# Sinonasal Inverted Papillomas: Predictors of Recurrence and Malignant Transformation

**Authors:** Ionut Tanase, Mircea-Sorin Ciolofan, Codrut-Caius Sarafoleanu, Carmen Aurelia Mogoantă, Florentina-Carmen Badea, Constantin-Ioan Busuioc, Shirley Tarabichi, Alex Milea, Ilona Mihaela Liliac, Dan Iovanescu, Gheorghe Iovanescu, Gabriela-Cornelia Musat

PMC · DOI: 10.3390/life16030442 · 2026-03-09

## TL;DR

This study identifies factors like smoking and HPV that predict recurrence and cancer transformation in a rare nasal tumor called sinonasal inverted papilloma.

## Contribution

The study identifies novel predictors of recurrence and malignant transformation in sinonasal inverted papillomas using clinical, molecular, and immunohistochemical data.

## Key findings

- Recurrence was associated with longer symptom duration, smoking, advanced stage, frontal sinus origin, HPV+, and p16 loss.
- Malignant transformation was linked to smoking but not to HPV status.
- HPV+ tumors had a higher recurrence rate compared to HPV- tumors.

## Abstract

Sinonasal inverted papillomas (IPs) are rare benign tumors with ~15% postoperative recurrence and a ~8% risk of malignant transformation, with human papillomavirus (HPV) reported as a risk factor in IP malignant transformation. To evaluate clinical, molecular and immunohistochemical factors associated with recurrence and malignant transformation in IPs. We retrospectively analyzed 73 patients with histologically confirmed IPs that were treated at three tertiary ENT centers, including radiologic data, HPV DNA detection and p16 immunohistochemistry. Univariate analysis was used to identify factors associated with recurrence and malignant transformation, and restricted exploratory multivariable logistic regression models were used to assess recurrence while minimizing overfitting. Fourteen recurrences (19%) were associated with longer symptom duration (p = 0.003), smoking (p = 0.03), advanced Krouse stage (III–IV) (p < 0.001), frontal sinus origin (p = 0.02), HPV+ DNA (50% vs. 22%, p = 0.048), and p16 loss/reduced expression (p = 0.006). Nine recurrences transformed into carcinoma (12%) and were associated with smoking (p = 0.01). HPV+ was not associated with malignancy (p = 1.00). Recurrence was associated with the advanced stage of the IP, tobacco use, longer symptom duration, frontal sinus origin, HPV+, and p16 loss/reduced expression.

## Linked entities

- **Proteins:** CDKN2A (cyclin dependent kinase inhibitor 2A)
- **Diseases:** carcinoma (MONDO:0004993)

## Full-text entities

- **Genes:** CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}
- **Diseases:** IP (MESH:D007184), IPs (MESH:D018308), benign tumors (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606], Nicotiana tabacum (American tobacco, species) [taxon 4097], Human papillomavirus (species) [taxon 10566]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13027472/full.md

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Source: https://tomesphere.com/paper/PMC13027472