Papilloma are benign ‘warts’ growing mostly in the larynx on the vocal folds (syn. vocal cords). They are caused by viruses called human papilloma virus – HPV. Papilloma grow on vocal folds, but also on other sites of the larynx. Although many people are infected by HPV, only very few people have papilloma within the larynx. Some studies say that more than 10 % of the population are infected, but only approx. 3 out of 100,000 people suffer from papillomatosis. The reason for this is not clear. Because small children and adults can show first symptoms at various ages, clinicians divide RRP in the two groups: the juvenile onset and adlut onset group. One of the biggest problems in RRP is that papilloma tend to continue to grow, reducing airway space and causing respiratory problems that can be severe to life-threatening.
There are many HPV subtypes (HPV-DNA) causing laryngeal papilloma. However, by far most frequent are the types 6 and 11. Those are called ‘low-risk’ types because very rarely they develop malignant disease. Other types are associated with higher transformation rates for malignancy (‘high-risk’ types).
Due to the most frequent localisation of papilloma on human vocal folds, the disease can be detected early by audible affection of the voice – hoarseness is therefore an early sign of disease. Unfortunately, the disturbed voice has no characteristic sound, and therefore an endoscopy of the larynx is mandatory for diagnosis, followed by a biopsy confirming the histology of the papilloma. Children with their small airways may run into airway problems early in disease. The lower airways (trachea, lungs) and the oral and nasal cavity can also be affected. Thus, airway endocopy to rule out RRP is obligatory.
With high resolution small flexible endoscopes the diagnosis can be made with a very high degree of certainty in office-based transnasal, painless endoscopy – even in neonates. With our tip-chip high resolution endoscopes with NBI (narrow-band imaging) spectral light filter technology we can rule out – or ascertain – the diagnosis of RRP of the larynx.
When RRP is suspected, we would strongly recommend a biopsy for histological verification of the diagnosis including virus typing (HPV-DNA type 6, 11, or other type) as a next step. This is mostly combined with a reduction of papilloma masses to improve voice and / or breathing. It cannot be stated often enough that surgical treatment of RRP is not a radical technique, since papilloma tend to recur and a radical surgical approach would lead to scarring, which itself causes hoarseness. Because surgery is significant mass reduction (debulking), the clinical treatment of RRP needs additional measures.
An additional treatment for RRP is the photoangiolytic approach to reduce papilloma masses. With a special laser, the vessels inside of the papilloma are selectively coagulated and dried out with a KTP or blue laser. This laser treatment can be applied in adults in the office – a painless treatment in an office surgical setting. However, children cannot receive this office-based laser treatment because of their – mostly not so compliant – behaviour. With photoangiolytic laser treatment patients can avoid surgery in general anesthesia. In the USA, many patients with RRP receive photoangiolytic laser treatment.
We strongly recommend vaccination with a vaccine that addresses the HPV-DNA subtype of the patient. Although not evidence-based in its effect and ‘off-label’ as a pharmaceutical agent for the treatment of papilloma, there are some studies that suggest a positive effect on slowing down the progression rate of the papilloma after vaccination.
Since twenty years, many colleagues have made positive experiences with intralesional (=into the papilloma) Cidofovir injections. Although Cidofovir is not evidence-based in its effect and ‚off-label’ as a pharmaceutical agent for the treatment of papilloma, there are multiple studies that suggest that Cidofovir has a positive effect on slowing down the progression rate of the papilloma after repetitive administration intralesionally. Since we use it in a cyclical manner every 6 weeks, we can state that more than 90 % of our patients had good to very good response rates – and some patients are now in complete remission (no visual papilloma in high magnification endoscopy). Also, we have not encountered any side effect of Cidofovir so far.
After treating more than 20 patients with RRP, we recommend a multimodal approach