OBJECTIVES: This review assessed the rate of high-risk human papillomavirus (HPV) infection among women living in sub-Saharan Africa. It also determined the prevalence of high-risk HPV (hrHPV) among human immunodeficiency virus (HIV) seropositive (HIV+) and seronegative (HIV-) women in sub-Saharan Africa, pre-2010 and post-2010.METHODS: In this systematic review, Google Scholar, PubMed Central, and Embase were searched to identify cohort and case-control studies that investigated the relationship between HIV and HPV infection. The database searches yielded 17 studies published between 1999 and 2018.RESULTS: In the general population, the prevalence of any HPV/multiple HPV infections was higher among HIV+ (53.6/22.6%) than among HIV- women (26.5/7.3%) with odds ratios of 3.22 and 3.71, respectively (95% confidence interval, 3.00 to 3.42 and 2.39 to 5.75, p< 0.001). The prevalent HPV genotypes among HIV+ and HIV- women diagnosed with invasive cervical cancer (ICC) were HPV-16/18 and HPV-45. The prevalence of HPV-16, HPV-18, and HPV-45 was lower in 1999-2010 (3.8, 1.7, and 0.8%, respectively) than in 2011-2018 (19.1, 6.0, and 3.6%, respectively). Among women diagnosed with ICC, HIV+ women had a higher prevalence of HPV-56, HPV-31, and HPV-51 (7.3, 5.3, and 3.3%, respectively) than HIV- women (1.3, 2.2, and 0.4%, p< 0.001, p= 0.050, and p= 0.013, respectively).CONCLUSIONS: The prevalence of HPV infection, multiple HPV infections, and non-vaccine HPV types were higher among HIV+ women than among HIV- women in sub-Saharan Africa. Although HIV infection influences the distribution of HPV types, this study suggests that cervical cancer incidence in sub-Saharan Africa is primarily driven by the prevalence of vaccine hrHPVs, especially HPV-16 and HPV-18.

Background/Objective: Cervical Cancer is the 6th most common and 3rd most deadly cancer among women. Despite the fact that the majority of the countries in Asia and Africa have a similar economy and low life expectancy, the mean age-standardized incidence rate (ASIR) of cervical cancer is substantially higher in Africa than in Asia. This study identified the correlates of the higher ASIR rates in Africa relative to Asia against two timelines; 2004-2009 and 2010-2017. Methods: Peer-reviewed articles published between 2004 and 2017 were selected using the PRISMA standard. Sources of articles included Google Scholar, Scopus, PubMed Central, and EMBASE. Search keywords included: HPV genotypes, cervical cancer, HPV vaccine, and multiple infections in Africa and Asia. Result: Twenty-nine and seventeen full-length articles were selected from Africa and Asia, respectively. The pooled prevalence of HPV infection up to 2017 was higher in Africa (41.8%; 95% CI: 35.9, 47.7) than in Asia (24.2%; 95% CI: 16.22, 32.2) at p< 0.001. Between 2004-2009 and 2010-2017 timelines, the pooled prevalence of HPV infection decreased from 49.1% to 36.7% (OR’: 1.66, 95% CI: 1.51-1.80) in Africa and increased from 16.9% to 20.5% (OR’: 0.79, 95% CI: 0.71-0.86) in Asia. However, the pooled prevalence of multiple HPV infections and non-vaccine high-risk HPV infections were higher among African women diagnosed with cancer (30.9% and 5.2%) than their Asian counterparts (21.0% and 2.0%, respectively) at p< 0.001. Additionally, the pooled prevalence of the five most prevalent high-risk HPV types in Africa were HPV16 (35.3%), HPV52 (14.2%), HPV35 (12.4%), HPV18 (10.4%), and HPV58 (10.0%), while that of Asia were HPV16 (37.3%), HPV52 (16.2%), HPV58 (14.7%), HPV33 (7.4%) and HPV18 (7.2%). Conclusion: This study suggests that the higher prevalence of HPV, multiple HPV and non-vaccine HPV infections could be responsible for the higher ASIR in Africa than in Asia.

Purpose: Intraductal papillary mucinous neoplasms (IPMN) occur in 5% to 10% of the population, but only a small minority progress to pancreatic ductal adenocarcinoma (PDAC). The lack of accurate predictors of high-risk disease leads to both unnecessary operations for indolent neoplasms and missed diagnoses of PDAC. Digital spatial RNA profiling (DSP-RNA) provides an opportunity to define and associate transcriptomic states with cancer risk. Experimental Design: We performed whole-transcriptome DSP-RNA profiling on 10 IPMN specimens encompassing the spectrum of dysplastic changes from normal duct to cancer. Epithelial regions within each tissue were annotated as normal duct, low-grade dysplasia, high-grade dysplasia, or invasive carcinoma. The resulting digital gene expression data were analyzed with R/Bioconductor. Results: Our analysis uncovered three distinct epithelial transcriptomic states—“normal-like” (cNL), “low risk” (cLR), and “high risk” (cHR)—which were significantly associated with pathologic grade. Furthermore, the three states were significantly correlated with the exocrine, classical, and basal-like molecular subtypes described in PDAC. Specifically, exocrine function diminished in cHR, classical activation distinguished neoplasia (cLR and cHR) from cNL, and basal-like genes were specifically upregulated in cHR. Intriguingly, markers of cHR were detected in normal duct and low-grade dysplasia regions from specimens with PDAC but not from specimens containing only low-grade IPMN. Conclusions: DSP-RNA of IPMN revealed low-risk (indolent) and high-risk (malignant) expression programs that correlated with the activity of exocrine and basal-like PDAC signatures, respectively, and distinguished pathologically low-grade specimens from malignant specimens. These findings contextualize IPMN pathogenesis and have the potential to improve risk stratification.

This cross-sectional study evaluated the expression of miR-let-7b, miR-21, miR-125b, miR-143, miR-145, miR-155, miR-182, miR-200c, p53 gene, Ki67, SCCA1 and CD4+ T-cell counts among 319 women, to Epstein-Barr virus, human papillomavirus and herpes simplex virus 2 mono-infections and co-infections, using enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction methods. This study suggests that malignancies associated with viral co-infection could be diagnosed early by monitoring cluster of differentiation 4+ T-cell counts and serum expression of miR-145 and miR-182.

Objective: The high mortality associated with cervical cancer is due to low uptake of Pap smear test, lack of early diagnostic biomarkers and less-invasive approach, and late presentation of the disease. This study evaluated the expression of hsa-miR-let-7b, hsa-miR-2 1. hsa-miR-125b, hsa-miR-143, hsa-miR-145, hsa-miR-146a, hsa-miR-155, hsa-miR-182, hsa-miR-200c, and p53 in serum and cervix in relation to classes of Pap smear, in a bid to identify a serum panel for early diagnosis of cervical lesions. Methodology: This study included 329 women; 159 healthy women (HW), 46 cervicitis, 46 atypical squamous cells of undetermined significance (ASCUS), 40 low-grade squamous cell intraepithelial lesion (LSIL), 28 high-grade squamous cell intraepithelial lesion (HSIL), and 10 squamous cell carcinoma (SCC). Expression of microRNAs (miRNAs) and p53 was assessed using reverse transcriptase polymerase chain reaction. Results: Except for miR-143 and miR-146a, significant correlations were observed between serum and cervix expression of miRNAs and p53 in relation to levels and classes of Pap smear (P < 0.05). Relatively, higher expression of miR-21, miR-146a, miR-155, miR-182, and miR-200c and lower expression of let-7b and miR-145 were observed in sera associated with cervical abnormalities than in sera associated with normal cervix (P < 0.0001, P = 0.001. P < 0.0001, P = 0.003. P = 0.007, P= 0.036. and P = 0.046, respectively). Higher and lower expression of p53 was observed in women diagnosed of LSIL and SCC. respectively, than in HW (P < 0.0001). Conclusion: This study suggests that serum expression of miR-21, miR-182, let-7b. miR-145, and p53 is comparable to cervical cell expression and could be useful in differentiating abnormal cervix from the healthy cervix.

Pancreatic cancer is associated with a high rate of metastasis and poor prognosis. The formation of a premetastatic niche (PMN) facilitates cancer cell spread and contributes to cancer mortality. Using murine pancreatic cancer models based on expression of oncogenic KRAS in the pancreas epithelium, we discovered that remodeling of the lung microenvironment occurred in mice bearing pancreatic precursor lesions prior to cancer formation. This early-lesion PMN resembled the PMN in cancer-bearing mice, and both feature characteristics of overt metastasis, such as transcriptional reprogramming, activation of fibroblast STAT3 signaling, and infiltration of immunosuppressive arginase 1–positive macrophages. Both patients with pancreatic cancer and mouse models demonstrated elevated serum IL6. Inactivating oncogenic KRAS reduced serum IL6 and reverted fibroblast STAT3 phosphorylation in mouse lungs; loss of lung fibroblast STAT3 phosphorylation was similarly observed when mice were treated with the pan-RAS inhibitor RMC-7977. Whereas arginase 1–positive macrophage infiltration was dispensable for fibroblast STAT3 activation, IL6 blockade inhibited lung fibroblast STAT3 activation. Functionally, fibroblast STAT3 activation was necessary for lung metastasis establishment and growth. Interestingly, activation of STAT3 in the PMN was present in the lungs but not in the liver, in which fibroblast reprogramming occurred only in overt metastasis, pointing to organ-specific PMN formation. In human metastasis samples, phosphorylated STAT3 in fibroblasts was similarly more abundant in the lungs than liver. Together, these data point to organ-specific mechanisms driving formation of the PMN and indicate that reprogramming of the microenvironment prior to metastasis might support early dissemination of pancreatic cancer. Significance: Pancreatic oncogenic KRAS drives premetastatic niche formation in the lungs, but not liver, through fibroblast STAT3 activation to promote metastasis, indicating a lung-specific vulnerability for treating pancreatic cancer metastasis. See related commentary by Mucciolo and Biffi, p. 7