Original Study Published December 16, 2025 in the International Journal of Infectious Diseases
Study Authors:Qijian Zheng, Changchang Dun, Wenbin Lei, Guangke Wang, Weiwei Wang, Qingquan Hua, Zhen Xu, Zhe Zhang, Dapeng Lei, Dongyan Chen, Xin Wang, Yalikun Yasen, Nilipaer Alimu, Li Shi, Xiaoguang Ni, Yutong Li, Jiayu Chen, Xuelian Zhao, Shangying Hu, Hui Yang, Jun Wang, Fanghui Zhao
For adults diagnosed with recurrent respiratory papillomatosis (RRP), one of the most common questions is: What can I expect going forward?
Unfortunately, RRP does not follow the same path for every patient. Some individuals experience relatively few recurrences, while others require repeated surgeries over many years. Understanding which patients are most likely to develop aggressive disease remains one of the most important goals in RRP research.
A new nationwide multicenter study from China provides important insight into this question. Researchers analyzed adult-onset recurrent respiratory papillomatosis (AoRRP) cases from ten tertiary hospitals across seven regions of China and found a clear pattern: the younger a person was when diagnosed with adult-onset RRP, the more likely they were to have frequent, persistent recurrences.
The findings suggest that age at diagnosis may be one of the strongest predictors of long-term disease burden in adults living with RRP.
Study Abstract
To assess the demographic and clinical characteristics of Chinese adult-onset recurrent respiratory papillomatosis (AoRRP) and analyze the influence of age at diagnosis on recurrence. Histologically confirmed AoRRP cases from 10 tertiary hospitals across China's 7 regions from 2011 to 2021 were analyzed. Demographic and clinical characteristics were summarized, recurrence probabilities (1-, 3-, 5-, and 7-year) were estimated by the Turnbull method, and early-course recurrence trajectories were identified using growth-mixture modelling (GMM).
Associations between diagnostic age and recurrence were assessed using a generalized log-rank test, multivariable zero-inflated negative binomial regression, gamma regression, and multivariable logistic regression. Chinese AoRRP was diagnosed at a median age of 38 years, with peaks at 29 and 53 years; males accounted for 81.54% of cases. Hoarseness was the leading presenting symptom (85.54%). The median follow-up was 8.79 years (IQR = 5.50-11.23). Severe outcomes were observed, including aggressive AoRRP (9.85%), malignant transformation (2.46%), and mortality (0.62%). Overall, 65.85% of patients had at least one recurrence, and the recurrence density was 224.17 per 1,000 person-years.
Of the four early-course recurrence trajectories identified by GMM, the persistent (18.75%) and early-burst (12.81%) types displayed frequent recurrences shortly after diagnosis. In multivariable analysis, each additional diagnostic year reduced the total number of recurrences (IRR = 0.97, 95% CI = 0.95-0.98) and made the early-course trajectory less severe (Persistent: OR = 0.89, 95% CI = 0.85-0.93; Early-Burst: OR = 0.91, 95% CI = 0.87-0.96). Chinese AoRRP patients showed a bimodal age at diagnosis. Recurrence exhibited marked heterogeneity, with the number and pattern of relapses varying widely among patients. Overall, a younger age at diagnosis was consistently linked to a substantially heavier recurrence burden.
RRP Task Force Lay Summary
This large nationwide multicenter cohort study analyzed a decade of data from ten hospitals in China to determine how age at diagnosis influences disease patterns in adult-onset RRP. The methods involved tracking the recurrence history of over 600 patients and using advanced statistical modeling to group individuals into different "trajectories" based on the frequency of their relapses. The findings showed that a majority of patients (82%) were male, with diagnosis peaking in the late 20s and early 50s. Most importantly, the researchers discovered that the younger a patient was at diagnosis, the more frequent and persistent their recurrences were likely to be. For every additional year of age at diagnosis, the total number of required surgeries significantly decreased. The study also identified a 2.5% rate of transformation into cancer. The authors conclude that younger age at diagnosis is a key predictor of a higher disease burden, suggesting that younger adults may require more aggressive monitoring and specialized treatment strategies to manage their condition effectively.
Context Note: In juvenile-onset RRP, younger age at diagnosis (particularly younger than 5 years old) has also been associated with a more aggressive clinical course.
One of the Largest Adult-Onset RRP Studies to Date
Because RRP is rare, many studies involve relatively small patient populations. This study stands out because it evaluated patients from ten tertiary hospitals across seven regions of China over ten years.
The researchers followed patients for a median of nearly nine years, allowing them to evaluate long-term recurrence patterns rather than short-term outcomes.
This type of long-term follow-up is particularly valuable because RRP is a chronic disease. A patient may appear stable for a period of time and then experience a change in disease activity years later.
By studying recurrence over an extended period, investigators identified meaningful patterns that might not be visible in shorter studies.
What Is Adult-Onset Recurrent Respiratory Papillomatosis?
Adult-onset recurrent respiratory papillomatosis occurs when papillomas, or wart-like growths caused primarily by HPV types 6 and 11, develop in the airway after adolescence.
Symptoms commonly include:
Hoarseness
Voice changes
Chronic throat clearing
Chronic cough
Breathing difficulties in severe cases
Consistent with previous research, the most common presenting symptom in this study was hoarseness, affecting more than 85% of patients.
The Study Found Two Peaks in Age at Diagnosis
One of the most interesting findings was a bimodal age distribution.
Rather than clustering around a single age group, diagnosis occurred most commonly around:
Age 29
Age 53
This suggests that adult-onset RRP may not follow a single pattern of disease emergence.
While the reasons for this finding remain unclear, it raises important questions about the biological and environmental factors that may influence when disease becomes clinically apparent.
Future research may help explain why two distinct peaks appear among adult patients.
Most Patients Experienced Recurrence
The study reinforces a reality that many people living with RRP already know firsthand: recurrence is common.
Researchers found that:
65.85% of patients experienced at least one recurrence.
This finding highlights why RRP remains such a challenging disease despite advances in surgical techniques and emerging medical therapies.
Recurrence remains a defining feature of RRP and a primary reason patients often require ongoing medical care.
Younger Patients Had More Frequent Recurrences
The study's most important finding involved age at diagnosis.
After adjusting for other factors, researchers found that younger patients consistently experienced a greater recurrence burden.
In practical terms, this means:
More surgeries
More frequent recurrences
More persistent disease activity
Higher long-term treatment burden
The statistical analysis showed that for every additional year of age at diagnosis, the expected number of recurrences decreased.
In other words, a patient diagnosed at age 25 generally faced a higher recurrence burden than a patient diagnosed at age 45.
This relationship remained significant even after accounting for multiple clinical variables.
Researchers Identified Different Recurrence Trajectories
Not all recurrences followed the same pattern.
Using advanced statistical modeling, investigators identified four distinct recurrence trajectories.
Two of these patterns were particularly notable:
Persistent Recurrence Pattern
Approximately 18.75% of patients fell into a persistent recurrence group.
These patients experienced ongoing disease activity and repeated recurrences over time.
Early-Burst Recurrence Pattern
Approximately 12.81% of patients experienced an early-burst pattern.
These individuals experienced frequent recurrences shortly after diagnosis, creating a particularly intense early disease course.
Importantly, younger patients were more likely to belong to these higher-burden recurrence groups.
Aggressive Disease and Serious Outcomes Were Observed
Although many patients experience manageable disease, the study also documented serious outcomes.
Researchers reported:
Aggressive disease in 9.85% of patients
Malignant transformation in 2.46% of patients
Mortality in 0.62% of patients
These findings serve as an important reminder that while RRP is often described as a benign disease, it can have serious consequences in a subset of patients.
Identifying factors associated with increased disease burden remains critical to improving long-term outcomes.
What Does This Mean for Patients?
The findings do not mean that every younger adult diagnosed with RRP will develop severe disease.
Many factors influence disease progression, including:
HPV subtype
Disease extent
Treatment access
Individual immune responses
Emerging therapies
However, the study does suggest that younger adults may benefit from:
More frequent monitoring
Earlier intervention when appropriate
Care at experienced RRP centers
Discussions about adjunctive therapies
Long-term follow-up planning
Understanding risk factors can help both patients and clinicians make more informed decisions.
An Interesting Parallel With Juvenile-Onset RRP
One of the most compelling aspects of this study is how closely its findings mirror what researchers have observed in juvenile-onset RRP.
Previous studies have shown that children diagnosed at younger ages, particularly before age five, often experience:
More aggressive disease
More frequent surgeries
Higher recurrence rates
This Chinese study suggests a similar pattern may exist in adult-onset disease.
Although the biological reasons remain unclear, age at diagnosis appears to be an important predictor of disease behavior across the RRP spectrum.
Why This Study Matters
This research provides some of the strongest evidence to date that age at diagnosis plays an important role in adult-onset RRP.
By identifying younger adults as a potentially higher-risk population, clinicians may be better equipped to:
Predict disease course
Personalize follow-up schedules
Counsel patients more effectively
Identify candidates for adjunctive therapies
Allocate healthcare resources appropriately
As new treatments become available, understanding which patients are most likely to experience aggressive disease will become increasingly important.
Key Takeaways
This nationwide Chinese study analyzed adult-onset RRP cases from ten tertiary hospitals.
Most patients were male, accounting for more than 81% of cases.
Diagnosis showed two age peaks, around ages 29 and 53.
Nearly 66% of patients experienced at least one recurrence.
Younger age at diagnosis was strongly associated with more frequent recurrences.
Younger patients were more likely to experience persistent or early-burst recurrence patterns.
Researchers observed aggressive disease, malignant transformation, and mortality in a subset of patients.
The findings mirror previous observations in juvenile-onset RRP, where younger age at diagnosis is also associated with more severe disease.
Frequently Asked Questions
What is adult-onset recurrent respiratory papillomatosis?
Adult-onset RRP is a rare disease caused primarily by HPV types 6 and 11 that results in recurring papillomas within the airway after adolescence.
Does age at diagnosis affect RRP severity?
According to this study, younger adults diagnosed with RRP experienced more frequent recurrences and a greater overall disease burden than older adults.
How common is recurrence in adult-onset RRP?
This study found that approximately 66% of patients experienced at least one recurrence.
Did the study find a risk of cancer?
Yes. Researchers reported malignant transformation in approximately 2.5% of patients.
Why is this study important?
It helps identify younger age at diagnosis as a major predictor of recurrence burden, which may improve risk assessment and long-term disease management.
