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Cancers of the upper aerodigestive tract [(UADT): oral cavity, pharynx, larynx and oesophagus] have high incidence rates in some parts of South America. Alterations in the TP53 gene are common in these cancers. In our study, we have estimated the prevalence and patterns of TP53 mutations (exons 4–10) in 236 UADT tumours from South America in relation to lifestyle risk factors, such as tobacco smoking and alcohol drinking. Moreover, we have conducted a pilot study of EGFR mutations (exons 18–21) in 45 tumours from the same population. TP53 mutation prevalence was high: 59% of tumours were found to carry mutant TP53. We found an association between TP53 mutations and tobacco smoking and alcohol drinking. The mutation rate increased from 38% in never-smokers to 66% in current smokers (P-value for trend = 0.09). G:C>T:A transversions were found only in smokers (15%). Alcohol drinkers carried more G:C>A:T transitions (P = 0.08). Non-exposed individuals were more probable to carry G:C>A:T transitions at CpG sites (P = 0.01 for never-smokers and P < 0.001 for never-drinkers). EGFR mutations were found in 4% of cases. Inactivation of TP53 by mutations is a crucial molecular event in the UADT carcinogenesis and it is closely related to exposure to lifestyle risk factors. EGFR mutations do not appear to be a common event in UADT carcinogenesis in this population. [ABSTRACT FROM PUBLISHER]

SARS-CoV-2 has recently emerged, becoming a global threat, affecting directly all human beings owing to its morbidity and mortality and indirectly, due to the enormous economic and psychological impact produced by social isolation, the most effective measure so far, but unsustainable for a long period. The scientific effort to understand and control SARS-CoV-2 transmission and clinical impact has been huge, and important achievements are highlighted in this review. Diagnosis is central and is the first step in recognizing and fighting any infectious agent. Instrumental to that is the quality of the data, relying on serological and molecular surveys in addition to trustworthy clinical records. However, the fast spread of a virus adapted for human-to-human respiratory transmission raised a demand for millions of molecular tests that are simply not available. Several candidate drugs are under evaluation in clinical trials. Those with an already recognized safety profile are more auspicious, since, if proven effective, can cut several steps of production and phase 2 and 3 trials. More than one hundred vaccine prototypes are in different stages of development, however, safety and efficacy evaluations cannot be obviated, implicating, most optimistically, in at least months for us to have an effective immunization, the definite measure to allow a safe return to the pre-pandemic lifestyle. Science has never been more necessary and present in daily life. Relying on the best of human wit is the only way out to this pandemic, saving as many lives as possible.

The association between high-risk human papillomavirus (HPV) genotypes and p16 expression in indigenous women from the Xingu Indigenous Park, Brazil, was unknown. This study evaluated p16 expression in women with a histological diagnosis of cervical intraepithelial neoplasia (CIN) 3 or higher and correlated this expression with HPV genotypes to determine possible discrepancies in the expression of this marker. We evaluated 37 previously collected samples with different HPV genotypes and high-grade lesions diagnosed based on cytology, histology, and colposcopy. Immunohistochemical analysis was performed using paraffin-embedded tissue sections and the CINtec® Histology Kit. p16 protein expression was investigated by immunostaining with an anti-p16 antibody. HPV genotyping was performed by reverse hybridization. The age of the study population ranged from 22-75 years (43.81 ± 15.89 years) and parity ranged from 1-11 (5.92 ± 2.58). Thirteen different HPV genotypes were found using the INNO-LiPA kit. Single and multiple infections by HPV were found with prevalence of single infections (P = 0.029). Comparison between HPV genotype and simple or multiple infections was highly significant; it was observed more HPV 52 followed by HPV 16 in single infections (P < 0.001). p16 expression was predominantly diffuse, which was observed in 91.7% of lesions, whereas 8.3% were focal (P < 0.001). HPV 52, HPV 16 and 31 were the most prevalent HPV types in high-grade CIN in these indigenous women. Diffuse p16 expression in high-grade CIN was not influenced by the viral genotype; however, more studies are necessary to further our understanding of this restricted group.

HIV and human papillomavirus (HPV) coinfection is increasing, especially in the anal canal (AC) and cervico-vaginal regions. We identified anal epithelium abnormalities related to high-risk HPV (HR-HPV) lesions in the lower genital tracts (LGTs) of HIV-positive women, described the HPV genotypes identified, and assessed the expression of E6/E7 oncogenes in coinfected patients. Ninety-eight women were enrolled in groups combining HIV status and presence or absence of HPV in the LGT. Anal and cervical smears were collected for cytology and HR-HPV assays using Cobas(®) and/or PapilloCheck(®). Samples with highly oncogenic HPV genotypes were confirmed by NucliSENS EasyQ(®). Forty-two HIV-positive (25-52; mean age 39.5) and 56 HIV-negative (18-58; mean age 35.7) patients were included. E2 and C1 groups presented AC alterations (P = 0.002); altered images for high-resolution anoscopy were higher in E1 and C2 (P < 0.001). Of the 29 women with alterations, 41.38% were HIV-negative and 58.62% were HIV-positive (P < 0.001). HIV-positive patients accounted for 29% of the anal high-grade squamous intraepithelial lesions (P = 0.015). The Cobas(®) positive result frequency was higher in three AC groups than in the other groups. There was variation in the number of HPV types in the cervico-vaginal samples among the study groups (P < 0.001). Anal cytology and anoscopy showed more altered findings in HIV-positive patients with HPV in the LGT. HR-HPV anal infections by various genotypes are common and are associated with cervical infections in HIV-positive patients. E6/E7 expression is apparently more common in the AC of HIV-positive women.

The association of education, tobacco smoking, alcohol consumption, and interleukin-2 (IL-2 +114 and -384) and -6 (IL-6 -174) DNA polymorphisms with head and neck squamous cell carcinoma (HNSCC) was investigated in a cohort study of 445 subjects. IL-2 and IL-6 genotypes were determined by real-time PCR. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) of disease-specific survival according to anatomical sites of the head and neck. Mean age was 56 years and most patients were males (87.6%). Subjects with 5 or more years of schooling had better survival in larynx cancer. Smoking had no effect on HNSCC survival, but alcohol consumption had a statistically significant effect on larynx cancer. IL-2 gene +114 G/T (HR = 0.52; 95%CI = 0.15-1.81) and T/T (HR = 0.22; 95%CI = 0.02-3.19) genotypes were associated with better survival in hypopharynx cancer. IL-2 +114 G/T was a predictor of poor survival in oral cavity/oropharynx cancer and larynx cancer (HR = 1.32; 95%CI = 0.61-2.85). IL-2 -384 G/T was associated with better survival in oral cavity/oropharynx cancer (HR = 0.80; 95%CI = 0.45-1.42) and hypopharynx cancer (HR = 0.68; 95%CI = 0.21-2.20), but an inverse relationship was observed for larynx cancer. IL-6 -174 G/C was associated with better survival in hypopharynx cancer (HR = 0.68; 95%CI = 0.26-1.78) and larynx cancer (HR = 0.93; 95%CI = 0.42-2.07), and C/C reduced mortality in larynx cancer. In general, our results are similar to previous reports on the value of education, smoking, alcohol consumption, and IL-2 and IL-6 genetic polymorphisms for the prognosis of HNSCC, but the risks due to these variables are small and estimates imprecise.

Our study aimed at evaluating the presence of human papillomavirus (HPV) DNA in a series of 84 paraffin-embedded (PET) penile carcinomas. We have also investigated the presence of p53 mutations in these tumors by immunohistochemistry (IHC), single-stranded conformational polymorphism (SSCP) and DNA sequencing. Tissues were submitted to amplification of a 268 bp fragment from the beta-globin gene and a fragment of the E6 gene of HPV types 6, 11, 16 and 18. Twenty samples (18 fixed in Bouin's solution and 2 in buffered formalin) were found inadequate and were excluded from the analysis. In the remaining 64 tumors, HPV DNA was found in 26% of the samples. The prevalence of HPV in fresh samples of the same tumors was 56%. The most prevalent type was HPV 16 in both fresh samples and PET. Isotopic in situ hybridization was performed in all PET samples, but only 2 cases were positive, 1 for HPV 16 and 1 for HPV 18. Immunohistochemistry with anti-p53 pAb 1801 antibody showed a positive nuclear reaction over more than 5% of tumor cells in 26% of the cases. SSCP of exons 5-8 of the p53 gene was performed on 9 HPV-positive and 12 HPV-negative specimens. Abnormal mobility was found in 26% of the tumors, of which 2 were HPV-positive and 5 HPV-negative. Point mutations were detected in p53 exons 6 (1 case), 7 (1 case) and 8 (5 cases), showing that high-risk type HPVs and mutated p53 may coexist in these tumors. Our data indicate that a subset of penile carcinomas are etiologically related to HPV and that an overlapping subset may arise from mutational events in the p53 gene.

A new PCR-based technique, low stringency single specific primer-PCR (LSSP-PCR), has been adapted to produce gene signatures capable of distinguishing human papillomaviruses (HPVs) in clinical specimens. This approach potentially offers a sensitive, inexpensive and high-throughput methodology for precise clinical diagnosis of HPV infections.

Monoclonal antibodies against cell surface receptors can be useful for the study of structural and biochemical features involved in protein interactions underlying platelet adhesion and aggregation. We report here the characterization of a monoclonal antibody, IID510g52 (hereafter referred to as IID5), which has been selected based on its specific binding properties against the platelet membrane glycoprotein IIIa. Characterization of the reactive epitope, including evolutionary conservation and identification of related IID5 target antigens in tumor cells, suggest that the IID5 epitope is implicated in the ligand-binding function of integrin receptors. Indeed, we show that this MoAb acts as a potent inhibitor of platelet aggregation and cell adhesion. Taken together, these results indicate that such a monoclonal may be a strategic tool for better understanding multiple integrin-mediated adhesive reactions, as well as the determination of interacting recognition sites.

The authors have demonstrated the presence of human papillomavirus (HPV) types 6 and 11 in 10 of 13 (77%) juvenile laryngeal papillomatosis by in situ DNA hybridization using as probes the radiolabeled DNAs of HPVs 6, 11, 16, and 18. Of six specimens from adult laryngeal papillomatosis assayed by the same technique, only 33% were positive. Immunohistochemistry to detect HPV capsid antigens performed on serial sections gave positive signals in 44% (8 of 18) of the specimens, all from juvenile lesions. These results were in agreement with in situ hybridization, except in two cases. When both series (juvenile and adult) were analysed by amplification of a 450-bp fragment corresponding to the L1 ORF of the HPV genomes directed by the polymerase chain reaction, the frequency of positive specimens rose to 100%. Our data agree with the concept that HPV is implicated in the etiology of laryngeal papillomatosis.

PFHR 9 is a murine teratocarcinoma-derived tumor which produces basement membrane components. Electron microscopy of the tumor cells disclosed a disorganization of the Golgi complex whose saccules, instead of being flattened, round up into 0.13 micron-wide spherical vesicles (SV). Their shape does not permit the normal stacking of parallel cisternae, and thus these SV become intermingled with transport vesicles (TV) which measure 44 nm in diameter. The cytoplasm of these tumor cells contains numerous multivesicular bodies (MVB) of varying size (ranging from 0.3 to 2.6 micron), which occupy 7% of the cellular volume. These MBV are packed with very many small vesicles similar in all aspects to the TV, and also contain a few larger vesicles which resemble the altered Golgi saccules (SV). Since these MVB display morphologic evidence for gradual lysis of their contents and strongly react with the cytochemical method for acid phosphatase, it is assumed that MVB are autophagic vacuoles which result from the accumulation of TV. This seems to be a unique example of a disease of the Golgi stack, with consequent accumulation and disposal of this material via autophagic vacuoles.