No association between HPV-status in tonsillar tissue and sexual behavior of the patients in a northern German population - Critical view of the link between HPV natural history and HPV-driven carcinogenesis.

HPV-infection in patients with HNSCC is reportedly correlated with sexual behavior, age, and tobacco/alcohol-consumption. HPV-infections of the oral cavity are regarded as sexually transmitted. Comparable data of patient populations outside the U.S. are sparse or missing. Questionnaires regarding sexual behavior, education tobacco- and alcohol-consumption, were given to 28 patients with tonsillar hyperplasia (H) and 128 patients with tonsillar carcinomas (CA), all with tissue-typed HPV-DNA-status performing PCR. Answers were correlated among groups and HPV-status. 106 questionnaires were analyzed. Comparisons between H- (n = 25) and CA- (n = 81) patients showed that CA-patients were older (61.1yrs ± 9.3) than H-patients (45.2yrs ± 11.9; p < 0.0001; Student's t-test); had a lower educational level (p = 0.0095); and lower number of sexual partners (p = 0.0222; Fisher's exact test). All groups showed a significant correlation between smoking and lack of HPV-DNA-positivity (p = 0.001). Further Fisher's exact tests and logistic regression analysis revealed in all 106 patients no significant correlations between tissue-HPV-status and the analyzed parameters. Despite the limited sample size, we were able to confirm the established correlation between smoking and tissue-HPV-status. The correlation between sexual behavior and HPV-infection was not confirmed. No consensus exists in the literature about the latter. Our data does not support the strict classification of oral HPV-infections and HPV-driven HNSCCs as STDs.

Influence of HPV-status on survival of patients with tonsillar carcinomas (TSCC) treated by CO2-laser surgery plus risk adapted therapy - A 10 year retrospective single centre study.

The positive prognostic value of HPV-infections in oropharyngeal squamous cell cancer (OSCC) patients has led to the initiation of prospective clinical trials testing the value of treatment de-escalation. It is unclear how to define patients potentially benefiting from de-escalated treatment, whether a positive smoking history impacts survival data and what kind of de-escalation might be best. Here, we investigate the effect of HPV-status, smoking habit and treatment design on overall survival (OS) and progression free survival (PFS) of 126 patients with tonsillar SCC (TSCC) who underwent CO2-laser-surgery and risk adapted adjuvant treatment. HPV-DNA-, HPV-mRNA-, and p16INK4A-expression were analysed and results were correlated to OS and PFS. Factors tested for prognostic value included HPV-status, p16INK4A-protein expression, therapy and smoking habit. Log rank test and p-values ≤0.05 defined significant differences between groups. The highest accuracy of data with highest significance in this study is given when the HPV-RNA-status is considered. Using p16INK4A-expression alone or in combination with HPV-DNA-status, would have misclassified 23 and 7 patients, respectively. Smoking fully abrogates the positive impact of HPV-infection in TSCC on survival. Non-smoking HPV-positive TSCC patients show 10-year OS of 100% and 90.9% PFS when treated with adjuvant RCT. The presented data show that high-precision HPV-detection methods are needed, specifically when treatment decisions are based on the results. Furthermore, smoking habit should be included in all studies and clinical trials testing HPV-associated survival. Adjuvant RCT especially for HPV-positive non-smokers may help to avoid distant failure.

Occurrence of neutrophil extracellular DNA traps (NETs) in pre-eclampsia: a link with elevated levels of cell-free DNA?

Manifest pre-eclampsia is associated with activation of peripheral neutrophils as well as elevations in maternal cell-free DNA. For this reason, we were very intrigued by recent reports indicating that activated circulatory neutrophils secrete nuclear DNA to generate extracellular DNA lattices, termed NETs (neutrophil extracellular traps). Our preliminary data indicate that placental syncytiotrophoblast microparticles, which are released in elevated amounts in pre-eclampsia, can induce NETs in isolated neutrophils. Furthermore, we found evidence for the increased presence of NETs directly in the intervillous space of pre-eclamptic placentae. Therefore, these newly discovered entities may be implicated in the underlying etiology of this disorder.

Organization and neural connections of the anterior optic tubercle in the brain of the locust, Schistocerca gregaria.

The anterior optic tubercle is a small neuropil in the insect brain and a major target of visual interneurons from the optic lobe. The functional role of the tubercle is poorly understood, but recent evidence from locusts points to a possible involvement in polarization vision. The present study examines the organization of the anterior optic tubercle in the locust Schistocerca gregaria and its connections with other brain areas. The tubercle of the locust consists of an upper and a lower subunit. Both units are connected in parallel with the medulla and lobula of the optic lobe, with the contralateral tubercle, and with the lateral accessory lobe in the median protocerebrum. Wide-field transmedullary neurons provide input from the medulla. Neurons with processes in the dorsal rim of the medulla, a relay station in the polarization vision pathway, project exclusively to the lower unit of the tubercle. Visual input from the lobula to the upper and lower unit originates from topographically distinct strata. The most prominent output target of the tubercle is the lateral accessory lobe in the median protocerebrum. Neurons from the upper unit project widely in the lateral accessory lobe, whereas neurons from the lower unit have focused projections confined to the median olive and to the lateral triangle. The two subunits of the anterior optic tubercle are, therefore, processing stages in two parallel visual pathways from the optic lobe to the median protocerebrum. Pathways via the lower unit of the tubercle appear to be involved in polarization vision.

Immunocytochemistry of histamine in the brain of the locust Schistocerca gregaria.

Histamine serves a neurotransmitter role in arthropod photoreceptor neurons, but is also present in a small number of interneurons throughout the nervous system. In search of a suitable model system for the analysis of histaminergic neurotransmission in insects, we mapped the distribution of histamine in the brain of the desert locust Schistocerca gregaria by immunocytochemistry. In the optic lobe, apparently all photoreceptor cells of the compound eye with projections to the lamina and medulla showed intense immunostaining. Photoreceptors of the dorsal rim area of the eye had particularly large fiber diameters and gave rise to uniform varicose immunostaining throughout dorsal rim areas of the lamina and medulla. In the locust midbrain 21 bilateral pairs of histamine-immunoreactive interneurons were found, and 13 of these were reconstructed in detail. While most neuropil areas contained a dense meshwork of immunoreactive processes, immunostaining in the antennal lobe and in the calyces of the mushroom body was sparse and no staining occurred in the pedunculus and lobes of the mushroom body, in the protocerebral bridge, and in the lower division of the central body. A prominent group of four immunostained neurons had large cell bodies near the median ocellar nerve root and descending axonal fibers. These neurons are probably identical to previously identified primary commissure pioneer neurons of the locust brain. The apparent lack in the desert locust of certain histamine-immunoreactive neurons which were reported in the migratory locust may be responsible for differences in the physiological role of histamine between both species.