Robert C. Waters, M.D., Assistant Professor, MUSC
Human Papilloma Virus

Human Papilloma Virus (HPV) causes a number of diseases and is most commonly discussed in reference to sexually transmitted diseases. HPV infection has a substantial impact in ENT. It has multiple subtypes that are associated with diseases extending from completely benign to invasive carcinoma.

There are more than 150 subtypes of HPV. Seventy-five percent of HPV types are associated with the common wart, and 25% are associated with diseases in the mucosa of the nose, sinuses, oropharynx, larynx, and ano-genital region. HPV types are categorized as low risk and high risk. The most common types seen in ENT are 6, 11, 16 and 18. Types 6 and 11 are low risk for malignancy. Types 16 and 18 are high risk. High risk is associated with cytologic changes of dysplasia, pre-cancer and malignancy. Infection of types 6, 11, 16 and 18 are largely contracted by sexual contact. There are reports of HPV infection in monogamous relationships, and in individuals with no sexual activity. HPV infections are very common. Seventy-five percent of sexually active people ages 15 - 49 years have been infected at sometime. Most HPV infections are temporary and resolve with no long term consequences. Five - ten percent of cases with HPV infection persist with significant impact on quality of life.

Adult laryngeal squamous papillomas. 
Photos courtesy of Ashli O'Rourke, M.D.



Recurrent respiratory papillomas (RRP) have been associated with genital condyloma since the 1950's. RRP is second to nodules as benign laryngeal lesions in children. There are approximately 20,000 cases of RRP in the US. RRP types 6 and 11 are also the most common subtypes associated with ano-genital condyloma. Pediatric RRP is most commonly diagnosed between ages 2 - 4 years. Adult RRP is most commonly diagnosed between ages 20 - 30 years. RRP in children is a more persistant and aggressive disease than the adult form.

About twenty-five percent of RRP are type 6, 66% are type 11, and 14% percent type 6 and 11. Types 16 and 18 are rare in RRP. Cases with type 11 alone and in combination with type 6 have more severe disease,,longer illness, and require more surgical procedures than cases with type 6 alone. Malignant transformation to squamous cell carcinoma is more common in type 11.

Pediatric RRP has a 200 - 400% increased risk of occurrence if the mother has active HPV disease at the time of delivery. Exposure at delivery may not be the only factor, as HPV has been found in amniotic fluid. The American College of OB-GYN does not have a C-section indication based on the mother's HPV status.


Within the nasal fossa, papillary lesions occur commonly on the vestibular skin. These squamous papillomas are benign, usually HPV types 2, 4 and 6. Types 2 and 4 are associated with the common wart. Treatments for these include excision, cautery and cryotherapy with recurrence being common. Inverting papillomas are a distinct pathologic sino-nasal entity. HPV types seen with inverting papilloma are 6, 11, 16 and 18. Fungiform papilloma are exophytic in growth usually occurring on the septum. Schneiderian and Inverting papillomas are located on the lateral nasal wall and sinus mucosa. These are locally invasive with ability to destroy bone, extend intraorbital and intracranial. Inverting and Schneiderian papillomas have potential for squamous cell malignancy. HPV types 6 and 11 are noted to have less frequent recurrence. Types 16 and 18 are more likely to recur and have malignant transformation. Tissue typing may be of value as to prognosis and recurrence.


Tobacco and alcohol. For years these two substances alone or together were felt to be the primary risk factors for head and neck cancers. From 1965 to 2009 there was a 50% decrease in the percent of smoking adults. The number of smokers changed little, but with population increase the percentage dropped substantially. Alcohol consumption shows a less dramatic but significant decrease in percentage of people drinking alcohol, and a decrease in the amount of alcohol consumed. With these risk factors decreasing the rates of oral cancers have decreased over the last 30 years, but there is an increase in tonsil and base of tongue cancer. HPV was first observed in Oro-pharyngeal squamous cell cancer in the 1980's. Since that time, the research into HPV + Oro-pharyngeal cancer has exploded. Typing of HPV in oro-pharyngeal cancer is necessary as treatment plans have changed dramatically over time based on these results. Most of the tumors that are HPV positive contain HPV type 16 with oncogenes E6 and E7. The increase in HPV + cancers is felt to represent the increase in HPV Genital infection rates over the last 30 years.


HPV DNA has been detected in cholesteatomas in rates from 3 - 36 %. There is no substantial evidence for HPV as a factor for cholesteatoma formation.


Because of the extent of disease that may occur in ENT from HPV, immunization information is very important. Current CDC recommendation is for a series of three vaccinations over a six month period for males and females ages 11 - 12 years, and for males and females who have not completed this series ages 13 - 21 years. Vaccination may be given as early as age 9 years and as late as age 26 years.

Two vaccines are FDA approved. Gardisil is for males and females and immunizes for types 6, 11, 16 and 18. Ceravix is for females only and immunizes for HPV 16 and 18. The HPV vaccine is not a preventative of other sexually transmitted diseases. The HPV vaccine is not a treatment for existing HPV disease. Additional boosters may be needed in the future, as length of protection is not known. Vaccinations are 99% effective for prevention of disease from the specific subtypes.



Robert C. Waters, M.D.

Medical University of South Carolina 


American Cancer Society : Human Papilloma Virus ( HPV ), Cancer, HPV Testing, and HPV Vaccines
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International Journal of Pediatric Otorhinolaryngology 2006;70:1779-1803
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National Institute of Health, Recurrent respiratory papillomatosis or laryngeal papillomatosis. October 2010
National Institute of Health, Tracking alcohol consumption over time. December 2003
Thapa N, Diagnosis and treatment of sinonasal inverted papilloma.
Society of Otolaryngologist of Nepal. 2010, Vol. 1 Issue 1p. 30-33
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Last modified: June 15, 2016