Current and Emerging Molecular Tests for Human Papillomavirus–Related Neoplasia in the Genomic Era

Laboratory tests have a key role in preventing human papillomavirus (HPV)-driven carcinomas and in guiding therapeutic interventions. An understanding of the virology, immunology, and carcinogenesis of HPV is essential for choosing appropriate diagnostic test modalities and developing new and even more effective cancer prevention strategies. HPV infects basal epithelial cells on multiple surfaces and induces carcinoma primarily in the cervix and the oropharynx. HPV types are stratified as high risk or low risk based on their carcinogenic potential. During oncogenesis, HPV interferes with cell cycle regulation and incites DNA damage responses that thwart apoptosis and enable mutations to accumulate. Such mutations are an adverse effect of innate and adaptive antiviral immune responses that up-regulate DNA-editing enzymes, with natural selection of cells having a chromosomally integrated viral genome lacking expression of viral proteins targeted by the immune system. Infected cancers share a similar mutation signature, reflecting the effect of apolipoprotein B mRNA-editing catalytic polypeptide enzyme DNA-editing enzymes. It is feasible that genomic tests for characteristic mutations or methylation signatures, along with tests for dysregulated HPV gene expression, add value in predicting behavior of premalignant lesions. Furthermore, these tumor markers in cell-free DNA of plasma or body fluids may one day assist in early detection or monitoring cancer burden during treatment

Cholera and Climate Change: Pursuing Public Health Adaptation Strategies in the Face of Scientific Debate

Climate change will affect the prevalence, distribution, and lethality of many diseases, from mosquito-borne diseases like malaria and dengue fever to directly infectious diseases like influenza to water-borne diseases like cholera and cryptosporidia. This Article focuses on one of the current scientific debates surrounding cholera and the implications of that debate for public health-related climate change adaptation strategies. Since the 1970s, Rita Colwell and her co-researchers have been arguing a local reservoir hypothesis for cholera, emphasizing that river, estuarine, and coastal waters often contain more dormant forms of cholera attached to copepods, a form of zooplankton. Under this hypothesis, climatically driven increases in sea surface temperatures, sea surface levels, and phytoplankton production—such as during El Niño years or because of climate change—can then spur cholera outbreaks in vulnerable coastal communities. As such, the local reservoir hypothesis has immediate implications for climate change public health adaptation strategies. In November 2017, however, two teams of scientists published genomic research in Science concluding that epidemic and pandemic cholera outbreaks in the Americas and Africa originate from Asia, suggesting that the local reservoir hypothesis needs modification. The two research articles also suggested a very different strategy for dealing with cholera in the Anthropocene—namely, genetic detection and intensely focused control efforts in Asia. This Article examines in more detail this emerging scientific debate about cholera reservoirs and the ultimate source(s) of cholera outbreaks and epidemics. It then explores the implications of that debate for climate change public health adaptation strategies, suggesting simultaneously that the cholera debate is one concrete example of how identifying the stakes at issue in different climate change adaptation strategies can help communities and nations to choose appropriate adaptation strategies despite scientific uncertainty