In the county of Stockholm, between 1970 and 2002, we have previously reported a 3-fold parallel increase in the incidence of tonsillar squamous cell carcinoma (SCC) and the proportion of human papillomavirus (HPV) positive tonsillar SCC. Here, we have followed the above parameters in all patients (n 5 120) diagnosed with tonsillar SCC during [2003][2004][2005][2006][2007] in the same area, and also in correlation to our previous data. Ninety-eight pretreatment biopsies were available and presence of HPV DNA and HPV-16 E6 and E7 RNA were tested by polymerase chain reaction (

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Numerous reports have shown that the incidence for oropharyngeal cancer is increasing and that human papillomavirus (HPV) is a risk factor. However, few studies have investigated the specific subsites of the oropharynx. Following our previous research on tonsillar cancer, we assessed the increase in the incidence of base of tongue cancer and the prevalence of HPV in this disease. Between 1998 and 2007, 109 patients were diagnosed for base of tongue cancer in Stockholm county. Ninety‐five paraffin‐embedded diagnostic tumor biopsies from patients were obtained and tested for HPV, both by general HPV PCR and HPV‐16/HPV‐33 type‐specific PCR. Expression of HPV‐16 RNA was analyzed to confirm E6 and/or E7 expression. Incidence data were obtained from the Swedish Cancer Registry. An overall increase in the incidence of base of tongue cancer from 0.15/100,000 person‐years during 1970–1974 to 0.47/100,000 person‐years during 2005–2007 was found in Sweden. The prevalence of HPV in base of tongue cancer in Stockholm county increased from 58% during 1998–2001 to 84% during 2004–2007 (p < 0.05). In the HPV‐positive tumors, HPV‐16 dominated (86%) but interestingly, HPV33 was detected in as many as 10%. E6 and/or E7 RNA were found in 85% of the samples tested. The incidence of base of tongue cancer, as well as the proportion of HPV‐positive tumors, has increased in Sweden during the study period, suggesting that HPV may contribute to this increase.

Background Persistent infection with high-risk human papillomavirus can lead to cervical dysplasia and cancer. Recent studies have suggested associations between the composition of the vaginal microbiota, infection with human papillomavirus (HPV) and progression to cervical dysplasia and cancer.Objective To assess how specific cervico-vaginal microbiota compositions are associated with HPV infection, cervical dysplasia and cancer, we conducted a systematic review and network metaanalysis (registered in PROSPERO: CRD42018112862).Search strategy PubMed, Web of science, Embase and Cochrane database.Selection criteria All original studies describing at least two community state types of bacteria (CST), based on molecular techniques enabling identification of bacteria, and reporting the association with HPV infection, cervical dysplasia and/or cervical cancer.Data collection and analysis For the meta-analysis, a network map was constructed to provide an overview of the network relationships and to assess how many studies provided direct evidence for the different vaginal microbiota compositions and HPV, cervical dysplasia or cancer. Thereafter, the consistency of the model was assessed, and forest plots were constructed to pool and summarise the available evidence, presenting odds ratios and 95% confidence intervals.Main results Vaginal microbiota dominated by non-Lactobacilli species or Lactobacillus iners were associated with three to five times higher odds of any prevalent HPV and two to three times higher for high-risk HPV and dysplasia/cervical cancer compared with Lactobacillus crispatus.Conclusions These findings suggest an association between certain bacterial community types of the vaginal microbiota and HPV infection and HPV-related disease. This may be useful for guiding treatment options or serve as biomarkers for HPV-related disease.Tweetable abstract This network meta-analysis suggests an association between different vaginal bacterial community types and the risk of HPV.

The generation of induced pluripotent stem cells (iPSCs) from differentiated somatic cells by over-expression of several transcription factors has the potential to cure many genetic and degenerative diseases currently recalcitrant to traditional clinical approaches. One such genetic disease is β-thalassemia major (Cooley's anemia). This disease is caused by either a point mutation or the deletion of several nucleotides in the β-globin gene, and it threatens the lives of millions of people in China. In the present study, we successfully generated iPSCs from fibroblasts collected from a 2-year-old patient who was diagnosed with a homozygous 41/42 deletion in his β-globin gene. More importantly, we successfully corrected this genetic mutation in the β-thalassemia iPSCs by homologous recombination. Furthermore, transplantation of the genetically corrected iPSCs-derived hematopoietic progenitors into sub-lethally irradiated immune deficient SCID mice showed improved hemoglobin production compared with the uncorrected iPSCs. Moreover, the generation of human β-globin could be detected in the mice transplanted with corrected iPSCs-derived hematopietic progenitors. Our study provides strong evidence that iPSCs generated from a patient with a genetic disease can be corrected by homologous recombination and that the corrected iPSCs have potential clinical uses.

Upon entry into host cells, intracellular bacterial pathogens establish a variety of replicative niches. Although some remodel phagosomes, others rapidly escape into the cytosol of infected cells. Little is currently known regarding how professional intracytoplasmic pathogens, including Shigella, mediate phagosomal escape. Shigella, like many other Gram-negative bacterial pathogens, uses a type III secretion system to deliver multiple proteins, referred to as effectors, into host cells. Here, using an innovative reductionist-based approach, we demonstrate that the introduction of a functional Shigella type III secretion system, but none of its effectors, into a laboratory strain of Escherichia coli is sufficient to promote the efficient vacuole lysis and escape of the modified bacteria into the cytosol of epithelial cells. This establishes for the first time, to our knowledge, a direct physiologic role for the Shigella type III secretion apparatus (T3SA) in mediating phagosomal escape. Furthermore, although protein components of the T3SA share a moderate degree of structural and functional conservation across bacterial species, we show that vacuole lysis is not a common feature of T3SA, as an effectorless strain of Yersinia remains confined to phagosomes. Additionally, by exploiting the functional interchangeability of the translocator components of the T3SA of Shigella, Salmonella, and Chromobacterium, we demonstrate that a single protein component of the T3SA translocon—Shigella IpaC, Salmonella SipC, or Chromobacterium CipC—determines the fate of intracellular pathogens within both epithelial cells and macrophages. Thus, these findings have identified a likely paradigm by which the replicative niche of many intracellular bacterial pathogens is established.

Human papillomavirus (HPV) vaccines, which were introduced in many countries in the past decade, have shown promising results in decreasing HPV infection and related diseases, such as warts and precancerous lesions. In this review, we present the updated information about current HPV vaccines, focusing on vaccine coverage and efficacy. In addition, pan-gender vaccination and current clinical trials are also discussed. Currently, more efforts should be put into increasing the vaccine’s coverage, especially in low- and middle-income countries. Provision of education on HPV and vaccination is one of the most important methods to achieve this. Vaccines that target HPV types not included in current vaccines are the next stage in vaccine development. In the future, all HPV-related cancers, such as head and neck cancer, and anal cancer, should be tracked and evaluated, especially in countries that have introduced pan-gender vaccination programs. Therapeutic vaccines, in combination with other cancer treatments, should continue to be investigated.

Human papillomavirus (HPV) causes cervical, head, and neck cancers. We studied 483 patients at a youth clinic in Stockholm, Sweden, and found oral HPV prevalence was 9.3% and significantly higher for female youth with than without cervical HPV infection (p = 0.043). Most oral HPV types matched the co-occurring cervical types.