lead to a number of serious complications.<ref name=Alfano2014/><ref name=Fortes2017/><ref name="Avelino2013"/> Laser technology, and [[Carbon dioxide laser|carbon dioxide laser surgery]] in particular, has been used since the 1970s for the removal of papillomas; however, laser surgery is not without its risks, and has been associated with a higher occurrence of respiratory tract burns, [[stenosis]], severe laryngeal scarring, and [[Fistula|tracheoesophagyeal fistulae]].<ref name=Alfano2014/><ref name=Carifi2015/><ref name=Fortes2017/><ref name=Avelino2013/> [[Tracheotomy|Tracheotomies]] are offered for the most aggressive cases, where multiple debulking surgery failures have led to airways being compromised.<ref name=Carifi2015/><ref name=Fortes2017/> The tracheotomies use [[Tracheal tube|breathing tubes]] to reroute air around the affected area, thereby restoring the person's breathing function. Although this intervention is usually temporary, some people must use the tube indefinitely.<ref name=NIDCD/> This method should be avoided if at all possible, since the breathing tube may serve as a conduit for spread of the disease as far down as the tracheobronchal tree.<ref name=Carifi2015/><ref name=Fortes2017/>
The first line of treatment is surgery to remove papillomas.<ref name=Fortes2017/><ref name=Avelino2013/> Typically performed using a laryngeal endoscopy, surgery can protect intact tissues and the individual's voice, as well as ensure that the airway remains unobstructed by the disease.<ref name="Carifi2015" /> However, surgery does not prevent recurrences, and can lead to a number of serious complications.<ref name=Alfano2014/><ref name=Fortes2017/><ref name="Avelino2013"/> Laser technology, and [[Carbon dioxide laser|carbon dioxide laser surgery]] in particular, has been used since the 1970s for the removal of papillomas; however, laser surgery is not without its risks, and has been associated with a higher occurrence of respiratory tract burns, [[stenosis]], severe laryngeal scarring, and [[Fistula|tracheoesophagyeal fistulae]].<ref name=Alfano2014/><ref name=Carifi2015/><ref name=Fortes2017/><ref name=Avelino2013/> [[Tracheotomy|Tracheotomies]] are offered for the most aggressive cases, where multiple debulking surgery failures have led to airways being compromised.<ref name=Carifi2015/><ref name=Fortes2017/> The tracheotomies use [[Tracheal tube|breathing tubes]] to reroute air around the affected area, thereby restoring the person's breathing function. Although this intervention is usually temporary, some people must use the tube indefinitely.<ref name=NIDCD/> This method should be avoided if at all possible, since the breathing tube may serve as a conduit for spread of the disease as far down as the [[tracheobronchial tree]].<ref name=Carifi2015/><ref name=Fortes2017/>


A microdebrider is a tool that can suction tissue into a blade, which then cuts the tissue. Microdebriders are gradually replacing laser technology as the treatment of choice for laryngeal papillomatosis, due to their ability to selectively suction papillomas while relatively sparing unaffected tissue.<ref name=Carifi2015/><ref name=Avelino2013/> In addition to the lower risk of complications, microdebrider surgery also is reportedly less expensive, less time-consuming, and more likely to give the person a better voice quality than the traditional laser surgery approaches.<ref name=Avelino2013/>
A microdebrider is a tool that can suction tissue into a blade, which then cuts the tissue. Microdebriders are gradually replacing laser technology as the treatment of choice for laryngeal papillomatosis, due to their ability to selectively suction papillomas while relatively sparing unaffected tissue.<ref name=Carifi2015/><ref name=Avelino2013/> In addition to the lower risk of complications, microdebrider surgery also is reportedly less expensive, less time-consuming, and more likely to give the person a better voice quality than the traditional laser surgery approaches.<ref name=Avelino2013/>


=== Nonsurgical adjuvant treatment ===
=== Nonsurgical adjuvant treatment ===
For about 20% of people, surgery is not sufficient to control their laryngeal papillomatosis, and additional nonsurgical and/or medical treatments are necessary.<ref name=Fortes2017/> {{As of|2015}}, these treatments alone are not sufficient to cure laryngeal papillomatosis, and can only be considered supplemental to surgery.<ref name=Carifi2015/> Some varieties of nonsurgical treatments include [[interferon]], [[antiviral drug]]s (especially [[cidofovir]], but also [[ribavirin]] and [[Aciclovir|acyclovir]]), and [[photodynamic therapy]].<ref name=Alfano2014/><ref name=Carifi2015/><ref name=Fortes2017/><ref name=Avelino2013/><ref name=ColtonBook2011/> The monoclonal antibody against Vascular Endothelial Growth Factor ([[VEGF]]), [[Bevacizumab]] has shown promising result as an adjuvant therapy in the management of recurrent respiratory papillomatosis.<ref>Mohr M, Schliemann C, Biermann C, Schmidt L-H, Kessler T, Schmidt J, et al. [https://www.ncbi.nlm.nih.gov/pubmed/25289079 Rapid response to systemic bevacizumab therapy in recurrent respiratory papillomatosis.] Oncol Lett. 2014 Nov;8(5):1912–8.</ref><ref>Sidell DR, Nassar M, Cotton RT, Zeitels SM, de Alarcon A. [https://www.ncbi.nlm.nih.gov/pubmed/24633948 High-dose sublesional bevacizumab (avastin) for pediatric recurrent respiratory papillomatosis]. Ann Otol Rhinol Laryngol. 2014 Mar;123(3):214–21.</ref>
For about 20% of people, surgery is not sufficient to control their laryngeal papillomatosis, and additional nonsurgical and/or medical treatments are necessary.<ref name=Fortes2017/> {{As of|2015}}, these treatments alone are not sufficient to cure laryngeal papillomatosis, and can only be considered supplemental to surgery.<ref name=Carifi2015/> Some varieties of nonsurgical treatments include [[interferon]], [[antiviral drug]]s (especially [[cidofovir]], but also [[ribavirin]] and [[Aciclovir|acyclovir]]), and [[photodynamic therapy]].<ref name=Alfano2014/><ref name=Carifi2015/><ref name=Fortes2017/><ref name=Avelino2013/><ref name=ColtonBook2011/> The monoclonal antibody against [[vascular endothelial growth factor]] (VEGF), [[bevacizumab]], has shown promising result as an adjuvant therapy in the management of recurrent respiratory papillomatosis.<ref>Mohr M, Schliemann C, Biermann C, Schmidt L-H, Kessler T, Schmidt J, et al. [https://www.ncbi.nlm.nih.gov/pubmed/25289079 Rapid response to systemic bevacizumab therapy in recurrent respiratory papillomatosis.] Oncol Lett. 2014 Nov;8(5):1912–8.</ref><ref>Sidell DR, Nassar M, Cotton RT, Zeitels SM, de Alarcon A. [https://www.ncbi.nlm.nih.gov/pubmed/24633948 High-dose sublesional bevacizumab (avastin) for pediatric recurrent respiratory papillomatosis]. Ann Otol Rhinol Laryngol. 2014 Mar;123(3):214–21.</ref>


Although vaccines are normally used to prevent infections from happening, [[HPV vaccine|HPV vaccines]] can be used therapeutically (after the infection has occurred).<ref name=":2">{{Cite journal|last1=Derkay|first1=Craig S.|last2=Bluher|first2=Andrew E.|s2cid=52947478|date=December 2018|title=Recurrent respiratory papillomatosis: update 2018|journal=Current Opinion in Otolaryngology & Head and Neck Surgery|volume=26|issue=6|pages=421–425|doi=10.1097/MOO.0000000000000490|issn=1531-6998|pmid=30300210}}</ref><ref name=":3">{{Cite journal|last1=Pham|first1=Christine T.|last2=Juhasz|first2=Margit|last3=Sung|first3=Calvin|last4=Mesinkovska|first4=Natasha Atanaskova|title=The Human Papillomavirus Vaccine as a Treatment 1 for HPV-related Dysplastic and Neoplastic Conditions: A Literature Review|journal=Journal of the American Academy of Dermatology|volume=82|issue=1|pages=202–212|doi=10.1016/j.jaad.2019.04.067|issn=1097-6787|pmid=31085272|year=2020}}</ref> For most patients, the HPV vaccine significantly increases the length of time needed between surgeries.<ref name=":1" /><ref name=":2" /><ref name=":3" />
Although vaccines are normally used to prevent infections from happening, [[HPV vaccine]]s can be used therapeutically (after the infection has occurred).<ref name=":2">{{cite journal | vauthors = Derkay CS, Bluher AE | title = Recurrent respiratory papillomatosis: update 2018 | journal = Current Opinion in Otolaryngology & Head and Neck Surgery | volume = 26 | issue = 6 | pages = 421–425 | date = December 2018 | pmid = 30300210 | doi = 10.1097/MOO.0000000000000490 | s2cid = 52947478 }}</ref><ref name=":3">{{cite journal | vauthors = Pham CT, Juhasz M, Sung CT, Mesinkovska NA | title = The human papillomavirus vaccine as a treatment for human papillomavirus-related dysplastic and neoplastic conditions: A literature review | journal = Journal of the American Academy of Dermatology | volume = 82 | issue = 1 | pages = 202–212 | date = January 2020 | pmid = 31085272 | doi = 10.1016/j.jaad.2019.04.067 | s2cid = 155092723 }}</ref> For most patients, the HPV vaccine significantly increases the length of time needed between surgeries.<ref name=":1" /><ref name=":2" /><ref name=":3" />


== Outcomes ==
{{Anchor|Outcomes}}
⚫
The evolution of laryngeal papillomatosis is highly unpredictable and is characterized by modulation of its severity and variable rate of progression across individuals.<ref name="MehtaBook2016" /><ref name=IARC/> While instances of total recovery are observed, the condition is often persistent and lesions can reappear even after treatment.<ref name="NIDCD" /><ref name=IARC/><ref name=":0">{{Cite journal|last1=Drejet|first1=Sarah|last2=Halum|first2=Stacey|last3=Brigger|first3=Matthew|last4=Skopelja|first4=Elaine|last5=Parker|first5=Noah P.|s2cid=4406970|date=March 2017|title=A Systematic Review|journal=Otolaryngology–Head and Neck Surgery|volume=156|issue=3|pages=435–441|doi=10.1177/0194599816683384|issn=1097-6817|pmid=28072562}}</ref> Factors that might affect the clinical course of the condition include: the [[Human papillomavirus infection|HPV]] genotype, the age at onset, the elapsed time between the diagnosis and first treatment in addition to previous medical procedures.<ref name="Fortes2017" /><ref name=WenigBook2013/><ref name=IARC/> Other factors, albeit controversial, such as smoking or the presence of [[gastroesophageal reflux disease]] might also play a role in the progression of the disease.<ref name=WenigBook2013/><ref name="Taliercio2015">{{Cite journal|last1=Taliercio|first1=Sal|last2=Cespedes|first2=Michelle|last3=Born|first3=Hayley|last4=Ruiz|first4=Ryan|last5=Roof|first5=Scott|last6=Amin|first6=Milan R.|last7=Branski|first7=Ryan C.|date=January 2015|title=Adult-onset recurrent respiratory papillomatosis: a review of disease pathogenesis and implications for patient counseling|journal=JAMA Otolaryngology–Head & Neck Surgery|volume=141|issue=1|pages=78–83|doi=10.1001/jamaoto.2014.2826|issn=2168-619X|pmid=25393901}}</ref>


== Prognosis ==
⚫
The [[papilloma]]s can travel past the [[larynx]] and infect extralaryngeal sites.<ref name=MehtaBook2016/> In more aggressive cases, infection of the [[lung]]s can occur with progressive airway obstruction.<ref name=MehtaBook2016/><ref name=Venkatesan2012/> Although rare (less than 1% of people with laryngeal papillomatosis), transformation from a benign form to a malignant form is also observed.<ref name=MehtaBook2016/><ref name=Venkatesan2012/> Death can result from these complications (morbidity rate is around 1-2%).<ref name="MehtaBook2016" />
⚫
The evolution of laryngeal papillomatosis is highly unpredictable and is characterized by modulation of its severity and variable rate of progression across individuals.<ref name="MehtaBook2016" /><ref name=IARC/> While instances of total recovery are observed, the condition is often persistent and lesions can reappear even after treatment.<ref name="NIDCD" /><ref name=IARC/><ref name=":0">{{cite journal | vauthors = Drejet S, Halum S, Brigger M, Skopelja E, Parker NP | title = A Systematic Review | journal = Otolaryngology–Head and Neck Surgery | volume = 156 | issue = 3 | pages = 435–441 | date = March 2017 | pmid = 28072562 | doi = 10.1177/0194599816683384 | s2cid = 4406970 }}</ref> Factors that might affect the clinical course of the condition include: the [[Human papillomavirus infection|HPV]] genotype, the age at onset, the elapsed time between the diagnosis and first treatment in addition to previous medical procedures.<ref name="Fortes2017" /><ref name=WenigBook2013/><ref name=IARC/> Other factors, albeit controversial, such as smoking or the presence of [[gastroesophageal reflux disease]] might also play a role in the progression of the disease.<ref name=WenigBook2013/><ref name="Taliercio2015">{{cite journal | vauthors = Taliercio S, Cespedes M, Born H, Ruiz R, Roof S, Amin MR, Branski RC | title = Adult-onset recurrent respiratory papillomatosis: a review of disease pathogenesis and implications for patient counseling | journal = JAMA Otolaryngology–Head & Neck Surgery | volume = 141 | issue = 1 | pages = 78–83 | date = January 2015 | pmid = 25393901 | doi = 10.1001/jamaoto.2014.2826 }}</ref>

⚫
The [[papilloma]]s can travel past the [[larynx]] and infect extralaryngeal sites.<ref name=MehtaBook2016/> In more aggressive cases, infection of the [[lung]]s can occur with progressive airway obstruction.<ref name=MehtaBook2016/><ref name=Venkatesan2012/> Although rare (less than 1% of people with laryngeal papillomatosis), transformation from a benign form to a malignant form is also observed.<ref name=MehtaBook2016/><ref name=Venkatesan2012/> Death can result from these complications (morbidity rate is around 1–2%).<ref name="MehtaBook2016" />


== Epidemiology ==
== Epidemiology ==
Laryngeal papillomatosis is a rare disease with a [[bimodal distribution]] based on age of [[Incidence (epidemiology)|incidence]].<ref name=IARC/> The incidence, or number of new cases, of laryngeal papillomatosis cases is at approximately 4.3 cases per 100 000 children and 1.8 cases per 100 000 adults annually.<ref name=Fortes2017/><ref name=GrimesBook2014/><ref name=ColtonBook2011/><ref name=IARC/> The incidence of laryngeal papillomatosis in children peaks before the age of 5, though the term juvenile papillomatosis refers to all cases occurring before the age of 20.<ref name=IARC/><ref name=Fortes2017/> The incidence of adult laryngeal papillomatosis, which has an onset after the age of 20, peaks between the ages of 20 and 40.<ref name=Fortes2017/><ref name=IARC/> While there are no gender differences in the incidence of laryngeal papillomatosis in children, adult laryngeal papillomatosis occurs more frequently in males than in females.<ref name=Fortes2017/><ref name=WenigBook2013/><ref name=IARC/> The incidence of laryngeal papillomatosis also varies according to factors such as socioeconomic status, such that higher rates are observed in groups having a lower socioeconomic status.<ref name=Fortes2017/>
Laryngeal papillomatosis is a rare disease with a [[bimodal distribution]] based on age of [[Incidence (epidemiology)|incidence]].<ref name=IARC/> The incidence, or number of new cases, of laryngeal papillomatosis cases is at approximately 4.3 cases per 100,000 children and 1.8 cases per 100,000 adults annually.<ref name=Fortes2017/><ref name=GrimesBook2014/><ref name=ColtonBook2011/><ref name=IARC/> The incidence of laryngeal papillomatosis in children peaks before the age of 5, though the term juvenile papillomatosis refers to all cases occurring before the age of 20.<ref name=IARC/><ref name=Fortes2017/> The incidence of adult laryngeal papillomatosis, which has an onset after the age of 20, peaks between the ages of 20 and 40.<ref name=Fortes2017/><ref name=IARC/> While there are no gender differences in the incidence of laryngeal papillomatosis in children, adult laryngeal papillomatosis occurs more frequently in males than in females.<ref name=Fortes2017/><ref name=WenigBook2013/><ref name=IARC/> The incidence of laryngeal papillomatosis also varies according to factors such as socioeconomic status, such that higher rates are observed in groups having a lower socioeconomic status.<ref name=Fortes2017/>


==Costs==
==Costs==
Because of its relative commonness and the cost of treatments, more money is spent on treating RRP than any other benign airway tumor.<ref name=":2" />
Because of its relative commonness and the cost of treatments, more money is spent on treating RRP than on any other benign airway tumor.<ref name=":2" />


==Research==
==Research==
As of 2015 use of the [[MMR vaccine|measles-mumps-rubella vaccine]] to reduce rate of recurrences had been investigated, but had not yielded significant results.<ref name=Carifi2015/>
As of 2015, use of the [[MMR vaccine|measles–mumps–rubella vaccine]] to reduce rate of recurrences had been investigated, but had not yielded significant results.<ref name=Carifi2015/>


== See also ==
== See also ==
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| Orphanet = 60032
| Orphanet = 60032
}}
}}

{{Viral cutaneous conditions}}
{{Viral cutaneous conditions}}
{{Respiratory neoplasia}}
{{Respiratory neoplasia}}
{{Human papillomavirus}}
{{Human papillomavirus}}
{{Authority control}}


{{DEFAULTSORT:Laryngeal Papillomatosis}}
{{DEFAULTSORT:Laryngeal Papillomatosis}}
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[[Category:Virus-related cutaneous conditions]]
[[Category:Virus-related cutaneous conditions]]
[[Category:Head and neck cancer of respiratory tract]]
[[Category:Head and neck cancer of respiratory tract]]
[[Category:Larynx disorders]]

Latest revision as of 17:10, 18 April 2024

Laryngeal papillomatosis
Other namesAdult papillomatosis, Juvenile papillomatosis, Recurrent respiratory papillomatosis (RRP), Squamous cell papillomatosis, Nonkeratinized papillomatosis
Volumetric CT rendering of multiple tracheal papilloma (arrow)
SpecialtyOtorhinolaryngology Edit this on Wikidata
ComplicationsSquamous cell carcinoma
CausesHPV infection

Laryngeal papillomatosis, also known as recurrent respiratory papillomatosis (RRP) or glottal papillomatosis, is a rare medical condition in which benign tumors (papilloma) form along the aerodigestive tract.[1][2] There are two variants based on the age of onset: juvenile and adult laryngeal papillomatosis.[3] The tumors are caused by human papillomavirus (HPV) infection of the throat. The tumors may lead to narrowing of the airway, which may cause vocal changes or airway obstruction.[4][5] Laryngeal papillomatosis is initially diagnosed through indirect laryngoscopy upon observation of growths on the larynx and can be confirmed through a biopsy.[6][7][8] Treatment for laryngeal papillomatosis aims to remove the papillomas and limit their recurrence.[9] Due to the recurrent nature of the virus, repeated treatments usually are needed.[7][9][2][10] Laryngeal papillomatosis is primarily treated surgically, though supplemental nonsurgical and/or medical treatments may be considered in some cases.[7][10] The evolution of laryngeal papillomatosis is highly variable.[4][1] Though total recovery may be observed, it is often persistent despite treatment.[11][8][1] The number of new cases of laryngeal papillomatosis cases is approximately 4.3 cases per 100,000 children and 1.8 cases per 100,000 adults annually.[1][6][7][12]

Signs and symptoms[edit]

A common symptom of laryngeal papillomatosis is a change in voice quality. More specifically, hoarseness is observed.[4][5] As a consequence of the narrowing of the laryngeal or tracheal parts of the airway, shortness of breath, chronic cough and stridor (i.e. noisy breathing which can sound like a whistle or a snore), can be present.[4][5] As the disease progresses, occurrence of secondary symptoms such as dysphagia, pneumonia, acute respiratory distress syndrome, failure to thrive, and recurrent upper respiratory infections can be diagnosed.[4][5] The risk of laryngeal papillomatosis spreading to the lungs is higher in the juvenile-onset than the adult-onset.[3] In children, symptoms are usually more severe and often mistaken for manifestations of other diseases such as asthma, croup or bronchitis. Therefore, diagnosis is usually delayed.[8][5]

Cause[edit]

Laryngeal papillomatosis is caused by human papillomavirus (HPV) infection, most frequently types 6 and 11,[13] although genotypes 16, 18, 31, and 33 have also been implicated.[7] HPV-11 is associated with more aggressive forms of papillomatosis, which may involve more distal parts of the tracheobronchial tree.[7] The mode of viral inoculation is hypothesized to vary according to age of disease onset.[13][14] The presence of HPV in the respiratory tract does not necessarily result in the development of laryngeal papillomatosis. Other factors that could be involved include immunodeficiency or other similar infections. For example, laryngeal papillomatosis may become more aggressive due to the presence of certain viruses (e.g., herpes simplex virus, Epstein–Barr virus).[2]

The disease occurs in two forms, juvenile and adult papillomatosis, based on whether it develops before or after 20 years of age.[1][7] The juvenile form is generally transmitted through contact with a mother's infected vaginal canal during childbirth.[14] Less is known about transmission in the adult form of this disease, though oral sex has been implicated as a potential mode of transmission.[13][14] However, it is uncertain whether oral sex would directly transmit the virus[14] or activate the dormant virus that was transmitted at childbirth.[14][13]

In general, physicians are unsure why only certain people who have been exposed to the HPV types implicated in the disease develop laryngeal papillomatosis. In the case of the juvenile form of the disease, the likelihood of a child born of an infected mother developing laryngeal papillomatosis is low (between 1 in 231 to 1 in 400),[15] even if the mother's infection is active.[13] Risk factors for a higher likelihood of transmission at childbirth include the first birth, vaginal birth, and teenaged mother.[14][13]

Three major risk factors affect the acquisition of the juvenile variant. These include:[16]

  • Birth history (e.g., increased time spent in vaginal delivery) and the presence of HPV in the vaginal canal. It is important to note that it is still uncertain whether caesarean delivery is a protective factor.
  • Genotype of the HPV (e.g., HPV-11)
  • Individual factors (e.g., being younger when diagnosed, which may be due to a less developed immune system).

Diagnosis[edit]

Laryngeal papillomatosis can be diagnosed through visualization of the lesions using one of several indirect laryngoscopy procedures.[6][8] In indirect laryngoscopy, the tongue is pulled forward and a laryngeal mirror or a rigid scope is passed through the mouth to examine the larynx.[12][6] Another variation of indirect laryngoscopy involves passing a flexible scope, known as a fiberscope or endoscope, through the nose and into the throat to visualize the larynx from above.[12][8] This procedure is also called flexible fiberoptic laryngoscopy.[12]

The appearance of papillomas has been described as multiple or rarely, single, white growths with a lumpy texture similar to cauliflower.[12][7] Papillomas usually present in the larynx, especially on the vocal folds and in the space above the vocal folds called the ventricles.[17][18][1] They can spread to other parts of the larynx and throughout the aerodigestive tract, from the mouth to the lower respiratory tract.[1][7][17] Spread to regions beyond the larynx is more common in children than adults.[17] Growths tend to be located at normal junctions in squamous and ciliated epithelium or at tissue junctions arising from injury.[1][17][18]

A confirmatory diagnosis of laryngeal papillomatosis can only be obtained through a biopsy, involving microscopic examination and HPV testing of a sample of the growth.[7][6] Biopsy samples are collected under general anesthesia, either through direct laryngoscopy or fiberoptic bronchoscopy.[6][7]

Prevention[edit]

Little is known in terms of effective means of prevention, if the mother is infected with HPV. (HPV vaccination can prevent these infections in the mother, and thereby eliminate the possibility of the virus infecting the baby.[19]) Due to the low likelihood of transmission even from an infected mother, it is not recommended to expose the mother and child to the additional risks of caesarean section to prevent the transmission of this disease during vaginal childbirth.[13] Opting for a caesarean section does not guarantee that transmission will not still occur.[14]

Treatment[edit]

As of 2014, there was no permanent cure for laryngeal papillomatosis, and treatment options aimed to remove and limit the recurrence of the papillomas.[9] Repeated treatments are often needed because of the recurrent nature of the virus, especially for children, as the juvenile form of laryngeal papillomatosis often triggers more aggressive relapses than the adult form.[9][2][7][10] Between recurrences, voice therapy may be used to restore or maintain the person's voice function.[12]

Surgery[edit]

The first line of treatment is surgery to remove papillomas.[7][10] Typically performed using a laryngeal endoscopy, surgery can protect intact tissues and the individual's voice, as well as ensure that the airway remains unobstructed by the disease.[2] However, surgery does not prevent recurrences, and can lead to a number of serious complications.[9][7][10] Laser technology, and carbon dioxide laser surgery in particular, has been used since the 1970s for the removal of papillomas; however, laser surgery is not without its risks, and has been associated with a higher occurrence of respiratory tract burns, stenosis, severe laryngeal scarring, and tracheoesophagyeal fistulae.[9][2][7][10] Tracheotomies are offered for the most aggressive cases, where multiple debulking surgery failures have led to airways being compromised.[2][7] The tracheotomies use breathing tubes to reroute air around the affected area, thereby restoring the person's breathing function. Although this intervention is usually temporary, some people must use the tube indefinitely.[8] This method should be avoided if at all possible, since the breathing tube may serve as a conduit for spread of the disease as far down as the tracheobronchial tree.[2][7]

A microdebrider is a tool that can suction tissue into a blade, which then cuts the tissue. Microdebriders are gradually replacing laser technology as the treatment of choice for laryngeal papillomatosis, due to their ability to selectively suction papillomas while relatively sparing unaffected tissue.[2][10] In addition to the lower risk of complications, microdebrider surgery also is reportedly less expensive, less time-consuming, and more likely to give the person a better voice quality than the traditional laser surgery approaches.[10]

Nonsurgical adjuvant treatment[edit]

For about 20% of people, surgery is not sufficient to control their laryngeal papillomatosis, and additional nonsurgical and/or medical treatments are necessary.[7] As of 2015, these treatments alone are not sufficient to cure laryngeal papillomatosis, and can only be considered supplemental to surgery.[2] Some varieties of nonsurgical treatments include interferon, antiviral drugs (especially cidofovir, but also ribavirin and acyclovir), and photodynamic therapy.[9][2][7][10][12] The monoclonal antibody against vascular endothelial growth factor (VEGF), bevacizumab, has shown promising result as an adjuvant therapy in the management of recurrent respiratory papillomatosis.[20][21]

Although vaccines are normally used to prevent infections from happening, HPV vaccines can be used therapeutically (after the infection has occurred).[22][23] For most patients, the HPV vaccine significantly increases the length of time needed between surgeries.[19][22][23]

Prognosis[edit]

The evolution of laryngeal papillomatosis is highly unpredictable and is characterized by modulation of its severity and variable rate of progression across individuals.[4][1] While instances of total recovery are observed, the condition is often persistent and lesions can reappear even after treatment.[8][1][11] Factors that might affect the clinical course of the condition include: the HPV genotype, the age at onset, the elapsed time between the diagnosis and first treatment in addition to previous medical procedures.[7][17][1] Other factors, albeit controversial, such as smoking or the presence of gastroesophageal reflux disease might also play a role in the progression of the disease.[17][3]

The papillomas can travel past the larynx and infect extralaryngeal sites.[4] In more aggressive cases, infection of the lungs can occur with progressive airway obstruction.[4][5] Although rare (less than 1% of people with laryngeal papillomatosis), transformation from a benign form to a malignant form is also observed.[4][5] Death can result from these complications (morbidity rate is around 1–2%).[4]

Epidemiology[edit]

Laryngeal papillomatosis is a rare disease with a bimodal distribution based on age of incidence.[1] The incidence, or number of new cases, of laryngeal papillomatosis cases is at approximately 4.3 cases per 100,000 children and 1.8 cases per 100,000 adults annually.[7][6][12][1] The incidence of laryngeal papillomatosis in children peaks before the age of 5, though the term juvenile papillomatosis refers to all cases occurring before the age of 20.[1][7] The incidence of adult laryngeal papillomatosis, which has an onset after the age of 20, peaks between the ages of 20 and 40.[7][1] While there are no gender differences in the incidence of laryngeal papillomatosis in children, adult laryngeal papillomatosis occurs more frequently in males than in females.[7][17][1] The incidence of laryngeal papillomatosis also varies according to factors such as socioeconomic status, such that higher rates are observed in groups having a lower socioeconomic status.[7]

Costs[edit]

Because of its relative commonness and the cost of treatments, more money is spent on treating RRP than on any other benign airway tumor.[22]

Research[edit]

As of 2015, use of the measles–mumps–rubella vaccine to reduce rate of recurrences had been investigated, but had not yielded significant results.[2]

See also[edit]

References[edit]

  1. ^ a b c d e f g h i j k l m n o p El-Naggar AK, Chan JK, Grandis JR, Takashi T, Slootweg PJ, eds. (2017). "Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space". World Health Organization Classification of Head and Neck Tumours. Lyon: International Agency for Research on Cancer. pp. 93–95. ISBN 9789283224389. OCLC 990147303.
  2. ^ a b c d e f g h i j k l Carifi M, Napolitano D, Morandi M, Dall'Olio D (2015). "Recurrent respiratory papillomatosis: current and future perspectives". Therapeutics and Clinical Risk Management. 11: 731–738. doi:10.2147/TCRM.S81825. PMC 4427257. PMID 25999724.
  3. ^ a b c Taliercio S, Cespedes M, Born H, Ruiz R, Roof S, Amin MR, Branski RC (January 2015). "Adult-onset recurrent respiratory papillomatosis: a review of disease pathogenesis and implications for patient counseling". JAMA Otolaryngology–Head & Neck Surgery. 141 (1): 78–83. doi:10.1001/jamaoto.2014.2826. PMID 25393901.
  4. ^ a b c d e f g h i j Mehta AC, Jain P, Prasoon G, Gildea TR (2016). Diseases of the central airways : a clinical guide. Springer. pp. 215–218. ISBN 9783319298283. OCLC 945577007.
  5. ^ a b c d e f g Venkatesan NN, Pine HS, Underbrink MP (June 2012). "Recurrent respiratory papillomatosis". Otolaryngologic Clinics of North America. 45 (3): 671–694, viii–ix. doi:10.1016/j.otc.2012.03.006. PMC 3682415. PMID 22588043.
  6. ^ a b c d e f g Grimes J, Fagerberg K, Smith L, eds. (2014). "Laryngeal Papillomatosis". Sexually Transmitted Disease : An Encyclopedia of Diseases, Prevention, Treatment, and Issues. Greenwood. pp. 401–403. ISBN 9781440801341. OCLC 880530919.
  7. ^ a b c d e f g h i j k l m n o p q r s t u v w x y Fortes HR, von Ranke FM, Escuissato DL, Araujo Neto CA, Zanetti G, Hochhegger B, et al. (May 2017). "Recurrent respiratory papillomatosis: A state-of-the-art review". Respiratory Medicine. 126: 116–121. doi:10.1016/j.rmed.2017.03.030. hdl:10923/22484. PMID 28427542.
  8. ^ a b c d e f g "Recurrent Respiratory Papillomatosis or Laryngeal Papillomatosis". NIDCD. 2015-08-18. Retrieved 2017-10-21.
  9. ^ a b c d e f g Alfano DM (2014). "Human papillomavirus laryngeal tracheal papillomatosis". Journal of Pediatric Health Care. 28 (5): 451–455. doi:10.1016/j.pedhc.2014.04.003. PMID 24882788.
  10. ^ a b c d e f g h i Avelino MA, Zaiden TC, Gomes RO (September 2013). "Surgical treatment and adjuvant therapies of recurrent respiratory papillomatosis". Brazilian Journal of Otorhinolaryngology. 79 (5): 636–642. doi:10.5935/1808-8694.20130114. PMC 9442437. PMID 24141682.
  11. ^ a b Drejet S, Halum S, Brigger M, Skopelja E, Parker NP (March 2017). "A Systematic Review". Otolaryngology–Head and Neck Surgery. 156 (3): 435–441. doi:10.1177/0194599816683384. PMID 28072562. S2CID 4406970.
  12. ^ a b c d e f g h Colton RH, Casper JK, Leonard R (2011). Understanding Voice Problems : A Physiological Perspective for Diagnosis and Treatment (4th ed.). Philadelphia, PA: Lippincott Williams & Wilkins. pp. 171–172, 224–228. ISBN 9781609138745. OCLC 660546194.
  13. ^ a b c d e f g Larson DA, Derkay CS (June 2010). "Epidemiology of recurrent respiratory papillomatosis". APMIS. 118 (6–7): 450–454. doi:10.1111/j.1600-0463.2010.02619.x. PMID 20553527. S2CID 193686.
  14. ^ a b c d e f g Barnes L (2005). Pathology and genetics of head and neck tumours (PDF). IARC Press Lyon. pp. 144–145.
  15. ^ Derkay CS, Wiatrak B (July 2008). "Recurrent respiratory papillomatosis: a review". The Laryngoscope. 118 (7): 1236–1247. doi:10.1097/MLG.0b013e31816a7135. PMID 18496162. S2CID 12467098.
  16. ^ Niyibizi J, Rodier C, Wassef M, Trottier H (February 2014). "Risk factors for the development and severity of juvenile-onset recurrent respiratory papillomatosis: a systematic review". International Journal of Pediatric Otorhinolaryngology. 78 (2): 186–197. doi:10.1016/j.ijporl.2013.11.036. PMID 24367938.
  17. ^ a b c d e f g Wenig BM, Fletcher CD (2013). "Tumors of the Upper Respiratory Tract". In Fletcher CD (ed.). Diagnostic Histopathology of Tumors (4th ed.). Philadelphia, PA: Saunders/Elsevier. pp. 92–98. ISBN 9781455737543. OCLC 846903109.
  18. ^ a b Grant DG, Mirchall MA, Bradley PJ (2010). "Surgery for Benign Tumors of the Adult Larynx". In Remacle M, Eckel HE (eds.). Surgery of Larynx and Trachea. Berlin: Springer-Verlag Berlin Heidelberg. pp. 91–112. ISBN 9783540791355. OCLC 567327912.
  19. ^ a b Ivancic R, Iqbal H, deSilva B, Pan Q, Matrka L (February 2018). "Current and future management of recurrent respiratory papillomatosis". Laryngoscope Investigative Otolaryngology. 3 (1): 22–34. doi:10.1002/lio2.132. PMC 5824106. PMID 29492465.
  20. ^ Mohr M, Schliemann C, Biermann C, Schmidt L-H, Kessler T, Schmidt J, et al. Rapid response to systemic bevacizumab therapy in recurrent respiratory papillomatosis. Oncol Lett. 2014 Nov;8(5):1912–8.
  21. ^ Sidell DR, Nassar M, Cotton RT, Zeitels SM, de Alarcon A. High-dose sublesional bevacizumab (avastin) for pediatric recurrent respiratory papillomatosis. Ann Otol Rhinol Laryngol. 2014 Mar;123(3):214–21.
  22. ^ a b c Derkay CS, Bluher AE (December 2018). "Recurrent respiratory papillomatosis: update 2018". Current Opinion in Otolaryngology & Head and Neck Surgery. 26 (6): 421–425. doi:10.1097/MOO.0000000000000490. PMID 30300210. S2CID 52947478.
  23. ^ a b Pham CT, Juhasz M, Sung CT, Mesinkovska NA (January 2020). "The human papillomavirus vaccine as a treatment for human papillomavirus-related dysplastic and neoplastic conditions: A literature review". Journal of the American Academy of Dermatology. 82 (1): 202–212. doi:10.1016/j.jaad.2019.04.067. PMID 31085272. S2CID 155092723.

External links[edit]

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