Department of Genetics and Microbiology, Faculty of Science, BIOCEV, Charles University, Prague, Czech Republic.
Institute of Hematology and Blood Transfusion, National Reference Laboratory for Papillomaviruses and Polyomaviruses, Prague, Czech Republic.
JAMA Otolaryngol Head Neck Surg. 2022 Jul 1;148(7):654-661. doi: 10.1001/jamaoto.2022.1190.
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.
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 PARTICIPANTS: This 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.
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.
This 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.
A total of 50 patients with RRP were enrolled (median [SD] age, 41.5 [12.3] years [range, 21-73 years]; 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.
In 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.
EudraCT Identifier: 2011-002667-14; ClinicalTrials.gov Identifier: NCT01375868.
复发性呼吸道乳头瘤病（RRP）是一种罕见的喉部良性慢性疾病，病因与感染低危型人乳头瘤病毒（HPV）有关。手术和免疫调节治疗的联合应用效果有限。已对包括 HPV-6 和 HPV-11 抗原在内的预防性 HPV 疫苗的可能用途进行了研究。
评估 HPV 疫苗接种是否与新发病例和复发病例的 RRP 患者需要手术干预的复发次数减少相关。
设计、地点和参与者：这是一项非安慰剂对照干预研究。2011 年 10 月至 2013 年 8 月期间收集入组数据。患者在接种第三剂疫苗后 1 个月、12 个月和 5 年进行随访，并在 2018 年 12 月 31 日之前进行临床监测。数据分析于 2019 年至 2021 年进行。共有 50 名患有活动性 RRP 的成年人在转诊中心入组并接受随访。最终，42 名患者可提供随访数据。8 名未按方案进行的患者被排除。
所有患者均接受 HPV 疫苗作为辅助治疗，并进行临床随访。当 RRP 进展或出现明显复发性病变时，通过直接喉镜进行手术切除。未使用抗病毒或生物制剂进行辅助治疗。
本研究比较了 HPV 特异性抗体接种前后的阳性率。主要结局是接种前后 RRP 复发频率的差异。
共纳入 50 例 RRP 患者（中位数[SD]年龄，41.5[12.3]岁[范围，21-73 岁]；39 例[78%]为男性，11 例[22%]为女性）。接种 HPV 疫苗后，以前无 HPV 特异性抗体的患者出现了血清转化，所有患者产生的 HPV 疫苗型特异性抗体水平均比接种前提高了 100 倍。在复发性 RRP 患者中，接种后需要手术治疗的复发频率降低（从 0.85 次/年降至 0.36 次/年）。新发和复发性 RRP 患者接种后复发的差异无统计学意义。
在这项非随机临床试验中，HPV 疫苗接种后 RRP 的复发频率显著降低，因此 RRP 患者的疾病负担减轻。由于新发和复发性疾病患者的接种后复发病变频率无差异，因此两组患者均从 HPV 疫苗接种中获益。这些发现表明，RRP 患者越早接受 HPV 疫苗接种，疾病负担减轻的速度可能越快。
EudraCT 标识符：2011-002667-14；临床试验.gov 标识符：NCT01375868。
