Papillomatosis is the growth of multiple papillomas, which are benign (noncancerous) tumors that form on the surface of skin or mucous membranes and typically grow outward. These growths can appear in the throat, on the skin, or on internal organs, and the term covers several distinct conditions depending on where they develop and what causes them. The most clinically significant forms are recurrent respiratory papillomatosis, which affects the airway, and confluent and reticulated papillomatosis, a skin condition seen mostly in teenagers and young adults.
Types of Papillomatosis
The word “papillomatosis” simply describes a pattern of multiple papilloma growths, but in practice it refers to a few specific conditions that behave very differently from one another.
Recurrent respiratory papillomatosis (RRP) involves wart-like growths in the larynx (voice box) and upper airway, caused by the human papillomavirus (HPV). It can affect both children and adults and often requires repeated treatment over many years.
Confluent and reticulated papillomatosis (CARP) is a skin condition that produces dark, slightly raised patches on the upper trunk and neck. It is not caused by HPV and is instead linked to abnormal skin cell turnover.
Cutaneous papillomas are the most familiar form: common skin tags. These small, flesh-colored growths are harmless and extremely common, especially in areas where skin folds or rubs together.
Recurrent Respiratory Papillomatosis
RRP is the most serious form of papillomatosis. It causes clusters of wart-like growths on the vocal cords and surrounding airway tissue, leading to a progressively hoarse voice, breathing difficulties, and in children, a weak cry or stridor (a high-pitched breathing sound). The condition is estimated to affect about 4.3 per 100,000 children and 1.8 per 100,000 adults in the United States, with roughly equal numbers of males and females.
The vast majority of cases are caused by HPV types 6 and 11, though rarer strains (types 16, 18, 31, and 33) can also be responsible. Children typically acquire the virus during birth from a mother with an active HPV infection. The average age at diagnosis for the juvenile-onset form is 5 years old, while adult-onset cases are usually diagnosed around age 37.
What makes RRP especially burdensome is the word “recurrent.” The growths tend to come back after removal, sometimes requiring dozens of surgeries over a lifetime. Until recently, management consisted almost entirely of repeated surgical procedures, which address the growths but not the underlying viral cause.
Malignant Transformation Risk
Although papillomas are benign, a small percentage of RRP cases can progress to squamous cell carcinoma. Overall, malignant transformation occurs in roughly 0.5% of patients with RRP. The risk jumps considerably when the disease spreads to the lungs, which happens in about 3.3% of RRP patients. Among those with pulmonary involvement, cancer develops in approximately 16%, making lung spread an important red flag for closer monitoring.
How RRP Is Treated
Surgery remains the primary treatment. The goal is to remove all visible papillomas while preserving healthy tissue and minimizing scarring, which is especially important near the vocal cords. Three main surgical approaches are used: cold instrument surgery, laser surgery, and microdebrider surgery. In recent years, the microdebrider has become the preferred tool for many surgeons because it offers shorter operating times, lower complication rates, better voice outcomes, and lower cost compared to laser-based procedures. Laser surgery carries a somewhat higher risk of airway scarring and other complications.
For patients who need frequent surgeries, additional therapies may be used alongside procedures to slow regrowth. These include antiviral medications injected directly into the growths and immune-boosting treatments. The antiviral cidofovir has been widely studied as an add-on therapy, though results have been mixed, with some studies showing benefit and others finding little improvement.
A significant development came when the FDA granted full approval to a new immunotherapy called pembrolizumab (brand name Papzimeos), the first non-surgical treatment specifically approved for adult RRP. This treatment uses a modified virus to stimulate the immune system to target and clear HPV-infected cells, addressing the root cause of the disease rather than just removing growths as they appear.
HPV Vaccination Has Reduced RRP Dramatically
The HPV vaccine, originally developed to prevent cervical cancer, has had a striking effect on RRP rates. Australia, which achieved vaccination rates above 80% in girls and above 75% in boys, saw the incidence of childhood RRP plummet from 0.16 to 0.02 per 100,000 children. By 2019, no new pediatric cases were reported across the entire country. Preliminary data from a CDC-funded study in the United States shows a similar decline in RRP incidence between the pre-vaccination era (2004 to 2005) and the post-vaccination era (2012 to 2013). Because the most common RRP-causing strains, HPV 6 and 11, are included in the standard HPV vaccine, widespread vaccination has the potential to nearly eliminate juvenile-onset RRP.
Confluent and Reticulated Papillomatosis
CARP is an entirely different condition from RRP. It shows up as small (about 5 mm) brown or darkly pigmented spots and bumps, primarily on the upper back, chest, and neck. In the center of affected areas, the spots merge together into larger patches, while around the edges they form a lace-like or net-like (reticulated) pattern. The skin in these areas may feel slightly velvety, scaly, or warty. The condition is painless and not itchy, but it can be cosmetically distressing.
CARP most commonly appears in teenagers and young adults. A study at the Mayo Clinic found a mean age of 15 at diagnosis, while studies in Japan and Singapore reported average onset ages of 17 and 29, respectively. Males are affected slightly more often than females. It occurs more frequently in Caucasian populations.
The exact cause remains debated. A fungus called Malassezia furfur was once considered the culprit, but many patients with CARP show no evidence of this organism. The leading current theory points to a bacterium called Dietzia papillomatosis. Other contributing factors may include diabetes, obesity, ultraviolet light exposure, and genetic variations in how skin cells produce keratin.
Diagnosis and Treatment of CARP
CARP can be mistaken for a fungal skin infection because of its appearance, but it does not respond to antifungal creams or pills. In fact, failure to improve with antifungal treatment is one of the diagnostic criteria. A proper diagnosis typically involves confirming the characteristic appearance on the upper trunk and neck, ruling out fungal infection through skin scraping tests, and observing a strong response to antibiotic therapy.
The standard treatment is an antibiotic from the tetracycline family, most often minocycline. Doses typically range from 50 to 200 mg daily for three weeks to three months, sometimes combined with a topical retinoid cream applied at bedtime. Some patients see complete clearance in as little as three weeks with this combination. The condition does tend to recur after antibiotics are stopped, so some people need longer courses or tapering schedules to maintain results. Other treatment options include azithromycin, isotretinoin, and various topical medications, though minocycline remains the first choice for most dermatologists.
How Papillomatosis Is Diagnosed
The diagnostic approach depends on the type. For RRP, an ear, nose, and throat specialist examines the airway using a small camera (laryngoscopy) and takes a tissue sample for biopsy. Under a microscope, papillomas show characteristic features: thickened surface layers, finger-like projections of tissue, and distinctive cells called koilocytes, which have a clear halo around the nucleus and are a hallmark sign of HPV infection. HPV testing on the tissue sample can confirm the specific viral strain involved.
For CARP, diagnosis is primarily clinical, based on the appearance and location of the rash combined with its response to treatment. A skin biopsy can support the diagnosis by showing thickened outer skin layers and the papillomatosis pattern, but it is not always necessary if the clinical picture is clear.