Search

Abstract Non-Hodgkin Lymphoma (NHL) is a neoplasm associated with a group of malignancies called AIDs-Defining Malignancies (ADMs) in Human-Immunodeficiency Virus (HIV) -patients. Similar to the case of NHL in Latin America, particularly in Peru, the amount of research done on others ADMs is limited, especially in the case of Kaposi’s Sarcoma (KS). Prior investigations have talked about the great potential risk that represents this illness in latin american population, but topics as prognosis factors are yet to be well defined. In this letter, we address the importance of investigation in this area and include previously reported data that may enlighten the current national standpoint.

Abstract Background Women in Africa are experiencing a rising burden of endometrial cancer. Research and investment to improve treatment and outcomes are critically needed. We systematically reviewed and characterized endometrial cancer-related research within a clinically relevant context to help organize and assess existing endometrial cancer research in Africa. Methods According to PRISMA guidelines, we searched online databases for published endometrial cancer articles from African countries from January 1, 2011, to July 20, 2021. Based on our inclusion and exclusion criteria, independent reviewers documented the study design, country/region, human development index, focus of research, type of interventions performed, and histologic and molecular type to illustrate the breadth of research coverage in each region. Results A total of 18 research articles were included. With an average Human Development Index (HDI) in Africa of 0.536, the average HDI of the represented countries in this study was 0.709. The majority (88.9%) of prospective endometrial cancer research articles in Africa were from North Africa, with Egypt encompassing 83.3% of the papers. Most of these studies focused on endometrial cancer diagnosis. Research on the treatment of endometrial cancer is still emerging (33% of papers). Of all included articles, only 11.1% represented Sub-Saharan Africa, where the majority population of black Africans reside. Conclusions Endometrial cancer research in Africa is extremely limited, with the majority being concentrated in African countries with higher HDIs. As the incidence of endometrial cancer rises in Sub-Saharan Africa, there is a pressing need for more prospective clinical research to tackle the growing disease burden and improve outcomes.

Abstract Background There is an increase in number of Human Papillomavirus related head and neck squamous cell carcinoma (HPV-related HNSCC) High risk HPV(HR-HPV) types can be cleared by an infected person, however, some can persist and develop HN cancer. There is a broad knowledge gap regarding HPV and related cancers. Main text The aim of this review is to assess existing published knowledge on oral-genital HPV transmission, concordance of HPV genotypes and risk of oral or/and genital lesions among spouses/partners of patients diagnosed with HPV-related HNSCC, identify gaps in the current research and highlight areas that requires further inquiry. Method Database like Pub med, Google Scholar, Scopus, Puplon, Wiley online library were used for search strategy. Published papers on transmission, concordance of HPV genotypes and genital lesions among spouses/partners of patients diagnosed with HPV-related HNSCC were included. Papers published from January1,2000 to October 31, 2022 were included. The published papers included are 8 Case reports, 2 cross-sectional studies, 3 Cohort studies and 2 systematic reviews. Results A total of 2125 citations were retrieved from the five sources. 15papers were included. Case reports reported concurrent HPV-related oropharyngeal, tonsillar, unspecified HNSCC, laryngeal and nasopharyngeal carcinoma among couples. The two cross-sectional studies were done. Almost all the tumors taken from patients with HPV-related oropharyngeal carcinoma (HPV-related OPC) and their spouses were positive for identical HPV 16 type. The three cohort studies showed an increase risk of upper aero-digestive tract cancer among male spouses of females with cervical cancer. Two systematic reviews reviewed literature studies which evaluated concurrent cases of HPV-related Oropharyngeal cancers. Examination of these papers showed that the majority of the studies suggested that there is HPV transmission, concordance and risk of HNSCC cancer among spouses with HPV-related oral-genital cancer. No studies evaluated the risk of developing genital cancer in spouses of patients with HNSCC. Conclusion The findings of this review highlighted big need of further research on oral-genital HPV infection among spouses of patients diagnosed with HPV-related HNSCC. Studies are needed to evaluate the risk of getting genital and upper aero-digestive tract HPV-related cancer among spouses with HPV-related HNC.

Abstract Objective Intestinal protozoa Blastocystis hominis and Cryptosporidium spp. are two influential factors in intestinal complications and malignancies. In present study, we estimated the pooled prevalence and odds ratio (OR) of the two parasites in colorectal cancer (CRC) patients and their possible association with the deadly disease. Method Our systematic search was conducted for published researches between January 1, 2000 and April 30, 2022 by using four international databases include Scopus, PubMed, and Web of Science as well as Google scholar search engine. The random- and fixed-effects models were used to estimate the pooled prevalence, OR, and 95% confidence interval (CI) by comprehensive meta-analysis (V2.2, Bio stat) software. Inclusion and exclusion criteria were applied. Results Thirteen papers (seven case–control and six cross-sectional studies) for B. hominis/CRC and six papers (two case–control and four cross-sectional studies) for Cryptosporidium spp./CRC were eligible to include in data synthesis. Pooled prevalence of B. hominis and Cryptosporidium spp. in CRC patients was calculated to be 26.8% (95% CI 19.4–35.7%) and 12.7% (95% CI 6.8–22.5%), respectively. Based on case–control studies, significant difference was found between case and controls in both protozoa (B. hominis OR 2.10; 95% CI 1.39–3.18% vs. Cryptosporidium spp. OR 5.06; 95% CI 1.8–13.6%). Considering the Blastocystis subtypes, ST1 (5/6; 83.33% studies) and ST3 (5/6; 83.33% studies) had the highest number of reports in CRC patients. Regarding the Cryptosporidium species, only C. parvum and C. hominis were reported. Conclusion Given the significant prevalence of both parasites in CRC patients and their statistically significant association, there is a need to pay more attention to these two intestinal parasites in under treatment patients.

Abstract Cervical cancer (CC) is a preventable disease and treatable cancer. Most of the new cases and deaths from CC occur in Low- and Middle-Income Countries (LMICs) due to cultural and systematic barriers leading to low CC screening uptake. In recent years, self-sampling has been proposed as a method to increase CC screening uptake and is slowly being implemented into screening programmes worldwide. Simultaneously, DNA methylation has been proposed as a novel biomarker that could be used for the triage of self-collected samples that test positive for high-risk types of Human Papillomavirus (HPV). In this paper, we conducted a literature review of studies assessing the efficacy of DNA methylation markers to detect Cervical Intraepithelial Neoplasia (CIN) in self-collected cervicovaginal swabs or urine (2019–2024). Our review showed that, of the available data, DNA methylation together with self-sampling could perform as well as cytology in the detection of CIN as well as improve uptake of CC screening and reduce loss to follow up, especially in LMICs. However, more data is still needed to understand which methylation tests are most efficacious. Future studies should assess the full potential of DNA methylation and self-sampling in large, diverse screening cohorts.

Abstract Infectious Agents and Cancer journal has recently launched a new collection of papers about “Point-of-Care (POC) for HPV-related genital cancers” putting together some interesting works on the accuracy of HPV tests for screening. This editorial initiative gave us the opportunity to reflect on the relations between accuracy measures, prevalence and characteristics of the tested population in the case of HPV-based screening. In screening test evaluation, we look at the clinical accuracy of the test as an intrinsic characteristic of the assay, which interacts with the characteristics of the population, the result being the screening performance. In the case of HPV testing, the clinical accuracy should be conceptualized in two steps, the analytical accuracy of the assay for HPV infection and the biological link between HPV infection and the target disease, i.e. the high-grade cervical intraepithelial neoplasia (hgCIN). This approach highlights that just a few false positive cases result from a lack of analytical specificity while most derive from women who have the infection but it did not progress to hgCIN. In addition, increasing prevalence of hgCIN results in relevant increases of PPV only if due or associated with exposures which increase the progression from infection to hgCIN or the duration of the latter; while an increase due to a higher prevalence of HPV infection would only marginally affect PPV. This approach may help in modelling the performance of HPV-based cervical screening.

Abstract Background This paper offers an assessment of diagnostic tools in the evaluation of Intrahepatic Cholangiocarcinoma (ICC). Methods Several electronic datasets were analysed to search papers on morphological and functional evaluation in ICC patients. Papers published in English language has been scheduled from January 2010 to December 2021. Results We found that 88 clinical studies satisfied our research criteria. Several functional parameters and morphological elements allow a truthful ICC diagnosis. The contrast medium evaluation, during the different phases of contrast studies, support the recognition of several distinctive features of ICC. The imaging tool to employed and the type of contrast medium in magnetic resonance imaging, extracellular or hepatobiliary, should change considering patient, departement, and regional features. Also, Radiomics is an emerging area in the evaluation of ICCs. Post treatment studies are required to evaluate the efficacy and the safety of therapies so as the patient surveillance. Conclusions Several morphological and functional data obtained during Imaging studies allow a truthful ICC diagnosis.

Abstract Background Recent articles have explored the effect of worms on cancer cells. This review focused on various cell cultures employed to understand which cells are more commonly and less utilized. Methods The present review analyzed studies published between 2013 and 2023 to obtain information about different cell cultures used in cancer studies involving helminths. Databases such as PubMed, Google Scholar, HINARI, and the Cochrane Library were searched. Results This search yielded 130 records, but 97 papers were excluded because they were either irrelevant to the research topic (n = 72) or contradicted the research idea (n = 25).The remaining twenty-one articles focused on different types of worms, such as Echinococcus granulosus, Clonorchis sinensis, Opisthorchis felineus, Opisthorchis viverrini, Trichinella spiralis, Toxocara canis, and Heligmosomoides polygyrus. Conclusion Due to the presence of numerous antigens, parasites at different growth stages can impact various cells through unknown mechanisms. Given the high diversity of antigens and their effects, artificial intelligence can assist in predicting initial outcomes for future studies.

Abstract This paper introduces two cases of multiple myeloma, COVID-19 infection during autologous stem cell transplantation, the treatment process, and different results of the two patients, which provides a reference for how to carry out ASCT safely during the COVID-19 normalization stage.

Abstract Background Patients with colorectal cancer (CRC) are more likely to develop severe course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and experience increased risk of mortality compared to SARS-CoV-2 patients without CRC. Objectives To estimate the prevalence of SARS-CoV-2 infection in CRC patients and analyse the demographic parameters, clinical characteristics and treatment outcomes in CRC patients with COVID-19 illness. Methods For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature for studies on the incidence of SARS-CoV-2 infection in CRC patients, published from December 1, 2019 to December 31, 2021, with English language restriction. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). Sub-group analyses were performed to minimize heterogeneity. Binary logistic regression model was used to explore the effect of various demographic and clinical characteristics on patient’s final treatment outcome (survival or death). Results Of the 472 papers that were identified, 69 articles were included in the systematic review and meta-analysis (41 cohort, 16 case-report, 9 case-series, 2 cross-sectional, and 1 case-control studies). Studies involving 3362 CRC patients with confirmed SARS-CoV-2 (all patients were adults) were analyzed. The overall pooled proportions of CRC patients who had laboratory-confirmed community-acquired and hospital-acquired SARS-CoV-2 infections were 8.1% (95% CI 6.1 to 10.1, n = 1308, 24 studies, I 2 98%, p = 0.66), and 1.5% (95% CI 1.1 to 1.9, n = 472, 27 studies, I 2 94%, p

Abstract Objective To verify the association of high-risk human papillomavirus (hrHPV) viral load reflected by cycle threshold (Ct) values from HPV testing on Cobas4800 assay with the histologic grades of cervical lesions via analysis on the combined data from two cervical cancer screening trials and to explore the referability of Ct values in management of the abnormalities from cervical cancer primary screening. Methods We analyzed the data from Chinese Multi-Center Screening Trial (CHMUST) and BUJI Cervical Cancer Screening Study Project (BUJI Study). All data to be analyzed in this paper were related to provider-collected samples. One-way ANOVA was performed to compare the Ct values among different histological groups, and Kendall’s tau-b correlation was applied to examine the association between Ct values and cervical lesion grades. The stepwise incidence of CIN2+ and CIN3+ in every 100 HPV positive individuals were calculated according to the descending of the genotype specific Ct values. The highest Ct values related to CIN3+ incidence rate 4% (or 25%) were used as the cutoffs to distinguish low-Ct value cases from the high-Ct value ones. Results A total of 1376 women in CHUMUST and BUJI Study who were aged 30–59 and positive of hrHPV for provider-collected samples on Cobas4800 with complete data in terms of the relevant Ct values (CtV) and the histological diagnosis were included for analysis. Our data showed significant difference among different histological grades of cervical lesions in the CtV of hrHPV, HPV16-plus (positive of HPV16 only or HPV16 plus 18 and/or pooled 12-HPV), and pooled 12-HPV (P 0.05). The CIN2+ or CIN3+ incidence per 100 positives significantly increased corresponding to the descending of the CtV of hrHPV, HPV16-plus and pooled 12-HPV. Compared with high-CtV groups (CtV > 33.2 for hrHPV, CtV > 29.6 for pooled 12-HPV), the relevant risks (RRs) of CIN2+ for hrHPV and pooled 12-HPV positive groups with low-CtV (CtV ≤ 33.2 and ≤ 29.6, respectively) were 3.2 (95%CI 2.18–4.80) and 2.3 (95%CI 1.50–3.45). Similarly, the RRs of CIN3+ for hrHPV and pooled 12-HPV positive groups with low-CtV were 6.5 (95%CI 2.83–14.80) and 2.7 (95%CI 1.15–6.39), respectively. The RRs of CIN2+ for medium- (30.3 37.4) groups, and the CIN3+ incidence in low-CtV value group was nine-fold higher of that in medium-CtV ones [RRs, 9.0 (95%CI 2.89–28.10)]. In comparing with the algorithms of “HPV16-plus/18-plus + cytology ≥ ASCUS for pooled 12-HPV”, triage algorithm “HPV16-plus/18-plus + Ct value ≤ 33.2 for pooled 12-HPV” could achieve a comparable sensitivity of 93.2%. Conclusion HPV viral loads reflected by Ct values for hrHPV, HPV16-plus and pooled 12-HPV from Cobas4800 HPV testing were directly associated with the severity of cervical lesions. A lower HPV genotype-specific Ct value prompted a significantly high CIN3+ risk of 4% or higher in women positive of hrHPV, HPV16-plus or pooled 12-HPV, indicating that HPV viral load reflected by Ct values on Cobas4800 may be a promising risk indicator in management of abnormalities from primary cervical cancer screening.

Abstract Background To date, no paper reports cases of lymphangitis after COVID 19 vaccination. We present a case of lymphangitis after vaccination from COVID 19, in a patient with colorectal liver metastases. Methods We described the case of a 56-year-old woman with history of a surgical resection of colorectal cancer and liver metastases, without any kind of drug therapy for about a month. In addition, a recent administration (2 days ago) of Spikevax (mRNA-1273, Moderna vaccine), as a booster dose, on the right arm was reported. Results The magnetic resonance (MR) examination showed the effects of the previous surgical resection and five new hepatic metastases, located in the VIII, VI, V, IV and II hepatic segments. As an accessory finding the presence of lymphadenopathy in the axillary area and lymphangitis of the right breast and chest were identified. The computed tomography scan performed a week earlier, and re-evaluated in light of the MR data, did not identify the presence of lymphadenopathy in the axillary area and lymphangitis signs. Conclusions Lymphangitis could occur after COVID 19 vaccine and it is important to know this data to avoid alarmism in patients and clinicians and economic waste linked to the execution of various radiological investigations for the search for a tumour that probably does not exist. Trial registration: Not applicable.

Abstract Background Earlier I hypothesized that hereditary tumors might participate in the evolution of multicellular organisms. I formulated the hypothesis of evolution by tumor neofunctionalization, which suggested that the evolutionary role of hereditary tumors might consist in supplying evolving multicellular organisms with extra cell masses for the expression of evolutionarily novel genes and the origin of new cell types, tissues, and organs. A new theory—the carcino-evo-devo theory—has been developed based on this hypothesis. Main text My lab has confirmed several non-trivial predictions of this theory. Another non-trivial prediction is that evolutionarily new organs if they originated from hereditary tumors or tumor-like structures, should recapitulate some tumor features in their development. This paper reviews the tumor-like features of evolutionarily novel organs. It turns out that evolutionarily new organs such as the eutherian placenta, mammary gland, prostate, the infantile human brain, and hoods of goldfishes indeed have many features of tumors. I suggested calling normal organs, which have many tumor features, the tumor-like organs. Conclusion Tumor-like organs might originate from hereditary atypical tumor organs and represent the part of carcino-evo-devo relationships, i.e., coevolution of normal and neoplastic development. During subsequent evolution, tumor-like organs may lose the features of tumors and the high incidence of cancer and become normal organs without (or with almost no) tumor features.

Abstract Background The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. Methods In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profiling (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by multiple immunohistochemistry (IHC) and multispectral immunofluorescence (IF), we investigated the TME of additional series of 40 BL cases to evaluate the role of the Programmed Death-1 and Programmed Death Ligand-1 (PD-1/PD-L1) immune checkpoint axis. Results Our results indicate that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tumour cells, highlighting a subgroup of BL cases characterized by a non-canonical latency program of EBV with an activated PD-L1 pathway. Conclusion In conclusion, our study analysed the TME in BL and identified a tolerogenic immune signature highlighting new potential therapeutic targets.

Abstract Earlier we suggested a new hypothesis of the possible evolutionary role of hereditary tumors (Kozlov, Evolution by tumor Neofunctionalization, 2014), and described a new class of genes – tumor specifically expressed, evolutionarily novel (TSEEN) genes - that are predicted by this hypothesis (Kozlov, Infect Agents Cancer 11:34, 2016). In this paper we studied evolutionarily novel genes expressed in fish tumors after regression, as a model of evolving organs. As evolutionarily novel genes may not yet have organismal functions, we studied the acquisition of new gene functions by comparing fish evolutionarily novel genes with their human orthologs. We found that many genes involved in development of progressive traits in humans (lung, mammary gland, placenta, ventricular septum, etc.) originated in fish and are expressed in fish tumors and tumors after regression. These findings support a possible evolutionary role of hereditary tumors, and in particular the hypothesis of evolution by tumor neofunctionalization. Research highlights Earlier we described a new class of genes that are tumor-specifically expressed and evolutionarily novel (TSEEN). As the functions of TSEEN genes are often uncertain, we decided to study TSEEN genes of fishes so that we could trace the appearance of their new functions in higher vertebrates. We found that many human genes which are involved in development of progressive traits (placenta development, mammary gland and lung development etc.,) originated in fishes and are expressed in fish tumors.

Abstract Oesophageal carcinoma (OC) is highly prevalent in Western Kenya especially among the members of the Kalenjin community who reside in the Northern and Southern areas of the Rift Valley. Previous authors have suggested potential association of environmental and genetic risk factors with this high prevalence. The environmental factors that have been suggested include contamination of food by mycotoxins and/or pesticides, consumption of traditional alcohol (locally referred to “Busaa” and “Chan’gaa”), use of fermented milk (“Mursik”), poor diet, tobacco use and genetic predisposition. The aim of this paper is to critically examine the potential contribution of each of the factors that have been postulated to be associated with the high prevalence of the disease in order to establish the most likely cause. We have done this by analyzing the trends, characteristics and behaviours that are specifically unique in the region, and corroborated this with the available literature. From our findings, the most plausible cause of the high incidence of OC among the Kalenjin community is mycotoxins, particularly fumonisins from the food chain resulting from poor handling of cereals; particularly maize combined with traditional alcohol laced with the toxins interacting synergistically with other high-risk factors such as dietary deficiencies associated alcoholism and viral infections, especially HPV. Urgent mitigating strategies should be developed in order to minimize the levels of mycotoxins in the food chain.

Abstract Background Literature data suggest that multi-parametric Magnetic Resonance Imaging (MRI), including morphologic T2-weigthed images (T2-MRI) and functional approaches such as Dynamic Contrast Enhanced-MRI (DCE-MRI), Diffusion Weighted Imaging (DWI) and Magnetic Resonance Spectroscopic Imaging (MRSI), give an added value in the prostate cancer localization and local staging. Methods We performed a systematic review of literature about the role and the potentiality of morphological and functional MRI in prostate cancer, also in a multimodal / multiparametric approach, and we reported the diagnostic accuracy results for different imaging modalities and for different MR coil settings: endorectal coil (ERC) and phased array coil (PAC). Forest plots and receiver operating characteristic curves were performed. Risk of bias and the applicability at study level were calculated. Results Thirty three papers were identified for the systematic review. Sensitivity and specificity values were, respectively, for T2-MRI of 75% and of 60%, for DCE-MRI of 80% and of 72%, for MRSI of 89% and of 69%, for combined T2-MRI and DCE-MRI of 87% and of 46%, for combined T2-MRI and MRSI of 79% and of 57%, for combined T2-MRI, DWI and DCE-MRI of 81% and of 84%, and for combined MRSI and DCE-MRI of 83% and of 83%. For MRI studies performed with ERC we obtained a pooled sensitivity and specificity of 81% and of 66% while the pooled values for MRI studies performed with PAC were of 78% and of 64%, respectively (p>0.05 at McNemar test). No studies were excluded from the analysis based on the quality assessment. Conclusions ERC use yielded no additional benefit in terms of prostate cancer detection accuracy compared to multi-channel PAC use (71% versus 68%) while the use of additional functional imaging techniques (DCE-MRI, DWI and MRSI) in a multiparametric MRI protocol improves the accuracy of prostate cancer detection allowing both the early cure and the guidance of biopsy.

An amendment to this paper has been published and can be accessed via the original article.

An amendment to this paper has been published and can be accessed via the original article.

An amendment to this paper has been published and can be accessed via the original article.

Abstract The eruption of Kaposi sarcoma (KS) and aggressive non-Hodgkin lymphoma (NHL) in young homosexual men in 1981 in the West heralded the onset of the human immunodeficiency virus (HIV) infection epidemic, which remains one of the biggest challenges to global public health and science ever. Because KS and NHL were increased >10,000 and 50-600 times, respectively, with HIV, they were designated AIDS defining cancers (ADC). Cervical cancer (CC), increased 5-10 times was also designated as an ADC. A few other cancers are elevated with HIV, including Hodgkin lymphoma (10 times), anal cancer (15-30 times), and lung cancer (4 times) are designated as non-AIDS defining cancers (NADCs). Since 1996 when combination antiretroviral therapy (cART) became widely available in the West, dramatic decreases in HIV mortality have been observed and substantial decrease in the incidence of ADCs. Coincidentally, the burden of NADCs has increased as people with HIV age with chronic HIV infection. The impact of HIV infection on cancer in sub-Saharan Africa, where two thirds of the epidemic is concentrated, remains poorly understood. The few studies conducted indicate that risks for ADCs are also increased, but quantitatively less so than in the West. The risks for many cancers with established viral associations, including liver and nasopharynx, which are found in Africa, do not appear to be increased. These data are limited because of competing mortality, and cancer is under diagnosed, pathological confirmation is rare, and cancer registration not widely practiced. The expansion of access to life-extending cART in sub-Saharan Africa, through programs such as the Global Fund for AIDS, Malaria, and Tuberculosis and the US President's Emergency Program for AIDS Relief (PEPFAR), is leading to dramatic lengthening of life of HIV patients, which will likely influence the spectrum and burden of cancer in patients with HIV. In this paper, we review current literature and explore merits for integrating cancer research in established HIV programs to obtain timely data about the incidence and burden of cancer in HIV-infected persons in Africa.

Abstract Cancer statistics report an increased incidence of OSCC and OPSCC around the world. Though improvements in screening and early diagnosis have dramatically reduced the incidence of this neoplasm in recent years, the 5-year-disease-free survival, is still poor, specially for oropharyngeal cancer, despite the great scientific and financial efforts. Recently, several papers showed that HPV may be involved at least in the pathogenesis of a subgroup of oral and cervical SCC, leading to distinct molecular characteristics compared with HPV-negative ones. Nevertheless, OPSCCs associated with HPV infection seem to show a better prognosis and affect younger patients (< 40 yrs.), especially females. Therefore, there is the need to properly assess oropharyngeal SCC subgroups: 1) not HPV associated/classic oral SCC: less responsive to anticancer drugs: needs novel post-surgical treatment; 2) HPV associated/oral SCC: needs several management options and suitable "target" therapy against the virus, and/or immune-stimulating therapy. Further issues are: 1) the disclosure of putative targets for more efficient molecular therapy, which may work as cervical cancer post-surgical treatment, in anticipation of the effects of "global prevention" performed by WHO anti-HPV vaccination programs; 2) careful identification of precancerous lesions in both sites; dysplasia is currently treated by excisional or ablative procedures, which don't consider the concept of field carcinogenesis. In fact, it is probable that near or far from an excised precancerous lesion new foci of cell transformation may exist, which are not yet macroscopically evident, but, if detected, would put the patient into a high risk subgroup. Comparing findings reported in the recent literature, the data of this state of the art about HPV might add useful informations concerning oropharyngeal carcinogenesis. Moreover, our review would be useful in order to define novel perspectives of treatment choice for Head & Neck cancer patients, by combining well known chemotherapeutical drugs with new molecular "target" therapy.

Abstract Background Human papillomavirus (HPV) E6/E7 type-specific oncogenes are required for cervical carcinogenesis. Current PCR protocols for genotyping high-risk HPV in cervical screening are not standardized and usually use consensus primers targeting HPV capsid genes, which are often deleted in neoplasia. PCR fragments are detected using specialized equipment and extra steps, including probe hybridization or primer extension. In published papers, analytical sensitivity is typically compared with a different protocol on the same sample set. A single-tube multiplex PCR containing type-specific primers was developed to target the E6/E7 genes of two low-risk and 19 high-risk genotypes (HPV6, 11 and 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73 and 82) and the resulting short fragments were directly genotyped by high-resolution fluorescence capillary electrophoresis. Results The method was validated using long oligonucleotide templates, plasmid clones and 207 clinical samples of DNA from liquid-based cytology, fresh and formalin-fixed specimens and FTA Microcards® imprinted with cut tumor surfaces, swabbed cervical cancers or ejected aspirates from nodal metastases of head and neck carcinomas. Between one and five long oligonucleotide targets per sample were detected without false calls. Each of the 21 genotypes was detected in the clinical sample set with up to five types simultaneously detected in individual specimens. All 101 significant cervical neoplasias (CIN 2 and above), except one adenocarcinoma, contained E6/E7 genes. The resulting genotype distribution accorded with the national pattern with HPV16 and 18 accounting for 69% of tumors. Rare HPV types 70 and 73 were present as the sole genotype in one carcinoma each. One cervical SCC contained DNA from HPV6 and 11 only. Six of twelve oropharyngeal cancer metastases and three neck metastases of unknown origin bore E6/E7 DNA; all but one were HPV16. One neck aspirate contained atypical squames with HPV26. Analytical sensitivity in dilute plasmid mixes was variable. Conclusions A primer-rich PCR readily detects the E6/E7 oncogenes of 21 HPV types in cellular and fixed tissue specimens. The method is straightforward, robust and reproducible and avoids post-PCR enzymatic and hybridization steps while detecting HPV with high clinical sensitivity in significant HPV-related neoplasia regardless of specimen type.

Abstract Objective To provide guidelines for health-care providers on strategies for cervical cancer prevention based on HPV testing and anti-HPV vaccination. Outcomes Overall efficacy of different preventive strategies, assessing reduction in the incidence of invasive cervical cancer and precancerous lesions. Evidence Medline and the Cochrane Database were searched for articles in English on subjects related to HPVs, HPV diagnosis, HPV anogenital lesions, cervical cancer, HPV testing, and HPV vaccines, in order to elaborate an up-dated document. Relevant Italian Government publications and position papers from appropriate health and family planning organizations were also reviewed. Values The quality of the evidence and ranking of recommendations for practice were rated using criteria defined by SIV, which were adapted from the Canadian Task Force on Preventive Health Care.

Abstract Background The phenomenon of hormesis, whereby small amounts of seemingly harmful or stressful agents can be beneficial for the health and lifespan of laboratory animals has been reported in literature. In particular, there is accumulating evidence that daily brief cold stress can increase both numbers and activity of peripheral cytotoxic T lymphocytes and natural killer cells, the major effectors of adaptive and innate tumor immunity, respectively. This type of regimen (for 8 days) has been shown to improve survival of mice infected with intracellular parasite Toxoplasma gondii, which would also be consistent with enhanced cell-mediated immunity. Presentation of the hypothesis This paper hypothesizes that brief cold-water stress repeated daily over many months could enhance anti-tumor immunity and improve survival rate of a non-lymphoid cancer. The possible mechanism of the non-specific stimulation of cellular immunity by repeated cold stress appears to involve transient activation of the sympathetic nervous system, hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes, as described in more detail in the text. Daily moderate cold hydrotherapy is known to reduce pain and does not appear to have noticeable adverse effects on normal test subjects, although some studies have shown that it can cause transient arrhythmias in patients with heart problems and can also inhibit humoral immunity. Sudden immersion in ice-cold water can cause transient pulmonary edema and increase permeability of the blood-brain barrier, thereby increasing mortality of neurovirulent infections. Testing the hypothesis The proposed procedure is an adapted cold swim (5–7 minutes at 20 degrees Celsius, includes gradual adaptation) to be tested on a mouse tumor model. Mortality, tumor size, and measurements of cellular immunity (numbers and activity of peripheral CD8+ T lymphocytes and natural killer cells) of the cold-exposed group would be compared to those of control groups (warm swim and no treatment). Cold-water stress would be administered twice a day for the duration of several months. Implications of the hypothesis If the hypothesis is supported by empirical studies and the method is shown to be safe, this could lead to the development of an adjunctive immunotherapy for some (non-lymphoid) cancers, including those caused by viral infections.

Abstract Background Few reports of the utilization of an accurate, cost-effective means for measuring HPV oncogene transcripts have been published. Several papers have reported the use of relative quantitation or more expensive Taqman methods. Here, we report a method of absolute quantitative real-time PCR utilizing SYBR-green fluorescence for the measurement of HPV E7 expression in cervical cytobrush specimens. Results The construction of a standard curve based on the serial dilution of an E7-containing plasmid was the key for being able to accurately compare measurements between cervical samples. The assay was highly reproducible with an overall coefficient of variation of 10.4%. Conclusion The use of highly reproducible and accurate SYBR-based real-time polymerase chain reaction (PCR) assays instead of performing Taqman-type assays allows low-cost, high-throughput analysis of viral mRNA expression. The development of such assays will help in refining the current screening programs for HPV-related carcinomas.