• Sign Up

Papilloma


Papilloma

Article Author:
Ahmed Sabry
Article Editor:
Bhupendra Patel
Updated:
7/18/2020 12:14:46 PM
For CME on this topic:
Papilloma CME
PubMed Link:
Papilloma

Introduction

A papilloma is a benign (non-cancerous) tumor arising from an epithelial surface and usually known to grow in an outward direction. Commonly, a papilloma refers to squamous cell papillomas which appear as frond-like tumors that can develop almost anywhere on the body with squamous epithelium:

  • Skin: as warts and cutaneous papillomas
  • Lip
  • Oral cavity
  • Eyelid
  • Tongue
  • Pharynx
  • Larynx
  • Esophagus
  • Cervix
  • Genital tract: known as genital warts

Most of these lesions are caused by Human Papillomavirus (HPV). They are contagious upon contact with the exception of cutaneous papilloma, which is also called an acrochordon or more commonly known as a skin tag. Most of these lesions are usually self-limiting in immunocompetent individuals.[1]

Etiology

The majority of papillomas are caused by human papillomavirus (HPV). There are over 170 subtypes of the virus. Usually, types 6, 7, and 11 are mostly associated with papillomas and are called low-risk types as they don't usually cause precancerous lesions and rarely progress into cancer. HPV has been found to cause papillomas to arise almost anywhere in the body with stratified squamous epithelium, like the skin, conjunctiva, oropharynx, larynx and upper trachea as well as the anogenital tracts.[2]

Studies conducted have found HPV6/11 in 96% to 100% of all Genital wart lesions.[3][4] Infection is very contagious through direct and sexual contact. Genital HPV is spread by sustained direct skin-to-skin contact. Vaginal, anal, or oral sex are the most common ways of spread. Several studies conducted have shown that most skin tags or cutaneous papillomas of the head and neck to be non-contagious, unlike warts despite containing low-risk forms of HPV DNA, especially of type 6/11.[5][6][7] However, a study conducted by Pezeshkpoor et al. had found no significant association between skin tags and HPV.[8] This is why we term non-viral growths as acrochordons.

There is evidence of vertical transmission of human papillomavirus from mothers to their infants.[9] This may lead to the development of several papillomas in the larynx and upper trachea called Recurrent Respiratory Papillomatosis. It is a serious condition, as the papillomas may eventually enlarge causing obstruction of the airway.

It is worth noting that some papillomas are non-viral in origin as in the inverted papilloma of the urinary tract which has strongly been associated with smoking.[10] Nasal papillomas may be caused by local irritation and trauma to the mucosa, and some cutaneous papillomas have been associated with skin irritation. An example of this was cutaneous papillomas that had occurred in rats, mice, and hamsters following the local application of powerful carcinogens where they are believed to arise from the stratified squamous epithelium.[11] In addition, there are types of papillomas in which the mechanism responsible for their occurrence isn't fully understood, as in intraductal (breast duct) papillomas and choroid plexus papillomas.

Epidemiology

The global prevalence of HPV infection, the main cause of papillomas, is around 11% to 12%. However, reliable surveillance figures are difficult to obtain regarding the prevalence of warty lesions. For non-genital warts, two large population-based studies found prevalence rates of 0.84% in the US and 12.9% in Russia, with prevalence being highest in children and young adults.[12] For genital warts, the annual incidence was found to be between 0.1 to 0.2% of the population in developed countries. The highest prevalence was found amongst teens and young adults.

Acrochorda or skin tags have been reported to have a prevalence of 46% in the general population with a higher prevalence among older age groups, unlike warty papillomas. They are more common in the obese and tend to grow in areas of skin-to-skin contact. They have an equal distribution among males and females.

Pathophysiology

Papillomas arise from the skin or some mucosal surfaces depending on the different types of Human Papillomavirus involved and their affinity to different sites. For example, conjunctival papilloma is caused by HPV infection type 6, 11, 16, 33, and 45, which is somewhat dissimilar to genital warts caused by types 2, 3, 6, 11, 16, 18, and 30-32 and cutaneous papillomas (types 1-4 and 26-29).

Infection is established in the basal cell layers of the epithelium, but this involves the expression of a limited part of the viral genome. It's not until the basal cells develop and move externally through the different layers of the skin of the stratum spinosum and granulosum, that the virus begins to replicate itself, and the lesion becomes infectious.

Normally papillomavirus infects the epidermis in sites near the site of entry, but self inoculation often occurs, and the virus can infect farther sites. This phenomenon is known as the Koebner phenomenon. It has been observed that the immune system has an important role in controlling the spread of the virus, as, despite the virus infecting the intraepidermal cells that are considered "hard-to-reach" by the immune system, it was found that papillomas tend to reactivate and are more extensive in immunocompromised individuals.

Histopathology

Papillomas take origin from an epithelial surface. Complex folds of proliferating epithelium can be observed and are accompanied by a growth of supporting connective tissue and blood vessels. Typical examples are found in the skin, e.g., the common wart. Under the light microscope, these benign tumors show: 

  • Normally arranged epithelial cells e.g., in skin papillomas, the surface cells are squamous, and proliferation is confined to the deepest layers. 
  • The inner layer is a fibrovascular core with well-formed blood vessels.
  • The outer layer is the epithelium, which is infolded and characterized by acanthosis, papillomatosis, and hyperkeratosis.
  • The relationship of the epithelium to connective tissue is normal. They show no evidence of infiltration or invasion of the underlying connective tissues.
  • In the case of conjunctival papillomas, pedunculated papillomas are usually covered by conjunctival epithelium.

History and Physical

History

  • The patient usually complains of a small rough bump arising from the skin. This may either be painless or painful.
  • The patient may describe habits that increase the risk factor for transmission, such as showering in communal showers, professionally handling meat products, and farm animals bare-handed or performing unsafe sex.
  • The patient may report other symptoms that are more specific with the site from where the papilloma arises.
  • Intraductal papillomas arising from the breast may present with bloody nipple discharge.
  • Recurrent respiratory papilloma arising from the larynx and trachea may cause stridor and voice hoarseness.
  • Nasal Papillomas can cause sinusitis and the loss of smell[13]

Physical Findings

Single or multiple solid papules are observed. On the skin, it may appear as a rough solid papule, often covered with hyperkeratinized skin. Those arising on mucosal surfaces appear as a soft, pedunculated mass (supported on a stem or stalk) with numerous finger-like projections. The projections may be long and pointy or short and rounded if keratin has built-up around the lesion. Less keratinized lesions are pink or red in color and resemble a raspberry, whilst heavily keratinized lesions are white and look like the head of cauliflower.

Evaluation

Usually, most squamous cell papillomas are diagnosed upon examination and require no further investigations, especially in immunocompetent individuals where they are self-limiting and don't transform to malignant lesions. However, in those considered to have a higher risk of turning malignant, e.g: anogenital and oropharyngeal tract papillomas, they may undergo excision and a biopsy is sent for histopathological investigations if there is any question as to the diagnosis or if there is a concern for dysplasia.[14][15]

Although genital warts are usually caused by low-risk HPV subtypes, 5% to 20% of the individuals affected have been found to carry other sexually transmitted diseases. It is always important to suspect high-risk HPV infections that cause precancerous lesions in those individuals with genital warts and early screening should be initiated. Screening for cervical dysplasia/malignancy is typically accomplished through speculum examination and Pap smear.

Treatment / Management

Sometimes painless cutaneous papillomas may be left untreated and regress with time. They seem to not increase in size over time, and the potential for malignant transformation is low in immunocompetent individuals. If treatment is indicated, it varies depending on the type, size, and location of the papilloma.

  • Skin warts and genital warts are managed with topical medications or procedures, such as cryotherapy or laser surgery.
  • Skin warts may also be removed by excision (whether cutting it with a scalpel or cauterizing it).
  • Surgical removal is a primary treatment for papillomas of the brain, breast ducts, and respiratory tract.
  • Papillomas tend to recur around the primary site of infection, and the need for retreatment may be required.
  • No-touch techniques of surgical removal with cryotherapy have been found to help prevent viral dissemination and reduce the papilloma recurrence.[16]

Differential Diagnosis

There is a wide range of diseases characterized by an overgrowth of the epithelial tissue giving solid papules on the skin that have to be differentiated from papillomas. 

  • Acrochordon
  • Adenoma
  • Basal cell carcinoma
  • Chancroid
  • Condyloma latum
  • Corns & calluses
  • Cysts
  • Emilia
  • Herpes simplex
  • Keratoacanthoma
  • Molluscum contagiosum: caused by a poxvirus and forms fleshy papules.
  • Psoriasis
  • Moles
  • Neurofibromas
  • Nevus lipomatosus
  • Seborrheic keratoses

Prognosis

The prognosis of papillomas caused by HPV infection is usually good in immunocompetent individuals, but recurrences may occur. Some subtypes of HPV may cause vulvar intraepithelial dysplasia, cervical dysplasia, and cervical cancer. Although these subtypes don't typically cause papillomas, they are commonly present side by side with genital papillomas.

In immunocompromised individuals, papillomas often increase and spread more rapidly, and there is a higher risk of papillomas transforming into malignancy.[17]

Complications

Rarely are papillomas able to cause serious and life-threatening complications. This mainly depends on the anatomical site of the lesion.

  • Recurrent respiratory papillomatosis may grow extensively and rapidly in the larynx and upper trachea, causing upper airway obstruction and stridor.
  • Choroid plexus papillomas in the brain cause increased cerebrospinal fluid production and can lead to increased intracranial pressure and hydrocephalus, which may eventually lead to brain herniation and death. 
  • Papillomas in themselves are rarely premalignant in immunocompetent individuals; however, malignant transformation still does occur.
  • A papilloma at the lacrimal punctum may grow into the punctum and canaliculus and involve the lacrimal sac and nasolacrimal duct (inverted papilloma).

Deterrence and Patient Education

Here are important points to take care of to prevent papilloma:

  • Safe sex
  • Routine Pap smear screen
  • Wearing flip-flops while taking communal showers
  • Taking caution upon the occupational handling of meat and preferably wear disposable gloves
  • Warts are usually contagious upon direct contact. Skin tags, however, are not contagious
  • Vaccination: HPV vaccine is available and recommended to be taken by ages 9-12 to prevent certain precancerous lesions in males and females. The 9 valent vaccine is effective against Human Papillomavirus subtypes 6,11,16,18,31,33,45,52 and 58.

Enhancing Healthcare Team Outcomes

HPV is the most common cause of papillomas of the mucous membranes and skin. There are over 175 subtypes of HPV, and some are associated with an increased risk of malignancy. 

For the most part, HPV is acquired by direct contact of other infected individuals or livestock, and one of the best ways to decrease the morbidity of this infection is through education.

Patient counseling by the pharmacist is important to educate individuals about the different treatments available for warts, their benefits, and adverse effects.

It is important to educate teens who are about to start being sexually active about safe sex by their school nurse or trained teachers.

Furthermore, it is necessary to let parents know the importance of vaccinating their children before being sexually active.

Encourage sexually active females with genital warts to undergo the pap smear to determine the presence of cervical dysplasia and high-risk HPV infections. Patients with genital warts should avoid sexual activity until their warts are treated.

Patients should avoid touching their warts to avoid self inoculation.



(Click Image to Enlarge)
Cutaneous horn or "cornu cutaneum": keratin becomes compacted and looks like a pillar or animal horn, hence the name
Cutaneous horn or "cornu cutaneum": keratin becomes compacted and looks like a pillar or animal horn, hence the name
Contributed by Professor Bhupendra C. K. Patel MD, FRCS

(Click Image to Enlarge)
Acrochordons: acrochordons or skin tags come in many different forms. They are often associated with aging and with obesity and will often occur on parts of the body where this is friction between skin folds. They may be skin colored or pigmented and may be dome-shaped or elevated (papillomatous) Human papilloma virus (HPV) causes common warts, the small, white, beige or brown skin growths that can appear almost anywhere on the body and on the...
Acrochordons: acrochordons or skin tags come in many different forms. They are often associated with aging and with obesity and will often occur on parts of the body where this is friction between skin folds. They may be skin colored or pigmented and may be dome-shaped or elevated (papillomatous) Human papilloma virus (HPV) causes common warts, the small, white, beige or brown skin growths that can appear almost anywhere on the body and on the...
Contributed by Professor Bhupendra C. K. Patel MD, FRCS

(Click Image to Enlarge)
Viral papilloma: caused by human papilloma virus. The growths tend to be pedunculated and irregular and may shed. On eyelids and eyelid margins, shedding may result in other lesions. They are usually skin-colored and if they grow near the lacrimal puncta, they can grow into the canaliculus and result in an inverted papilloma with growth down the nasolacrimal system
Viral papilloma: caused by human papilloma virus. The growths tend to be pedunculated and irregular and may shed. On eyelids and eyelid margins, shedding may result in other lesions. They are usually skin-colored and if they grow near the lacrimal puncta, they can grow into the canaliculus and result in an inverted papilloma with growth down the nasolacrimal system
Contributed by Professor Bhupendra C. K. Patel MD, FRCS

References

[1] Karani LW,Musyoki S,Orina R,Nyamache AK,Khayeka-Wandabwa C,Nyagaka B, Human papillomavirus genotype profiles and cytological grades interlinkages in coinfection with HIV. The Pan African medical journal. 2020     [PubMed PMID: 32537071]
[2] Theotoka D,Morkin MI,Galor A,Karp CL, Update on Diagnosis and Management of Conjunctival Papilloma. Eye and vision (London, England). 2019;     [PubMed PMID: 31236424]
[3] Ball SL,Winder DM,Vaughan K,Hanna N,Levy J,Sterling JC,Stanley MA,Goon PK, Analyses of human papillomavirus genotypes and viral loads in anogenital warts. Journal of medical virology. 2011 Aug;     [PubMed PMID: 21678438]
[4] Brown DR,Schroeder JM,Bryan JT,Stoler MH,Fife KH, Detection of multiple human papillomavirus types in Condylomata acuminata lesions from otherwise healthy and immunosuppressed patients. Journal of clinical microbiology. 1999 Oct;     [PubMed PMID: 10488198]
[5] Dianzani C,Calvieri S,Pierangeli A,Imperi M,Bucci M,Degener AM, The detection of human papillomavirus DNA in skin tags. The British journal of dermatology. 1998 Apr;     [PubMed PMID: 9640372]
[6] Donà MG,Pichi B,Rollo F,Gheit T,Laquintana V,Covello R,Pescarmona E,Spriano G,Pellini R,Giuliani M,Tommasino M,Benevolo M, Mucosal and cutaneous human papillomaviruses in head and neck squamous cell papillomas. Head     [PubMed PMID: 27618734]
[7] Gupta S,Aggarwal R,Gupta S,Arora SK, Human papillomavirus and skin tags: is there any association? Indian journal of dermatology, venereology and leprology. 2008 May-Jun;     [PubMed PMID: 18583787]
[8] Pezeshkpoor F,Jafarian AH,Ghazvini K,Yazdanpanah MJ,Sadeghian A,Esmaili H,Karrabi M,Rohani F,Joushan B, An association of human papillomaviruses low risk and high risk subtypes with skin tag. Iranian journal of basic medical sciences. 2012 May;     [PubMed PMID: 23493098]
[9] Smith EM,Parker MA,Rubenstein LM,Haugen TH,Hamsikova E,Turek LP, Evidence for vertical transmission of HPV from mothers to infants. Infectious diseases in obstetrics and gynecology. 2010;     [PubMed PMID: 20300545]
[10] Brown AL,Cohen RJ, Inverted papilloma of the urinary tract. BJU international. 2011 Apr;     [PubMed PMID: 21492372]
[11] Sanders JM,Bucher JR,Peckham JC,Kissling GE,Hejtmancik MR,Chhabra RS, Carcinogenesis studies of cresols in rats and mice. Toxicology. 2009 Mar 4;     [PubMed PMID: 19114085]
[12] Loo SK,Tang WY, Warts (non-genital). BMJ clinical evidence. 2009 Sep 24;     [PubMed PMID: 21726478]
[13] De Luca LM,Sly L,Jones CS,Chen LC, Effects of dietary retinoic acid on skin papilloma and carcinoma formation in female SENCAR mice. Carcinogenesis. 1993 Mar;     [PubMed PMID: 8453733]
[14] Nunes EM,Talpe-Nunes V,Sichero L, Epidemiology and biology of cutaneous human papillomavirus. Clinics (Sao Paulo, Brazil). 2018 Aug 20;     [PubMed PMID: 30133564]
[15] Heo I,Kwak HJ,Nah EH,Cho S,Kim S,Cho HI, Evaluation of the LC-1000 Flow Cytometry Screening System for Cervical Cancer Screening in Routine Health Checkups. Acta cytologica. 2018;     [PubMed PMID: 29843120]
[16] Huang YM,Huang YY,Yang HY,Tsai CC,Yu WK,Kao SC,Kau HC,Liu CJ, Conjunctival papilloma: Clinical features, outcome, and factors related to recurrence. Taiwan journal of ophthalmology. 2018 Jan-Mar;     [PubMed PMID: 29675344]
[17] Jung K,Narwal M,Min SY,Keam B,Kang H, Squamous cell carcinoma of head and neck: what internists should know. The Korean journal of internal medicine. 2020 Jul 14     [PubMed PMID: 32663913]