Impact of HPV infection on oral squamous cell carcinoma

Non-steroidal anti-inflammatory drugs (NSAIDs) have long been suspected of negatively affecting fracture healing, although numerous disputes still exist and little data are available regarding diclofenac. Glucocorticoids interfere in this process over a similar and even broader mechanism of action. As many previously conducted studies evaluated either morphological changes or biomechanical properties of treated bones, the conjunction of both structural measures is completely missing. Therefore, it was our aim to evaluate the effects of diclofenac and prednisolone on the fracture callus biomechanically, morphologically and by 3-dimensional (3D) microstructural analysis. Femura of diclofenac-, prednisolone- or placebo-treated rats were pinned and a closed transverse fracture was generated. After 21 days, biomechanics, micro-CT (μCT) and histology were examined. The diclofenac group showed significantly impaired fracture healing compared with the control group by biomechanics and μCT (e.g. stiffness: 57.31 ± 31.11 N/mm vs. 122.44 ± 81.16 N/mm, p = 0.030; callus volume: 47.05 ± 15.67 mm3 vs. 67.19 ± 14.90 mm3, p = 0.037, trabecular thickness: 0.0937 mm ± 0.003 vs. 0.0983 mm ± 0.003, p = 0.023), as confirmed by histology. Biomechanics of the prednisolone group showed obviously lower absolute values than the control group. These alterations were confirmed in conjunction with μCT and histology. The inhibiting effects of both substances were not only mediated by absolute parameters (e.g. breaking load, BV), but we have shown, for the first time, that additional changes occurred in the microstructural bony network. Especially in patients at risk for delayed bone healing (arteriosclerosis, diabetes mellitus, smoking), the administration of these drugs should be weighed carefully.

The current controversial discussion on the disease-specific survival of patients with human papillomavirus (HPV)-positive (+) and -negative (-) squamous cell carcinoma (SCC) of the head neck region was the motivation for the present meta-analysis. Different detection methods for HPV are available, though these often lack sensitivity. As a consequence, there may be false interpretation of HPV positivity. A bias concerning HPV status and therefore also survival rates is serving a non-durable relevance in the discussion of tailored therapies. A literature search was performed via the online database PubMed/NCBI, and data extraction and statistical analysis were conducted. A total of 139 studies published between 2004 and 2014 were evaluated in the present meta-analysis. The HPV detection methods, patient characteristics, tumor localizations and stages, as well as (neo-) adjuvant therapies and survival times were analyzed. The average incidence rates of HPV+ patients with oropharyngeal tumors were higher than those of patients with cancers of other regions of the head and neck. Upon evaluating the results of different detection methods no significant differences were identified. We have compared the HPV incidence rates of each detection method, when studies have used more than one. Regarding overall survival, the pooled adjusted hazard ratio (HR) for oropharyngeal SCC was 0.31 [95% confidence interval (CI)=0.27-0.36]. Unfortunately, only 3 equivalent studies were available on nonoropharyngeal tumors, for which the pooled adjusted HR was 1 (95% CI=0.73-1.36). Overall, the evaluation demonstrated that the survival rates reported in numerous studies were not evaluated multifactorially and important confounders were excluded from the statistics. The HPV detection methods used were often not sufficient in representing HPV positivity. In addition, oropharyngeal and oral SCCs were assessed together in the localization. The widely differing number of HPV+ patients in each of the various studies may be explained by insufficient detection methods and by a lack of localization distinction. The considerations of a tailored therapy according to HPV status should be rejected based on the present information. The previously published studies should be read critically and do not represent a basis for therapeutic decisions.

The diagnosis of cancer and its treatment have an incomparable impact on a patient’s life. In the early postoperative stages after the surgical treatment of oral squamous cell carcinoma (OSCC), functions and well-being are limited, which leads to a fundamental decline of the quality of life (QoL). To date, no studies have been performed that focus on the development of special aspects during the time of the in-patient stay of OSCC patients. With the results of this cross-sectional study, we are able to identify those patients who tend to require special support. This cross-sectional study determined the postoperative QoL with a questionnaire (QU) that was handed out twice to OSCC patients after surgery during their inpatient stay. The questions were based on the European Organisation for Research and Treatment of Cancer (EORTC)’s Quality of Life Questionnaire (QLQ)-C30 and QLQ-H&N35. In our study, we found that for postoperative OSCC patients, eating, swallowing and speech were influenced the most. After decannulation, tracheotomy showed no impact on functions. Social contact was impaired at both timepoints. Especially female patients consider themselves to be more impaired on the scale of social contact. QoL should be checked with a standardized QU as an established tool during hospitalization in every oncology department. Only this procedure can pinpoint those patients who have struggles with their surgical outcome and need more assistance.

Long‑term survival in cases of head and neck squamous cell carcinoma, particularly oral squamous cell carcinoma (OSCC), remains a rare achievement in the field of clinical oncology. In recent years, the theory of cancer stem cells (CSCs) has emerged and been used to offer explanations for tumour recurrence and metastasis. The present aim was to investigate the role of aldehyde dehydrogenase 1 (ALDH1) as a CSC‑marker for OSCC and to determine the role of p16ink4a, which is also a surrogate marker of human papilloma virus (HPV), in the expression of ALDH1. The study cohort comprised of 186 surgically‑treated cases of OSCC. The primaries were located in the oral cavity. The expression of the CSC marker (CSCM) ALDH1 was evaluated via immunohistochemistry (IHC) of a tissue microarray. HPV detection was performed by polymerase chain reaction and an HPV Array kit. Furthermore, the IHC expression of p16ink4a was also analysed. Risk regression models as the Kruskal Wallis test was used to assess the association of CSCM and p16ink4a expression with tumour size and lymph node metastasis, and cox proportional hazards were analysed. Additionally, coexpression of the markers ALDH1 and p16ink4a was analysed with regard to associations with tumour classification. Overall, high expression of ALDH1 in lymph nodes was significantly associated with Union for International Cancer Control (UICC) stage IV (P=0.044) and T4 stage cancer (P=0.03). p16ink4a positivity, in cases of HPV negativity, was associated with worse survival rate compared with that of the total cohort (P=0.048). Collectively the data indicate that ALDH1 expression may be suitable for detection of unfavourable prognosis in OSCC patients, based in part on its apparent role as a marker of metastasis. HPV status was not statistically predictive of patient outcome or CSCM expression; however, p16ink4a remains a potential marker in HNSCC Further in vitro studies with ALDH1 and p16ink4a should be performed to evaluate the expression of ALDH1 and HPV in cell culture and to clarify the role of ALDH1 as a marker for increased invasiveness of OSCC cells.