Augmented reality-enhanced navigation in endoscopic sinus surgery: A prospective, randomized, controlled clinical trial.

OBJECTIVE: Endoscopic sinus surgery represents the gold standard for surgical treatment of chronic sinus diseases. Thereby, navigation systems can be of distinct use. In our study, we tested the recently developed KARL STORZ NAV1 SinusTracker navigation software that incorporates elements of augmented reality (AR) to provide a better preoperative planning and guidance during the surgical procedure. METHODS: One hundred patients with chronic sinus disease were operated on using either a conventional navigation software (n = 52, non-AR, control group) or a navigation software incorporating AR elements (n = 48, AR, intervention group). Incidence of postoperative complications, duration of surgery, surgeon-reported benefit from the navigation system and patient-reported postoperative rehabilitation were assessed. RESULTS: The surgeons reported a higher benefit during surgery, used the navigation system for more surgical steps and spent longer time with preoperative image analysis when using the AR system as compared with the non-AR system. No significant differences were seen in terms of postoperative complications, target registration error, operation time and postoperative rehabilitation. CONCLUSION: The AR enhanced navigation software shows a high acceptance by sinus surgeons in different stages of surgical training and offers potential benefits during surgery without affecting the duration of the operation or the incidence of postoperative complications. LEVEL OF EVIDENCE: 1b.

Auricular reconstruction with polyethylene implants or silicone prosthesis: A single institution experience.

Auricular reconstruction is usually necessary in patients with congenital malformations, after traumatic ear amputations or in cases of neoplastic ear disease. Thirty-nine patients who underwent an auricular reconstruction with either silicon prosthesis (21 patients) or porous polyethylene (18 patients) between 2002 and 2013 were retrospectively analyzed at a tertiary academic institution. A total of 25 male und 14 female patients were included in the study. In all, 43 implants were installed in 39 patients. An implant failure was not observed in any of the examined groups. An operative revision was necessary in 5 patients in the silicon prosthesis group (N = 21) and in 4 patients in the porous polyethylene group (N = 18). The most common side effect in the porous polyethylene group was the formation of retroauricular adhesions in 11.1 % by postoperative scaring, while in the silicone prosthesis group 71.4 % of the patients presented with skin reactions around the titanium implants. Our study shows that both techniques are valuable and should be offered to patients in cases of auricular reconstruction due to the low rate of severe complications and the good functional results of both techniques.

Reduction of post-operative pain after tonsillectomy by a local mucosal flap - a prospective, randomized, controlled clinical trial on 100 adult patients.

BACKGROUND: Tonsillectomy is one of the most frequent operations in otorhinolaryngology being associated with intense post-operative pain and an impairment of swallowing and speech. AIMS: To determine whether wound sealing with a local mucosal flap can improve patient rehabilitation. MATERIALS AND METHODS: The study was designed as a prospective, randomized, monocentric, controlled clinical trial including 100 patients. Patients were operated on using either conventional extracapsular tonsillectomy (n = 50) or a modified technique with a local mucosal flap prepared from the posterior surface of the tonsil (n = 50). Number of requested pain medications, local oedema, patient-reported pain level, post-operative haemorrhage, impairment of speech, swallowing and general condition were assessed. The study was registered at the German Clinical Trials Register. RESULTS: The mucosal flap technique significantly reduced post-operative pain [2.94 (intervention group) vs. 4.61 (control group) in an numerical analogue scale, p < .001] and the number of pain medications [6 (intervention group) vs. 1 (control group), p < .001]. CONCLUSIONS: Wound sealing with a local mucosal flap can reduce post-operative pain in tonsillectomy patients and is recommended whenever anatomically feasible. SIGNIFICANCE: This new tonsillectomy technique can help to reduce post-operative pain and thereby improve the patients' post-operative rehabilitation.

Vitamin D deficiency in head and neck cancer patients - prevalence, prognostic value and impact on immune function.

Vitamin D deficiency is frequently observed in human cancer patients and a prognostic relevance could be shown for some entities. Additionally, it is known that vitamin D can stimulate the patients' antitumor immunity. However, valid epidemiological data for head and neck squamous cell carcinoma (HNSCC) patients are sparse and functional studies on a possible connection between vitamin D and the patients' immune system are missing. 25-OH vitamin D serum levels were analyzed in 231 HNSCC patients and 232 healthy controls and correlated with clinical data and patient survival. Intra- and peritumoral infiltration with T-cell, NK-cell and macrophage populations was analyzed in 102 HNSCC patients by immunohistochemistry. In 11 HNSCC patients, NK-cells were isolated before and after vitamin D substitution and analyzed for their cytotoxic activity directed against a HNSCC cell line. Vitamin D serum levels were significantly lower in HNSCC patients compared with healthy controls. Low vitamin D levels were associated with lymphatic metastasis and a negative HPV status and were a significant predictor of poor overall survival. HNSCC patients with severe vitamin D deficiency showed significantly altered intra- and peritumoral immune cell infiltrate levels. After vitamin D substitution, the patients' NK cells showed a significant rise in cytotoxic activity. Taken together, we could show that Vitamin D deficiency is highly prevalent in HNSCC patients and is a predictor of poor survival. Vitamin D substitution used as an adjuvant in immune therapies such as cetuximab and nivolumab treatment could support antitumorigenic immune responses, thus contributing to the improvement of the patients' prognosis in the context of a multimodal therapy.

Prosthetic supply of facial defects: long-term experience and retrospective analysis on 99 patients.

INTRODUCTION: Defects in the head region may be caused by tumour treatments, injuries, as well as congenital malformations. The restoration of these defects that can be performed through reconstructive plastic surgery and/or prosthetic surgery occupies a high priority in the physical and psychological rehabilitation of the patient. The present study reports on long-term experience in supply of facial prosthesis. MATERIALS AND METHODS: The medical records of 99 patients, who had been supplied with custom-made facial prostheses between 2001 and 2011, were evaluated retrospectively. RESULTS: There were 59 male (60%) and 40 (40%) female patients. The reason for prosthetic supplement was a tumour disease in 50 patients, congenital malformation in 39 patients, and trauma in 10 patients. Fifty-three patients were treated with ear prosthesis, twenty-seven patients were treated with eye prosthesis, and nineteen patients with nasal prosthesis. 82.8% of prosthetic supplies were designed as magnetic support prostheses. The most common complication was skin redness around the implants. 10% of patients suffered the loss of the osseointegrated implants. CONCLUSION: The osseointegrated titanium implants with magnet support provide a reliable attachment for prosthesis and constitute a promising alternative to surgical reconstruction of complex facial defects.

Combined therapy for epistaxis by hereditary hemorrhagic teleangiectasia: A 3-year follow up study on 45 patients.

Hereditary hemorrhagic telangiectasia (HHT) is a mutilating disease associated with the majority of patients with recurrent epistaxis episodes. The aim of this study was to present a single institution experience with patients treated for nasal epistaxis using a combination of Nd:YAG laser and argon plasma coagulation (APC) vs Nd:YAG laser alone, with a minimum follow-up of 3 years. 45 patients (21 men, 24 women) aged from 15 to 84 years with the diagnosis of HHT were treated in the Department of Otolaryngology, Head and Neck Surgery in Homburg/Saar between 10/2002 and 10/2012 because of epistaxis, using a combination of Nd:YAG laser and APC or Nd:YAG laser alone. The observation period ranged from 36 to 120 months. 15 patients were treated with Nd:YAG laser alone and 30 patients with combined Nd:YAG laser and APC. A revision was necessary in three patients (20%) in the Nd:YAG laser group and in nine (33.3%) patients in the combined group. The difference between revision rates after the two therapy forms was not statistically significant (p = 0.492). Bipolar coagulation was additionally applied in 33 patients. There was no statistically significant difference (p = 1.00) in revision rates between patients who were additionally treated with bipolar coagulation and those who did not receive bipolar coagulation as part of their treatment. No case of postoperative septal perforation was observed. Nd:YAG laser therapy remains an established option for treating treat epistaxis in HHT patients.

Cancer of unknown primary (CUP) of the head and neck: retrospective analysis of 81 patients.

The treatment of patients with cervical lymph node metastases without detectable primary tumor remains an important challenge, until today, no standard therapy is available. The present study investigated the multimodal treatment of patients with head and neck CUP syndrome (HNCUP) and their follow-up retrospectively. 81 patients with cervical lymph node metastases without a primary tumor were treated at the Departments of Otorhinolaryngology as well as Radiotherapy and Radiation Oncology at the University of Saarland in Homburg, Germany in the period between 1991 and 2013. All patients received routine work-up consisting of CUP panendoscopy and imaging. Neck dissection was then performed in 77% of the patients. The most common histology was squamous cell carcinoma (80%). Ten percent of the patients had distant metastases. All patients underwent primary or adjuvant radiation therapy, or simultaneous radiochemotherapy. After a median follow-up of 3.5 years, the 5-year survival rate was 30%. There was a local recurrence that was known in 20/63 patients (31%) and distant metastases were documented in 19/61 M0 patients (31%). Higher grade late toxicity (grade 3-4) was observed in 12% of patients. Neck dissection and radiation therapy remains an integral part of HNCUP therapy, while the use of chemotherapy could be considered in selected cases. Prospective multicenter randomized trials would be necessary to identify the best target volume and to clarify the role of chemotherapy.

Laser CO2 tonsillotomy versus argon plasma coagulation (APC) tonsillotomy: A retrospective study with 10-year follow-up.

INTRODUCTION: Tonsillotomy is increasingly gaining acceptance as the treatment for tonsillar hyperplasia resulting in obstructive symptoms. The aim of this study was to compare the long-term results of CO2 laser tonsillotomy with those of argon plasma coagulation (APC) tonsillotomy. METHODS: The data of 64 children, aged 2-10 years (mean 4.7 years), treated in the Department of Otolaryngology, Head and Neck Surgery, in Homburg, Germany with APC (36 patients) or CO2 laser (28 patients) for tonsillar hyperplasia between June 2004 and December 2004 were available for analysis. RESULTS: Forty-five (APC: 26 patients, CO2: 19 patients) of the 64 patients (70.3%) could be contacted and were available for follow-up in a telephone survey conducted 10 years after surgery. The mean operation time was 17 min (range 10-25 min) in the APC group and 23 min (range 13-32 min) in the CO2 group (p = 0.0003). No case of intra- or postoperative bleeding was documented. One minor intraoperative complication in the form of a superficial lip burn was documented in the APC group. During the minimum 10 years of follow-up, 1 patient treated with APC underwent a surgical revision because of tonsillar regrowth, whereas in the group of patients treated with CO2, no surgical revision was needed. Regarding the parents' assessment of their children's symptoms, 89.4% of the parents of the CO2 laser group and 84.6% of the parents of the APC group reported that the overall long-term operation results of their children to be "very satisfying." Regarding complications, the need for secondary tonsillectomy, and parents' satisfaction, no statistically significant differences were found. CONCLUSIONS: Both CO2 laser tonsillotomy and APC tonsillotomy are safe procedures leading to very satisfying results with respect to intra- and postoperative complications.

Effect of 3q oncogenes SEC62 and SOX2 on lymphatic metastasis and clinical outcome of head and neck squamous cell carcinomas.

Chromosome 3q26 amplification represents a frequent alteration in head and neck squamous cell carcinomas (HNSCCs). Overexpression of 3q26 encoded genes SEC62 and SOX2 was detected in various cancers, including HNSCCs, indicating their potential function as oncogenes. In our study, we elucidated the function of SEC62 and SOX2 in HNSCC patients, with a main focus on their effect on lymphatic metastasis and patient survival. We analyzed SEC62 and SOX2 expression in tissue specimens from 65 HNSCC patients and 29 patients with cervical cancer of unknown primary (CUP); a higher SEC62 and lower SOX2 expression was observed in the lymph node metastases from HNSCC patients compared with the respective primary tumor. Lymph node metastases from CUP patients showed higher SEC62 and lower SOX2 expression compared with lymph node metastases from HNSCC patients. When proceeding from the N1 to the N3 stage, SEC62 expression in the lymph node metastases showed an increase and SOX2 expression showed a decrease. Moreover, both genes showed a highly significant relevance as prognostic biomarkers, with the worst prognosis for patients with high SEC62 and low SOX2 expression levels. In functional analyses, knockdown of SEC62 resulted in an inhibition of HNSCC cell migration while, conversely, SEC62 and SOX2 overexpression stimulated cell migration. Taken together, our study showed that the expression of the 3q oncogenes SEC62 and SOX2 affects lymphatic metastasis and cell migration in HNSCC and CUP patients and has a high prognostic relevance in these diseases.

Epithetic nasal reconstruction for nasal carcinoma: retrospective analysis on 22 patients.

Advanced nasal cancers usually demand partial or total rhinectomy followed by radiotherapy. Reconstruction of the resulting defects can be achieved by means of reconstructive plastic surgery and/or epithetic surgery. The data of 22 patients who had been treated after nasal ablation by means of custom-made silicone nasal epithesis fixed by bone-anchored magnets between 2003 and 2014 were evaluated retrospectively. There were 15 male (68.2 %) and 7 (31.8 %) female patients. The most common etiology that led to epithetic rehabilitation was a squamous cell carcinoma in 16 patients. An operative revision was necessary in two patients due to screw loss. Twenty patients were still alive with no evidence of disease after minimum follow-up of 2 years (90.9 %). Epithetic rehabilitation after nasal ablation to treat nasal malignancies is an interesting alternative to plastic and reconstructive surgery. Bone-anchored fixation using magnets can achieve a stable epithetic fixation after nasal ablation necessitating, in numerous cases, additional adjuvant therapy like radiation.

Increase of Mast Cell-Nerve Association and Neuropeptide Receptor Expression on Mast Cells in Perennial Allergic Rhinitis.

OBJECTIVES: Mast cells (MCs) and nerves play an important role in allergic rhinitis (AR), but little is known about their crosstalk in AR. The aim of this study was to investigate MC-nerve interaction in the human nasal mucosa during AR. METHODS: The association between MCs and nerves, the expression of neuropeptide receptors (neurokinin 1 receptor [NK1R], neurokinin 2 receptor [NK2R], calcitonin gene-related peptide receptor [CGRPR], and MrgX2) on MCs, and protease-activated receptor 2 (PAR2) and tyrosine receptor kinase A (TrkA) on nerve fibres in the human nasal mucosa were investigated with immunofluorescence and real-time PCR. RESULTS: The association between MCs and nerves was found to be significantly increased, although the numbers of MCs and nerve fibres were unchanged during AR. MCs expressing tryptase-chymase (MCtc) were frequently associated with nerve fibres and these contacts increased significantly in AR. Neuropeptide receptors NK1R, NK2R, and CGRPR were firstly found to be largely localised on MCs. The number of MCs expressing NK1R and NK2R, but not CGRPR, was significantly increased in AR. Interestingly, MCtc mostly expressed these neuropeptide receptors. The newly discovered tachykinin receptor MrgX2 was not expressed on nasal MCs, but was expressed on gland cells and increased in AR. Additionally, tachykinergic nerve fibres were found to express PAR2 or TrkA as receptors for MCs. CONCLUSIONS: This study revealed for the first time an increase of MC-nerve association and neuropeptide receptor expression on MCs during AR as well as nerve fibres containing receptors for MCs. These results suggest that targeting or controlling airway sensory nerve function as a modulator of MCs may prevent allergic airway inflammation such as AR.

Retrospective analysis of laser vs other therapeutic modalities for laryngeal papillomatosis: European multicenter study.

PURPOSE: Laryngeal papillomatosis can be an aggressive and potentially life-threatening disease, affecting both children and adults. Local excision is the gold standard of treatment, but recurrences are frequently inevitable. The purpose of this study was to present the experience of three institutions with different therapeutic modalities and discuss them in relation with the relevant literature. METHODS: Sixty patients underwent papilloma resection during the last decade in three institutions (Homburg/Saar and Marburg, Germany and Athens,Greece). Patient data were retrospectively analyzed for therapeutic modalities applied, rate of complications and synechia formation, necessary operations and need for tracheostomy. RESULTS: Carbon dioxide laser therapy was the most common modality applied alone or combined with other treatment modalities. No major complication was observed, while glottic synechia was the most common minor complication in 5 (8.3%) patients. Of the patient cohort 55.6% required reoperation, while no patient required tracheostomy. CONCLUSIONS: Surgical debulking with or without adjuvant treatment remains the mainstay of treatment, which mainly aims to reduce the number and frequency of recurrences since no definitive curative therapy is known so far.

Nd:YAG Laser Treatment for Extranasal Telangiectasias: A Retrospective Analysis of 38 Patients with Hereditary Hemorrhagic Telangiectasia and Review of the Literature.

BACKGROUND/AIMS: Extranasal telangiectasias are common amongst hereditary hemorrhagic telangiectasia (HHT) patients. Telangiectasias can be found at sites like the external nose, lips, oral cavity and fingers. Although not life threatening, they can be annoying for patients and lead to bleeding in some cases, necessitating treatment. METHODS: The data of 38 HHT patients treated for extranasal telangiectasias during a period of 10 years by means of Nd:YAG laser were retrospectively analyzed. RESULTS: The telangiectasias treated affected predominantly the tongue, facial skin and lips. During a minimum follow-up of 3 years, only 7 patients required a revision of surgery. CONCLUSION: This study shows that Nd:YAG laser constitutes a fast, safe and efficient therapeutic modality for the treatment of extranasal telangiectasias.

Identification of SEC62 as a potential marker for 3q amplification and cellular migration in dysplastic cervical lesions.

BACKGROUND: Chromosome 3 amplification affecting the 3q26 region is a common genomic alteration in cervical cancer, typically marking the transition of precancerous intraepithelial lesions to an invasive phenotype. Though potential 3q encoded target genes of this amplification have been identified, a functional correlation of potential oncogenic function is still missing. In this study, we investigated copy number changes and the expression level of SEC62 encoded at 3q26.2 as a new potential 3q oncogene in dysplastic cervical lesions and analyzed its role in cervical cancer cell biology. METHODS: Expression levels of Sec62 and vimentin were analyzed in liquid based cytology specimens from 107 women with varying grades of cervical dysplasia ranging from normal cases to cancer by immunofluorescence cytology. Additionally, a subset of 20 representative cases was used for FISH analyses targeting SEC62. To further explore the functional role of Sec62 in cervical cancer, HeLa cells were transfected with a SEC62 plasmid or SEC62 siRNA and analyzed for their proliferation and migration potential using real-time monitoring and trans-well systems as well as changes in the expression of EMT markers. RESULTS: FISH analyses of the swabbed cells showed a rising number of SEC62 gains and amplifications correlating to the grade of dysplasia with the highest incidence in high grade squamous intraepithelial lesions and squamous cell carcinomas. When analyzing the expression level of Sec62 and vimentin, we found a gradually increasing expression level of both proteins according to the severity of the dysplasia. In functional analyses, SEC62 silencing inhibited and SEC62 overexpression stimulated the migration of HeLa cells with only marginal effects on cell proliferation, the expression level of EMT markers and the cytoskeleton structure. CONCLUSIONS: Our study suggests SEC62 as a target gene of 3q26 amplification and a stimulator of cellular migration in dysplastic cervical lesions. Hence, SEC62 could serve as a potential marker for 3q amplification, providing useful information about the dignity and biology of dysplastic cervical lesions.

Laser surgery for Zenker's diverticulum: European combined study.

Surgical intervention is the gold standard of treatment for Zenker's diverticulum. The aim of this study was to examine the role of laser surgery in a large number of patients with this pathological entity. The data of 91 consecutive patients treated due to Zenker's diverticulum with the aid of CO2 laser in three institutions (Homburg/Saar and Marburg, Germany/Athens, Greece) during the last 10 years were retrospectively analyzed. Parameters examined were sex, age, preoperative symptoms, length of operation and complications, revision surgery necessity and degree of patient satisfaction. All patients had a minimum follow-up of one year. Dysphagia was the most common preoperative symptom (78 %). The most common minor complication was dental injury (6.6 %), but a serious complication in form of emphysema was observed in only two patients (2.2 %). A surgical revision was necessary in 8 (8.8 %) of the treated patients. The majority of treated patients was free of symptoms (86.8 %), or presented mild symptoms (9.9 %) one year after intervention, and only three patients (3.3 %) were dissatisfied. Our study shows that laser treatment of Zenker's diverticulum is an efficient operative technique associated with low complications rates and significant improvement of patients' symptoms in most of the examined cases.

Novel modification of voice prosthesis.

The undesired dilatation of the tracheooesophageal shunt after surgical implantation of voice prosthesis is a typical complication of this procedure. Temporary removal of the prosthesis and reinsertion after a short period of time is a first-line therapeutical option aiming shrinkage of the shunt. Failure of this measure generally is an indication of revision surgery. We present first experiences treating leakage problems with novel modified voice prosthesis without surgical intervention in specified cases. 11 patients (1 female, 10 male) aging between 51 and 71 years were presented with shunt leakage between 11/2008 and 11/2012 in the ENT-Department of the University Hospital of Homburg/Saar after a custom built voice prosthesis had been used initially successfully. A "Provox 2"(®) voice prosthesis was modified with two discs made of silicone each on the tracheal and oesophageal side and additionally reinforcing the diameter of the prosthesis by a silicone tube. The modified prosthesis was inserted in a retrograde way under general anesthesia, analogical to the approach used with the "Provox 1"(®)-prosthesis. The period of observation ranged between 12 and 48 months. As a measure of control swallowing of methylene blue was used. In all cases leakage suspended. Durability of the modified prosthesis ranged between 2 and 6 months. Neither the patients' complained about, nor did the physicians notice subjectively an impairment of the voice quality. Modifications of "Provox 2"(®)-prosthesis should be regarded in individual cases and constitute a reasonable alternative to revision surgery. A surgical approach is more intricate and costly, more taxing for the patient and susceptible to failure. We regard the necessity of general anesthesia for the insertion of the modified prosthesis as a disadvantage.

Modifications of transaxillary approach in endoscopic da Vinci-assisted thyroid and parathyroid gland surgery.

Endoscopic surgery for treatment of thyroid and parathyroid pathologies is increasingly gaining attention. The da Vinci system has already been widely used in different fields of medicine and quite recently in thyroid and parathyroid surgery. Herein, we report about modifications of the transaxillary approach in endoscopic surgery of thyroid and parathyroid gland pathologies using the da Vinci system. 16 patients suffering from struma nodosa in 14 cases and parathyroid adenomas in two cases were treated using the da Vinci system at the ENT Department of Homburg/Saar University and in cooperation with the Department of General Surgery in New Sant'Agostino Hospital, Modena/Italy. Two different retractors, endoscopic preparation of the access and three different incision modalities were used. The endoscopic preparation of the access allowed us to have a better view during preparation and reduced surgical time compared to the use of a headlamp. To introduce the da Vinci instruments at the end of the access preparation, the skin incisions were over the axilla with one incision in eight patients, two incisions in four patients and three incisions in a further four patients. The two and three skin incisions modality allowed introduction of the da Vinci instruments without arm conflicts. The use of a new retractor (Modena retractor) compared to a self-developed retractor made it easier during the endoscopic preparation of the access and the reposition of the retractor. The scar was hidden in the axilla and independent of the incisions selected, the cosmetic findings were judged by the patients to be excellent. The neurovascular structures such as inferior laryngeal nerve, superior laryngeal nerve and vessels, as well as the different pathologies, were clearly 3D visualized in all 16 cases. No paralysis of the vocal cord was observed. All patients had a benign pathology in their histological examination. The endoscopic surgery of the thyroid and parathyroid gland can be performed using the da Vinci system and offers an excellent, intra-operative, 3D visualization of the neurovascular structures. The new incision modalities, use of a new retractor, and endoscopic preparation of the access made the surgery easier and safer using the transaxillary access to the thyroid and parathyroid glands. The modified skin incisions allowed an improved movement of the da Vinci arms during operation.

Combination of p16(INK4a) /Ki67 immunocytology and HPV polymerase chain reaction for the noninvasive analysis of HPV involvement in head and neck cancer.

BACKGROUND: High-risk human papillomavirus (HPV) infection has been identified as a relevant risk for the development of head and neck squamous cell carcinomas (HNSCCs). As HPV status has also gained a role as a prognostic and predictive biomarker for this entity, there is a growing demand for valid HPV testing in HNSCC patients METHODS: Liquid-based cytological smears from 45 HNSCC and 20 control patients were collected and used for simultaneous immunocytochemical p16(INK4a) /Ki67 staining using a CINtec PLUS kit after the presence of tumor cells was verified in a Papanicolaou-stained slide. The same cytological suspension was used for the detection of HPV DNA by specific polymerase chain reaction (PCR). RESULTS: Tumor cells were detected in the swab material of 44 HNSCC patients corresponding to a sensitivity of 98% (44 of 45). PCR analysis revealed the presence of HPV DNA in the cytological suspension of 13 patients (13 of 65, 20%) with simultaneous p16(INK4a) /Ki67 expression by the tumor cells in 11 of these HPV DNA-positive samples (11 of 13, 85%) - a staining pattern that is strongly associated with a carcinogenic HPV infection. CONCLUSIONS: A simultaneous immunocytochemical detection of p16(INK4a) and Ki67 can reliably be performed on liquid-based cytological smears from HNSCC patients using a CINtec PLUS kit. In addition, the same cytological material can be used for the detection of HPV DNA by specific PCR. The combined results of both techniques enable better discrimination between latent and carcinogenic HPV infections as well as HPV-negative cases and thus can provide information on the prognosis of HNSCC patients and facilitate therapeutic decisions.