Joanna Jackowska

Safety of intralesional cidofovir in patients with recurrent respiratory papillomatosis: an international retrospective study on 635 RRP patients

Intralesional use of cidofovir (Vistide®) has been one of the mainstays of adjuvant therapy in patients with recurrent respiratory papillomatosis (RRP) since 1998. In 2011, a communication provided by the producer of cidofovir addressed very serious side effects concerning its off-label use. As this was a general warning, it was inconclusive whether this would account for its use in RRP. The aim of this study is to determine whether nephrotoxic, neutropenic, or oncogenic side effects have occurred after intralesional use of cidofovir in patients with RRP. Update of recent developments in RRP, a multicentre questionnaire and a multicentre retrospective chart review. Sixteen hospitals from eleven countries worldwide submitted records of 635 RRP patients, of whom 275 were treated with cidofovir. RRP patients received a median of three intralesional injections (interquartile range 2–6). There were no statistical differences in occurrence of neutropenia or renal dysfunction before and after cidofovir. There was no statistical difference in occurrence of upper airway and tracheal malignancies between the cidofovir and the non-cidofovir group. In this retrospective patient chart review, no clinical evidence was found for more long-term nephrotoxicity, neutropenia or laryngeal malignancies after the administration of intralesional cidofovir in RRP patients.

HPV vaccination in head and neck HPV-related pathologies.

Recent data demonstrate that human papilloma virus (HPV) plays a role in pathologies other than ano-genital cancers, specifically head and neck malignancies, and non-cancerous conditions such as recurrent respiratory papillomatosis (RRP). High-risk HPV16 and 18, and low risk HPV6 and 11 play the main role in HPV-related pathologies. As more and more information about the role of HPV infection in non-cervical diseases is amassed, additional questions about whether prophylactic HPV vaccines will effectively prevent these conditions are raised. HPV vaccination programs for the cervical pathology are being implemented worldwide. In the United States, the US Food and Drug Administration (FDA) approved the quadrivalent HPV vaccine for girls in 2006 and for boys in 2011. These vaccination programs were aimed at the genital, HPV-related lesions, and there was not much recognition at that time of how HPV vaccination programs might affect oral HPV infection, which is a risk factor for the development of HPV-related head and neck cancers. Vaccination has proved to be a successful policy, and an extant recommendation is aimed at preventing HPV and associated cervical and other anogenital cancers with the routine use of HPV vaccines for males and females. However, HPV vaccines are presently not recommended for preventing oropharyngeal cancer (OPC), although they have been shown to be highly effective against the HPV strains that are most commonly found in the oropharynx. This review is aimed at presenting the evidence-based knowledge concerning HPV vaccination and highlighting the trials and strategies for vaccine administration in HPV-dependent head and neck pathologies.

HPV vaccination to prevent oropharyngeal carcinoma: What can be learned from anogenital vaccination programs?

Human papillomavirus (HPV) infections are well known causes of anogenital cancers. Recent studies show that HPV also plays a role in oropharyngeal cancer (OPC). A review on the role of HPV vaccination in the prevention of head and neck squamous cell carcinoma (HNSCC) with special emphasis on OPC was conducted and available vaccines and vaccination strategies in HNSCC and OPC are discussed. Prophylactic vaccination is known to be effective for prevention of anogenital HPV infection and precursor lesions in the cervix and anus. While the value of vaccination for prevention of OPC and possibly as an adjuvant treatment is still an open question, evidence to date supports the possibility that HPV vaccination may prove to be effective in reducing the incidence of this malignancy.

Age of onset of recurrent respiratory papillomatosis: a distribution analysis

Distribution of age of onset of recurrent respiratory papillomatosis (RRP) is generally described to be bimodal, with peaks at approximately 5 years and 30 years. This assumption has never been scientifically confirmed, and authors tend to refer to an article that does not describe distribution. Knowledge of the distribution of age of onset is important for virological and epidemiological comprehension. The objective of this study was to determine the distribution of age of onset of RRP in a large international sample.

Global miRNA Expression Profiling Identifies miR-1290 as Novel Potential oncomiR in Laryngeal Carcinoma

Background Laryngeal squamous cell carcinoma (LSCC) is the most common group among head and neck cancers. LSCC is characterized by a high incidence in Europe. With the aim of better understanding its genetic background we performed global miRNA expression profiling of LSCC cell lines and primary specimens. By this approach we identified a cohort of 33 upregulated and 9 downregulated miRNA genes in LSCC as compared to epithelial no tumor controls. Results Within this group we identified overexpression of the novel miR-1290 gene not reported in the context of LSCC before. Using a combined bioinformatical approach in connection with functional analysis we delineated two putative target genes of miR-1290 namely ITPR2 and MAF which are significantly downregulated in LSCC. They are interesting candidates for tumor suppressor genes as they are implicated in apoptosis and other processes deregulated in cancer. Conclusion Taken together, we propose miR-1290 as the new oncomiR involved in LSCC pathogenesis. Additionally, we suggest that the oncogenic potential of miR-1290 might be expressed by the involvement in downregulation of its target genes MAF and ITPR2.

Narrow-band imaging (NBI) for improving the assessment of vocal fold leukoplakia and overcoming the umbrella effect

Background It is crucial to find a balance between functional and oncological outcome when choosing an adequate method for the management of vocal fold leukoplakia. Therefore, a detailed examination is a milestone in the decision-making process. Aim To examine whether narrow-band imaging (NBI) can be helpful in vocal fold assessment in the case of leukoplakia and how to overcome the “umbrella effect”- understood as the submucosal vascular pattern hidden under the plaque. Material and methods Prospective cohort of 41 consecutive patients. Inclusion criteria: vocal fold leukoplakia, no previous procedures (surgery, radiotherapy), and preoperative endoscopy with an optical filter for NBI. Two groups: “suspicious” and “normal”, according to the submucosal microvascular pattern of peripheral regions of the mucosa surrounding the plaque, were distinguished. Patients were qualified for a full-thickness or partial-thickness biopsy, respectively. Criteria defining suspected characters were well-demarcated brownish areas with scattered brown spots corresponding to type IV, Va, Vb, and Vc NI classifications. Results In 22/41 (53.7%) patients with “suspected” microvascular pattern, full-thickness biopsy was performed. Moderate and severe dysplasia was revealed in 15 type IV and 7 type Va NI patients. In 19/41 (46.3%) patients with proper NBI vessel pattern treated by partial-thickness biopsy, hyperkeratosis was diagnosed. There was a strong correlation between the NBI pattern and final histology: Chi2 (2) = 41.0 (p = 0.0000). Conclusion The results demonstrate that NBI endoscopic assessment of the submucosal microvascular pattern of mucosa surrounding the plaque can be an effective method to categorise the risk in vocal fold leukoplakia prior to treatment.

Voice estimation in patients after reconstructive subtotal laryngectomy

BackgroundTreatment of laryngeal cancers, may include surgery, radiotherapy, chemotherapy, or a combination. Total laryngectomy (TL) has been the standard surgical treatment. Partial laryngectomy procedures were performed, their advantage over TL is preservation of laryngeal functions.MethodsThe investigation was carried out on a group of 20 patients (3 female and 17 male), who underwent surgery according the techniques mentioned above. The methods of investigation were based on perceptual voice estimation (GRBAS), videolaryngostroboscopy, acoustic voice analysis, aerodynamic measure maximum phonation time, voice self-assessment (VHI).Results and ConclusionsThe perceptual voice estimation revealed a good phonation result in only 3 cases after using surgery with the Calearo method as well as the best results of MPT. The VHI reflected severe voice handicap in 2 patients (26 to 40 points). No statistically significant differences were observed between the values of the acoustic parameters in MDVP analysis after following operation -CHEP, Calearo, Sedlacek.

Zabiegi rekonstrukcyjne w wielkich guzach gruczołów ślinowych

OBJECTIVE Evaluation the outcome after extensive surgery of salivary glands tumors with simultaneous reconstruction of soft tissue and skin defect. MATERIAL In the period 2007-2011, surgery treatments performed in 295 of major salivary glands. 31 patients underwent surgery due to malignant parotid gland tumors: 19 women (61%) and 12 men (39%). In 8 (26%) presented skin infiltration. 10 (32%) patients had facial palsy between II-IV degree (House Brackmann scale). The radiographic findings in some patients showed infiltration of the deep lobe of parotid gland, external auditory canal, infiltration of mastoid process, skull base and the subtemporal fossa. METHODS Of the 31 patients in 13 (42%) reconstruction techniques with muscle cutaneous trapezius flap were applied in 4 (31%) patients. In group of 7 (54%) patients using a muscle flap based on the sterno-cleido-gland, in 2 (15%) patients defects were covered using the free anterior lateral thigh flap. RESULTS In all patients, healing proceeded normally. In the operated patients, one patient did not receive radical surgery due to the infiltration of the skull base. Length of hospitalization ranged between 7-21 days. In no case was lost flap, also there was no local complications at the donor. CONCLUSIONS The choice of treatment for malignant parotid gland tumors which are usually radioresistant is surgical resection. In patients with extensive tumors with infiltration of neighbouring organs reconstruction with use of distant flaps are recommended. It provides a good oncological and aesthetic result.

Schemat postępowania i wstępne wyniki leczenia brodawczaków krtani dotkankowym preparatem cidofovir

Summary Introduction Recurrent respiratory papillomatosis (RRP) is a rare disease in children and adults. It is characterized by proliferation of benign squamous cell papillomas within the respiratory-digestive tract, predominantly the larynx. Standard treatment consists of surgical excision of papillomata to maintain airway patency and voice quality. For last several years cidofovir is the most contemporary adjuvant anti-viral treatment for recurrent respiratory papillomatosis and its topical use is widely described. Material and methods Intralesional cidofovir therapy was given to 20 patients treated for laryngeal papillomas in the Department of Otolaryngology in Poznan between I-XII.2009. The character of the lesion differed: from one anatomical site and moderate growth to four or five localizations with heavy extension. The number of cidofovir injections per patient varied from one to six times and the volume of solution ranges from 1–12 ml. The cidofovir injections were combined with laser or mechanical excision of the lesions. In disperse papillomata the injections administered in particular anatomical sites in 4–6 weeks period. In massive lesions injections were repeated in the same anatomical site. Results Complete remission was observed in 3 out of 20 patients. 12 patients show remission in a place of cidofovir injection. In 4 patients during the 4 week observation new foci of papillomatosis occurred. In two patients hepatic toxic side effect were observed. Conclusions Intralesional cidofovir injection has been shown to be an effective an safe therapy for laryngeal papilloma and should be considered in those patients who experienced disease relapse.

The Knowledge of the Role of Papillomavirus—Related Head and Neck Pathologies among General Practitioners, Otolaryngologists and Trainees. A Survey-Based Study

Objectives The aim of the survey was to introduce knowledge of HPVs role in head and neck pathologies to general physicians (GPs), otorhinolaryngologists (ENTs) and newly graduated doctors, as well as to promote HPV-related diseases prevention. Study Design Cross-sectional study. Methods Self-designed questionnaire was sent to 2100 doctors. A total of 404 doctors, including 144 ENTs, 192 GPs and 68 trainees, responded. Results The majority of ENTs (86.8%) had contact with recurrent respiratory papillomatosis (RRP) and oropharyngeal cancers (OPCs) patients; in contrast, the majority of GPs (55.7%) did not (p = 0.00). The knowledge of HPV aetiology of cervical cancer versus OPCs and RRP was statistically higher. 7% of ENTs, 20% of GPs and 10% of trainees had not heard about HPV in oropharyngeal diseases. Women had greater knowledge than men. Both in the group of GPs and ENTs, 100% of respondents had heard about the impact of vaccination on the reduction of cervical cancer incidence. Only 39.11% of respondents had heard about the possibility of using vaccination against HPV in RRP—ENT doctors significantly more often than GPs and trainees (p = 0.00). Only 28.96% of physicians had heard about the potential value of HPV vaccination in preventing OPCs, including 44.44% of ENT doctors, 23.44% of GPs and 11.76% of trainees (p = 0.00). The doctors from district hospitals showed lower level of knowledge compared with clinicians (p = 0.04). Conclusions The different levels of knowledge and awareness of HPV issues highlight the need for targeted awareness strategies in Poland with implementation of HPV testing and vaccination. The information should be accessible especially to those with lower education levels: ENTs from small, provincial wards, GPs from cities of < 200 000 inhabitants and older physicians. The incorporation of HPV issues into the studies curriculum would be fruitful in terms of improving the knowledge of trainees.