Inverted papilloma: The stubbornly persistent tumor of the sinonasal cavity

The association between human papilloma virus (HPV) and diseases of the head and neck is a tremendous contemporary issue. When looking at the vast amount of data coming from numerous sources about HPV and head and neck tumors, one could be forgiven for thinking that HPV is only related to oral mucosal disease. However, the association between HPV and sinonasal papillomas has been known for many years and is nowhere more prominently seen than when discussing the pathophysiology of that most stubborn of sinonasal tumors, the inverted papilloma (IP). This tumor remains the most common benign lesion of the nasal cavity, but, despite it being an infection, it behaves like an aggressive tumor, with both local destruction and a 10–15% propensity for malignant transformation. Although the HPV origin of this disease is well understood, there remains much work to be done in understanding why this particular variant of papilloma behaves in the unique ways that it does. This issue of the American Journal of Rhinology and Allergy (AJRA), contains three important articles that directly examined this challenging surgical problem.

Brian W. Rotenberg, M.D., M.P.H., F.R.C.S.C.

First, a fascinating article by Roh et al.¹ demonstrates contrarian data that indicates that smoking, and not primary HPV infection, may be at the root cause of IP recurrence. HPV-specific data from the recurrence versus no recurrence groups is not different, whereas the smoking group had a nearly 10 times higher recurrence rate. This finding calls into question many of the commonly held beliefs about how this disease progresses. Second, Yamashita et al.² describe a new marker for IP, that being serum squamous-cell carcinoma antigen. Distinguishing IP from surrounding, more routine, sinonasal polyposis can be a pathologic challenge that often requires an invasive biopsy. This article proposes a blood test that can be used instead of biopsy, which, if upheld in further clinical work, has the potential to drastically change how IP is diagnosed. ² Third, Akkari et al³ review a series of unusual presentations of IP, which confirm what many clinicians already know in that keeping an open mind to strange findings can often let one arrive at a surprising conclusion, and nowhere is this more true than the odd manners in which IP can frequently present itself.

Quality of life (QOL) and epidemiologic analysis of outcomes are increasingly playing a role in evaluating surgical outcomes in all facets of medicine, and endoscopic sinus surgery (ESS) should be no exception. In this issue of AJRA, several articles add to the body of knowledge on this topic. Gregurić et al.⁴ review the differences of the Sino-Nasal Outcome Test 22 scores versus visual outcomes scales when comparing patients with and those without polyposis, which showed significant differences in health-related QOL between the two groups. Schlosser et al.⁵ investigated the growing recognition of the association between chronic rhinosinusitis (CRS) and other comorbidities; in this case, that of depression, which showed that depression may be more closely associated with CRS than previously realized and especially for patients with polyposis. DeConde and Soler⁶ review the epidemiologic data that evaluates the burden of illness that CRS places on society and shows that, although clinicians are focused by guidelines on sinus-specific symptoms, patients seem to be most impacted by the general-health related consequences of CRS. This novel finding has implications for health resource allocation.

Masterson et al.⁷ compare QOL outcomes for patients undergoing ESS for both fungal and nonfungal sinusitis, which shows that patients with the more severe disease phenotype associated with fungus generally experience better QOL outcomes. Nguyen et al.⁸ studies residual symptoms after ESS, an intriguing and understudied area in the surgical literature and found that, unfortunately, olfactory disturbance continues to be the least reliably improved symptom. Ahn et al.⁹ studies the role of septal deviation in asthma symptoms with a huge population base of >8000 patients and found that septal deviation is indeed associated with asthma but only in patients with nasal obstruction. Finally, Chen et al.¹⁰ compare patients undergoing conventional ESS with those undergoing extensive ESS in the setting of severe polyposis and show that the latter group has better outcomes; this article, therefore, introduces the concept that sometimes it is better to, in fact, not be conservative when operating on patients with CRS.¹⁰

Another theme of this issue of AJRA is that of new evidence in the setting of perioperative care for patients undergoing ESS. It is well known that the trauma of ESS at a microscopic level can actually damage the cilia that surgery is designed to functionally improve. Cassano et al.¹¹ demonstrate that use of hyaluronic acid, when added to nasal douches after ESS, improves both mucociliary clearance and nasal mucosa regeneration due to a faster recovery of the impaired ciliated cells. These data may add a new arm to standard postoperative care regiments. Miller et al.¹² review data that analyzes the impact of middle turbinate resection on bleeding after ESS and conclude that there is no change in major bleeding risk but that patients on anticoagulants are at an increased risk of minor bleeds after surgery. Rosen et al.¹³ conducted a systematic review of antibiotic use in endoscopic skull base surgery and show that, in general, meningitis is exceedingly rare in endoscopic relative to open procedures. The article by Zelenik et al.¹⁴ adds to the ongoing controversy regarding the association between esophageal reflux and CRS.

The molecular biology of CRS remains a mystery that proves challenging to unravel. In this issue of AJRA, several articles attempt to fill in some missing gaps in knowledge. Akkari et al.¹⁵ review the role of spleen tyrosine kinase in regard to intracellular signaling in the setting of inflammatory disease. As well, Willis et al.¹⁶ investigate the bacterial microbiome in patients with CRS and their intriguing findings indicate that swabs provided the best quality microbiome samples and that a large portion of the bacteria identified in the sinus are DNase sensitive, thus being able to differentiate between living and dead bacteria; these results have implications when assessing sinus immune functionality.

Pediatric sinonasal surgery remains a controversial topic, and this issue of AJRA adds to the discussion. Hamilos¹⁷ reviews the role of problem-based learning in teaching students about pediatric CRS, Yenigun et al.¹⁸ assess the role of the eosinophil-to-lymphocyte ratio in evaluating pediatric patients with rhinitis, and Cingi et al.¹⁹ try to assess the youngest age at which septoplasty can safely be performed. All these are interesting articles that will certainly stimulate discussion in pediatric circles.

Finally, there are three interesting articles on rhinitis in this issue of AJRA. Otsuka et al.²⁰ studies the role of bacterial colonization in Japanese cedar pollinosis and showed that neutrophilia in these patients can exacerbate symptoms. Yenigun et al.²¹ identify a possible link between dry eye and allergy. As well, Kim et al.²² found that the immunologic effects of lead exposure may be greater in people with allergic sensitization.

On behalf of the Editorial Board, I have no doubt you the reader will find this issue highly educational and relevant to your practice. May we continue to work together to better our knowledge of sinonasal disorders.