Outcomes After Human Papillomavirus Vaccination in Patients With Recurrent Respiratory Papillomatosis

Abstract

IMPORTANCE Recurrent respiratory papillomatosis (RRP) is a rare benign chronic disease of the larynx etiologically linked with the infection of low-risk human papillomavirus (HPV). Combination of surgical and immunomodulatory therapy has limited success. Possible use of prophylactic HPV vaccine that includes HPV-6 and HPV-11 antigens has been studied. OBJECTIVE To evaluate if the HPV vaccination is associated with a lower number of recurrences requiring surgical intervention in patients with new and recurrent RRP. DESIGN, SETTING, AND PARTICIPANTSThis was a non-placebo-controlled intervention study. Enrollment data were collected from October 2011 to August 2013. The patients were followed up at 1 month, 12 months, and 5 years after the third dose of the vaccine and clinically monitored until December 31, 2018. Data were analyzed from 2019 to 2021. Altogether, 50 adults with active RRP were enrolled and followed up in referral centers. For the final outcome, follow-up data for 42 patients were available. Eight patients who did not fulfill the protocol were excluded.INTERVENTIONS All patients received HPV vaccine as an adjuvant treatment and were clinically followed up. When RRP progression or a significant recurrent lesion was detected, surgical removal via direct laryngoscopy was indicated. No adjuvant therapy with antiviral or biological agents was used. MAIN OUTCOMES AND MEASURESThis study compared the prevaccination and postvaccination positivity for HPV-specific antibodies. The main outcome was the difference in the frequency of RRP recurrences in the prevaccination and postvaccination period.RESULTS A total of 50 patients with RRP were enrolled (median [SD] age, 41.5 [12.3] years [range,; 39 [78%] men and 11 [22%] women). After HPV vaccination, patients with previously no HPV-specific antibodies showed seroconversion, and all patients developed 100-fold higher levels of HPV vaccine type-specific antibodies compared with the prevaccination period. In patients with recurrent RRP, decreased frequency of recurrences requiring surgical treatment was present after vaccination (from 0.85 to 0.36 recurrences/y). No difference in postvaccination recurrences was found between patients with newly diagnosed and recurrent RRP. CONCLUSIONS AND RELEVANCEIn this nonrandomized clinical trial, the frequency of RRP recurrences was significantly lower after HPV vaccination, and patients with RRP thus had a reduced burden of disease. Because no difference was detected in the frequency of recurrent postvaccination lesions in patients with new and recurrent disease, it appears that both groups showed equal benefit following HPV vaccination. These findings suggest that the earlier that patients with RRP receive HPV vaccine, the sooner they may show reduced burden of disease.

Impact of HPV vaccination on number of surgical procedures required in recurrent respiratory papillomatosis and its potential use as an adjuvant

“…13 More recently a 2022 non placebo controlled intervention study by Smahelova et al compared recurrencies in prevaccination and postvaccination period of 42 patients. 14 In this non randomised trial, the frequency of recurrences requiring surgical treatment was significantly lower after vaccination (from 0.85 to 0.36 recurrences yearly). No difference in postvaccination recurrences was found between patients with newly diagnosed and recurrent RRP.…”

Recurrent Respiratory Papillomatosis (RRP) – Meta-analyses on the use of the HPV vaccine as adjuvant therapy.

“…Mauz et al 2018 26 and Matsuzaki et al 2019 27 were then excluded due to the lack of pre-immunisation data which was required for analyses. Personal communications with Smahelova et al 2022 24 allowed us access to unpublished and just published data and has helped to reduce bias. See Fig.…”

“…We have also searched through ClinicalTrials.gov for studies which were not included in the Rosenberg metaanalyses. We found one study for which no published data was available at the time (now just published), and we contacted the authors who kindly provided their data(Smahelova et al 2022 24 -NCT01375868).…”

Association between human papillomavirus particle production and the severity of recurrent respiratory papillomatosis

“…These findings suggest that persistent production of HPV particles, resulting in persistent infection, is the main pathogenesis of RRP. The combination of surgery and HPV vaccination has www.nature.com/scientificreports/ been reported to reduce the risk of recurrence 30,31 . These reports support this hypothesis.…”