Recurrent Respiratory Papillomatosis : Causes and Consequences

Some manifestations of human papillomavirus (HPV) infection are indolent and self-limiting, while others cause considerable morbidity. In recurrent respiratory papillomatosis (RRP), low-risk HPV types within the respiratory tract cause wart-like lesions, typically on vocal folds. The most common symptom is hoarseness, but stridor may also occur due to airway obstruction. In a minority of patients, the disease becomes aggressive and may undergo malignant transformation. Medical records were reviewed from all patients (n=32) treated for juvenile-onset recurrent respiratory papillomatosis (JORRP) between 1975 and 1994 at Helsinki University Hospital. Eighteen patients participated in a study assessing the effect of JORRP on adult voice quality and health-related quality of life (HRQOL). Compared to age- and gender-matched controls with similar smoking habits, the quality of voice in these adult patients with a history of JORRP was significantly lower in both acoustic and perceptual analyses. Significant differences emerged neither in HRQOL, nor in subjective voice-related handicap. Despite the viral etiology, treatment of RRP is based on surgery. Patients with frequently relapsing or otherwise aggressive disease may benefit from adjuvant medical therapies, such as local injections of cidofovir. Cidofovir is an antiviral medicine officially indicated for intravenous treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). Its intravenous administration has caused nephrotoxic side-effects and neutropenia. Animal studies have raised suspicions of its carcinogenicity. According to its manufacturer, patients treated either by off-label indications, or by an unapproved route of administration (intraocular or topical) have developed severe side-effects. An international multicenter study collected data from 635 RRP patients, 275 of which were treated with cidofovir. Mean follow-up after the first cidofovir injection was 3.3 years. Differences in incidence of upper respiratory tract and tracheal malignancies were non-significant between patients treated with and without cidofovir. After local administration of cidofovir, no clinical evidence emerged for nephrotoxicity or neutropenia. Between 1975 and 2011, a total of 324 RRP patients underwent treatment at Helsinki University Hospital for laryngeal papillomas (LPs). Nine patients (2.8%) developed laryngeal squamous cell carcinoma (SCC). Expression of toll-like receptors (TLRs) 2, 4, and 9 were analyzed in laryngeal tissue specimens from these patients by immunohistochemistry (IHC). Controls were 9 RRP patients without malignant transformation, 23 patients clinically presenting with chronic laryngitis, and 19 laryngeal SCC patients without pre-existing RRP. Compared to specimens from those with chronic laryngitis and laryngeal SCC, expression of cytoplasmic TLR4 and TLR9 was significantly lower in LPs. Nuclear TLR4 staining was significantly lower in LPs undergoing transformation into laryngeal SCC, than in LPs without malignant conversion. In laryngeal SCCs, high cytoplasmic staining for TLR4 was associated with higher grade and advanced T stage. HPV infections are spread through direct contact from skin or mucosa during sexual contact, and from mother to child during labor. Five RRP patients and five patients with genital warts participated with six physicians and twelve nurses in a study investigating transmission of HPV from patients to the oral mucosa and surgical gloves and masks of health care personnel during carbon dioxide (CO2) laser treatment. HPV deoxyribonucleic acid (DNA) was detected by polymerase chain reaction (PCR) on the surgical gloves, but not on the surgical masks or oral mucosa of health care personnel. Provided that protection is sufficient during CO2 laser treatment, the risk for HPV transmission to health care personnel seems low.Osa ihmisen papilloomaviruksen (engl. human papillomavirus, HPV) aiheuttamista infektioista on luonteeltaan hyvänlaatuisia ja itsestään rajoittuvia, kun taas osa tuottaa potilaille merkittävää haittaa. Hengitysteissä ns. matalan syöpäriskin HPV-tyypit aiheuttavat taudin, jossa tyypillisesti äänihuulissa esiintyy toistuvasti hyvänlaatuisia papilloomia (engl. recurrent respiratory papillomatosis, RRP). Äänenkäheys on tavallisin oire, mutta myös myös hengenahdistusta voi esiintyä, jos papilloomat ahtauttavat ilmatien. Pienellä osalla potilaista tauti on aggressiivinen ja voi muuttua pahanlaatuiseksi. Tässä väitöskirjatyössä käytiin läpi kaikkien niiden potilaiden (n=32) sairauskertomukset, joita oli hoidettu lapsuusiällä alkaneen kurkunpään papillomatoosin takia HYKS korvaklinikalla vuosina 1975-1994. Kahdeksantoista potilasta osallistui tutkimukseen, jossa selvitettiin taudin vaikutuksia aikuisiän äänen- ja elämänlaatuun. Potilaiden akustisesti - ja aistinvaraisesti arvioitu äänen laatu oli merkittävästi heikompi kuin ikä-, tupakointi- ja sukupuolivakioitujen verrokkien. Subjektiivisesti arvioitu terveyteen liittyvä elämänlaatu ja äänihäiriön aiheuttama haitta ei poikennut merkittävästi potilaiden ja verrokkien välillä. Hengitysteiden papilloomia hoidetaan kirurgisesti vaikka tauti on viruksen aiheuttama. Usein toistuvassa tai muuten aggressiivisessa taudissa joudutaan turvautumaan ns. liitännäishoitoihin, kuten paikallisiin sidofoviiri-injektioihin. Sidofoviiri on antiviraalinen lääkeaine, jota annetaan virallisen käyttöaiheen mukaan suonensisäisenä infuusiona sytomegaloviruksen aiheuttamaan verkkokalvontulehdukseen AIDS-potilailla. Suonensisäisessä käytössä sidofoviirin on todettu aiheuttavan munuaishaittoja ja neutropeniaa. Epäilyt sidofoviirin karsinogeenisuudesta perustuvat lähinnä eläinkokeisiin. Lääkkeen valmistaja on raportoinut hankalia sivuvaikutuksia potilailla, joilla sidofoviiria on annosteltu vastoin alkuperäistä indikaatiota, kuten silmään tai iholle. Kansainväliseen monikeskustutkimukseen kerättiin retrospektiivisesti tiedot 635:stä hengitysteiden papillomatoosia sairastavasta potilaasta. Näistä 275 oli saanut sidofoviiria. Sidofoviiripotilaiden seuranta-ajan keskiarvo oli 3.3 vuotta ensimmäisen injektion jälkeen. Sidofoviiria saaneilla papilloomapotilailla ei todettu enempää ylähengitysteiden - tai henkitorven pahanlaatuisia kasvaimia kuin niillä potilailla, joiden papilloomia hoidettiin ilman sidofoviiria. Tutkimuksessa ei saatu lisänäyttöä siitä, että sidofoviiri aiheuttaisi munuaisvaurioita tai neutropeniaa ylähengitysteiden papilloomien paikallisissa injektioissa. HYKS korvaklinikalla hoidettiin vuosina 1975-2011 yhteensä 324 kurkunpään papillomatoosia sairastavaa potilasta, joista yhdeksälle (2.8%) kehittyi kurkunpään levyepiteelisyöpä. Tutkimuksessa analysoitiin tollin kaltaisten reseptorien (engl. toll-like receptors, TLR) 2, -4 ja -9 immunoekspressiota näiden potilaiden papillooma- ja syöpäkudoksessa. Verrokkeina oli yhdeksän kurkunpään papilloomaa jotka eivät pahanlaatuistuneet, 23 näytettä kroonista laryngiittia sairastavilta potilailta, sekä 19 näytettä kurkunpään levyepiteelisyövistä joita ei edeltänyt papillomatoosi. Sytoplasminen TLR4- ja TLR9-ekspressio oli merkittävästi matalampi kurkunpään papilloomissa kuin kroonisissa laryngiiteissa tai kurkunpääsyövissä. Tuman TLR4-ekspressio oli merkittävästi matalampi niissä papilloomissa jotka muuttuivat pahanlaatuisiksi verrattuna ei-malignisoituneisiin papilloomiin. Kurkunpään levyepiteelisyövissä korkea sytoplasman TLR4-ekspressio oli yhteydessä kohtalaiseen - tai huonoon erilaistumisasteeseen, sekä pidemmälle edenneeseen tautiin. HPV:n tiedetään tarttuvan iholta tai limakalvolta seksikontakteissa ja mm. synnytyksen yhteydessä äidiltä lapselle. Tässä tutkimuksessa analysoitiin PCR-menetelmällä HPV DNA:n leviämistä hoitohenkilökunnan suun limakalvoille, sekä leikkauskäsineisiin ja maskeihin, kun he hoitivat hiilidioksidilaserilla potilaiden kurkunpään papilloomia ja genitaalialueen kondyloomia. Tutkimukseen osallistui viisi kurkunpään papilloomien - ja viisi genitaalialueen kondyloomien takia hoidettavaa potilasta, sekä kuusi lääkäriä ja 12 hoitajaa. HPV DNA:ta löytyi hoitohenkilökunnan hanskoista, mutta ei maskeista eikä suun limakalvoilta. Löydökset viittaavat siihen, että hoitohenkilökunnan riski saada HPV-tartunta potilaalta hiilidioksidilaserhoidon yhteydessä on vähäinen, kun asianmukaisia suojavarusteita käytetään

Humant papillomvirus vid cancer i huvud-halsregionen

English summar

Enteral tube feeding of head and neck cancer patients undergoing definitive chemoradiotherapy in the Nordic Countries : Survey of the Scandinavian Society for Head and Neck Oncology

Purpose We assessed current policies and perceptions of enteral tube feeding in head and neck cancer (HNC) patients undergoing chemoradiotherapy (CRT). A web-based survey was used to compare the timing and method of tube feeding within and between the five Nordic countries, covering a population of 27 million. Methods From each of the 21 Nordic university hospitals, one oncologist and one otorhinolaryngology-head and neck (ORL-HN) surgeon responded to a survey. The respondents were asked whether tube insertion before the onset of CRT, or during CRT as required (prophylactic vs. reactive) was preferred. The use of a pretreatment nutritional screening tool and the choice of feeding route (nasogastric vs. gastrostomy tube) were assessed. In total, we analyzed responses from 21 oncologists and 21 ORL-HN surgeons. Results A tendency was observed towards decreasing the use of a PEG tube. Of the 21 university hospitals, only 2 (10%) reported using a prophylactic PEG tube in over half of HNC patients undergoing definitive CRT. The preferred method for reactive tube feeding was by a NG tube in 14 of 21 (67%), and by a PEG in 7 of 21 (33%). In general, both oncologists and ORL-HN surgeons were content with their current policy. Conclusions The practices for enteral tube feeding in HNC management vary within and between the Nordic countries. We suggest that unified protocols for tube feeding should be developed for this patient population.Peer reviewe

Acute epiglottitis after COVID-19 infection

In patients with acute epiglottitis, the possibility of COVID-19 should be ruled out. Repeated nasofiberoscopy examinations or a tracheostomy, which may produce infectious aerosols, may be required.Peer reviewe

Pretreatment tumor sampling and prognostic factors in patients with soft-tissue sarcoma of the head and neck

Correction: DOI10.1007/s00405-021-07205-6 Early AccessDEC 2021Background Insufficient preoperative work-up and consequent intralesional or marginal resection of soft-tissue sarcomas of the head and neck (STSHNs) is common. Methods This retrospective cohort study comprised 63 patients with STSHN treated at the Helsinki University Hospital between 2005 and 2017. We assessed the effect of pretreatment tumor sampling on surgical margin status and need for supplemental surgery, as well as prognostic factors and survival. Results The lack of representative pretreatment biopsy specimen was associated with unfavorable margin status. Primary surgery at a non-academic center was associated with need for supplemental surgery. The 3-year overall survival (OS) was 68%, disease-specific survival (DSS) 71%, and recurrence-free survival (RFS) 61%. Higher tumor grade and primary tumor size over 5 cm were associated with reduced DSS. Conclusions Diagnosis and management of STSHNs should be centralized to experienced academic centers. Decision-making between needle biopsy, open biopsy, or upfront radical surgery depends on tumor location and size.Peer reviewe

ALS patients in otorhinolaryngology : A retrospective study

Objectives Given its rarity and the lack of clear clinical markers, amyotrophic lateral sclerosis (ALS) remains a diagnostic challenge. Because bulbar-onset ALS (buALS) presents with impaired speech or swallowing, patients are often primarily referred to an otolaryngologist (ORL) or phoniatrician. The objectives of this retrospective cohort study were to analyze the role of ORLs and phoniatricians in ALS diagnostics and treatment and the potential diagnostic delay related to initial visit to aforementioned specialists. Methods We reviewed data for all 327 patients treated for ALS through the Hospital District of Helsinki and Uusimaa (HUS) between 2010 and 2014, focusing specifically on 110 (34%) patients presenting with bulbar nerve onset (buALS). Their presenting symptoms, referral to specialized care, and delay in referral to a neurology clinic were assessed. Indications and findings from swallowing studies were reviewed as well as the incidence of percutaneous endoscopic gastrostomy (PEG) and tracheostomy. Results Among the 110 patients with buALS, 64 (58%) were primarily referred to a neurologist, 28 (25%) to an ORL, and five (5%) to a phoniatrician. The most common presenting symptom was dysarthria in 89 patients, (81%), followed by dysphagia in 26 (24%). In most cases, an ORL or phoniatrician suspected a neuromuscular disease; however, in eight (24%) cases, the neurological etiology of symptoms was missed. Overall, 49 (45%) patients underwent a swallowing study and 86 (78%) patients underwent PEG placement. Conclusions Among buALS patients, 30% initially consulted an ORL or phoniatrician and 45% underwent a swallowing study. Based on our results, swallowing studies rarely lead to immediate PEG placement. An initial visit to other specialists had no impact on diagnostic delays or survival.Peer reviewe

The presence of minor salivary glands in the peritonsillar space

Peritonsillar abscess (PTA) is traditionally considered only a purulent complication of acute tonsillitis (AT), but may be related to infection of minor salivary glands. We analysed the presence of peritonsillar minor salivary glands and inflammation patterns in 114 adult tonsils representing three patient groups: recurrent AT, chronic tonsillitis (CT), and PTA. Samples acquired from elective tonsillectomies were stored in formalin, and after preparation were microscopically examined for inflammation and fibrotic changes. Clinical features and histological characteristics were compared between the groups. Of all tonsils, the minor salivary glands were present in 77 (67.5%). Glands located near the tonsillar tissue showed signs of infection in 73 (94.8%), while only 3 (15.0%) of 20 glands located deeper in the peritonsillar space were infected. Compared to patients with recurrent AT and CT, those with PTA more often presented with periductal inflammation, p <0.011 (PTA 82.1%, AT 42.9%, and CT 63.6%). The majority of our 114 tonsillectomy specimens, collected from patients with AT, CT, or PTA, presented with infected minor salivary glands, and inflammation of the peritonsillar space glands was evident. To further elucidate the association between these glands and PTA, tonsillar samples should be collected and analysed from patients during the acute phase of infection.Peer reviewe

Peritonsillar abscess may not always be a complication of acute tonsillitis: A prospective cohort study

The present study aimed to specify diagnostics for peritonsillar abscesses (PTAs) and to clarify the role of minor salivary glands. This prospective cohort study included 112 patients with acute tonsillitis (AT) and PTA recruited at a tertiary hospital emergency department between February and October 2017. All patients completed a questionnaire concerning their current disease. Serum amylase (S-Amyl) and C-reactive protein (S-CRP) levels, tonsillar findings, and pus aspirate samples and throat cultures were analyzed. Eight of 58 PTA patients (13.8%) had no signs of tonsillar infection. The absence of tonsillar erythema and exudate was associated with low S-CRP (pPeer reviewe

Survival and Larynx Preservation in Early Glottic Cancer : A Randomized Trial Comparing Laser Surgery and Radiation Therapy

Purpose: The prognosis of glottic T1a laryngeal squamous cell carcinoma (LSCC) is excellent with both transoral laser surgery (TLS) and radiation therapy (RT). Our aim was to compare TLS and RT treatment results in a randomized study. Methods and Materials: Of 56 male patients with glottic T1a LSCC, 31 were randomized for TLS and 25 for RT. Survival and larynx preservation data were collected from medical records. Results: Five-year overall survival (OS) was 87%, disease-specific survival (DSS) was 97%, and recurrence-free survival (RFS) was 81% in patients treated with TLS. Five-year OS was 92%, DSS was 100%, and RFS was 88% in patients treated with RT. The primary treatment method was not associated with OS, RFS, or DSS in a log-rank test. The larynx preservation rate was similar in both groups (TLS, 97%; RT, 92%; P = .575). Conclusions: In a prospective randomized setting oncological outcomes of both treatment modalities (TLS or RT) for T1a LSCC were similar. (C) 2022 Elsevier Inc. All rights reserved.Peer reviewe

Serum matrix metalloproteinase 8 and tissue inhibitor of metalloproteinase 1 : Potential markers for malignant transformation of recurrent respiratory papillomatosis and for prognosis of laryngeal cancer

Background Biomarkers that could predict malignant transformation of recurrent respiratory papillomatosis (RRP) would be useful in patient follow-up. We investigated whether serum matrix metalloproteinase 8 (MMP-8) and tissue inhibitor of metalloproteinase 1 (TIMP-1) could predict malignant transformation of RRP and whether they associate with survival in laryngeal squamous cell carcinoma (LSCC) without preexisting RRP. Methods We analyzed serum MMP-8 (S-MMP-8) and serum TIMP-1 (s-TIMP-1) in 114 patients: 55 were treated for RRP and 59 for LSCC without preexisting RRP. Five patients with RRP developed LSCC during follow-up. Results Elevated S-MMP-8 level in RRP was associated with malignant transformation (P = .01). Compared to patients with RRP, S-MMP-8 in patients with LSCC was significantly higher (P <.001). Increased S-TIMP-1 level in LSCC was associated with poor overall survival (P = .02) and recurrence-free survival (P = .05). Conclusion In RRP, high S-MMP-8 may predict malignant transformation. In LSCC, elevated S-TIMP-1 is connected to poor survival.Peer reviewe