Saving the World's Women from Cervical Cancer Tsu, Vivien; Jerónimo, José
New England journal of medicine/The New England journal of medicine,
2016-Jun-30, Letnik:
374, Številka:
26
Journal Article
Human papillomavirus and cervical cancer Schiffman, Mark, Prof; Castle, Philip E, PhD; Jeronimo, Jose, MD ...
The Lancet (British edition),
09/2007, Letnik:
370, Številka:
9590
Journal Article
Recenzirano
Summary Cervical cancer is the second most common cancer in women worldwide, and knowledge regarding its cause and pathogenesis is expanding rapidly. Persistent infection with one of about 15 ...genotypes of carcinogenic human papillomavirus (HPV) causes almost all cases. There are four major steps in cervical cancer development: infection of metaplastic epithelium at the cervical transformation zone, viral persistence, progression of persistently infected epithelium to cervical precancer, and invasion through the basement membrane of the epithelium. Infection is extremely common in young women in their first decade of sexual activity. Persistent infections and precancer are established, typically within 5–10 years, from less than 10% of new infections. Invasive cancer arises over many years, even decades, in a minority of women with precancer, with a peak or plateau in risk at about 35–55 years of age. Each genotype of HPV acts as an independent infection, with differing carcinogenic risks linked to evolutionary species. Our understanding has led to improved prevention and clinical management strategies, including improved screening tests and vaccines. The new HPV-oriented model of cervical carcinogenesis should gradually replace older morphological models based only on cytology and histology. If applied wisely, HPV-related technology can minimise the incidence of cervical cancer, and the morbidity and mortality it causes, even in low-resource settings.
Summary Breast and cervical cancers are the commonest cancers diagnosed in women living in low-income and middle-income countries (LMICs), where opportunities for prevention, early detection, or ...both, are few. Yet several cost-effective interventions could be used to reduce the burden of these two cancers in resource-limited environments. Population- wide vaccination against human papillomavirus (HPV) linked to cervical screening, at least once, for adult women has the potential to reduce the incidence of cervical cancer substantially. Strategies such as visual inspection with acetic acid and testing for oncogenic HPV types could make prevention of cervical cancer programmatically feasible. These two cancers need not be viewed as inevitably fatal, and can be cured, particularly if detected and treated at an early stage. Investing in the health of girls and women is an investment in the development of nations and their futures. Here we explore ways to lessen the divide between LMICs and high-income countries for breast and cervical cancers.
Developing efficient wide‐bandgap perovskites is critical to exploit the benefits of a multi‐absorber solar cell and engineering commercially attractive tandem solar cells. Here, a robust, ...additive‐free, methylammonium‐free triple halide composition for the fabrication of close‐to‐ideal wide‐bandgap perovskites (1.64 eV) is reported. The introduction of low percentages of chloride into the perovskite layer avoided photoinduced halide segregation and lead to an evident improvement in the crystallization process, reaching enhanced open‐circuit voltages as high as 1.23 V. A perovskite of these characteristics is introduced for the first time in a p‐i‐n single‐junction configuration using a self‐assembled monolayer, with devices achieving photoconversion efficiencies of up to 22.6% with ultra‐high stability, retaining ≈80% of their initial efficiency after >1000 h of continuous operation unencapsulated in a nitrogen atmosphere at 85 °C. This result paves the way toward highly efficient multi‐junction tandem solar cells, bringing perovskite technology closer to commercialization.
A triple halide composition, additive‐ and methylammonium‐free, fabricates wide‐bandgap perovskites (1.64 eV). Small amounts of chloride prevent photoinduced halide segregation and improve the crystallization process significantly, enhancing open‐circuit voltages (1.23 V). These characteristics are introduced for the first time in a p‐i‐n single‐junction configuration employing a self‐assembled monolayer. Devices achieve up to 22.6% photoconversion efficiencies with exceptional stability at 85 °C.
Metal halide perovskite solar cells may work for application in extreme temperatures, such as those experienced under extraterrestrial conditions. However, device performances in extreme temperatures ...are poorly investigated. This work systematically explores the performance of perovskite solar cells between −160 and 150 °C. In situ grazing‐incidence wide‐angle X‐ray scattering discloses perovskite phase transition and crystal disordering as dominant factors for the temperature‐dependent device efficiency deterioration. It is shown that perovskite lattice strain and relaxation originating from extreme temperature variations are recoverable, and so are the perovskite structure and photovoltaic performances. This work provides insights into the functioning under extreme temperatures, clarifying bottlenecks to overcome and the potential for extraterrestrial applications.
During temperature variation, perovskite experiences the phase transition and crystal disorder, functioning as the dominant factor causing device efficiency deterioration. Such structural evolution is found to be related to temperature‐induced lattice strain. By relieving the lattice strain, the device possesses the recoverable photovoltaic performance, highlighting the challenges and the potentials of perovskite‐based optoelectronics operating at extreme temperature environments.
Incorporation of a third monovalent cation has been shown to improve the perovskite solar cell performance and stability. In this work, an in-depth study has been carried out to understand the effect ...of Cs+ and K+ cations on charge carrier dynamics in methylammonium-Formamidinium based solar cell. Different spectroscopic techniques together with electrical studies have been employed to determine the role of these cations on the charge carrier traps, charge transport, charge carrier extraction, recombination, etc. Incorporation of Cs+ leads to superior crystallinity and larger grains resulting in improved passivation, reduction of non-radiative losses and improved charge transport within the perovskite layer which resulted in improved cell performance than that with K+ incorporated device. The PL quenching at short-circuit, high recombination resistance deduced from the impedance spectra, lowest Urbach energy, and high electroluminescence of the Cs+ incorporated perovskite concur with the large and colunmnar grain growth with Cs+ incorporation. With Cs+, the device efficiency reach 19.8% with high fill factor of 80.28%, whereas K+ incorporated devices demonstrate only 16.16% efficiency with a fill factor of 71.76%. Although K+ substitution leads to better stability, MAFA:Cs+ devices are superior in terms of cell performance.
•Triple cation perovskite devices are studied to compare the performance with Cs+ and K+.•Cs + incorporated perovskite shows large columnar grain growth.•Suppression of non-radiative recombination and charge collection are studied by different spectroscopic techniques.•Cs + incorporated devices show better performance while the stability is better with K+.
Abstract The World Health Organization recommends human papillomavirus (HPV) testing for cervical screening. Extended genotyping can identify the highest‐risk HPV‐positive women. An inexpensive, ...rapid, mobile isothermal amplification assay (ScreenFire HPV RS test) was recently redesigned to yield four channels ordered by cancer risk (ie, hierarchical approach): HPV16, HPV18/45, HPV31/33/35/52/58 and HPV39/51/56/59/68. Stored specimens from 2076 women (mean age 30.9) enrolled in a colposcopy clinic, with high HPV prevalence, were tested with ScreenFire. We calculated hierarchical channel positivity and non‐hierarchical channel and type positivity, according to histologic diagnosis (256 cancer, 350 cervical intraepithelial neoplasia CIN3, 409 CIN2, 1020 < CIN2) and known virologic reference results (Linear Array and TypeSeq). Additionally, we analyzed ScreenFire time‐to‐positive up to 60 min by channel and histology. Overall clinical sensitivity for CIN3+ was 94.7% (95% confidence interval 92.6‐96.4), similar to Linear Array (92.3, 89.7‐94.3) and TypeSeq (96.0, 93.9‐97.6). Sensitivity was high for all types and channels. The hierarchical approach was well in line with HPV typing and histologic diagnosis, prioritizing higher risk women having HPV16 and precancer. For HPV16, time‐to‐positive was shorter in women with precancer. ScreenFire showed excellent agreement with research reference typing tests and detection of CIN2+. Risk‐based type results could help guide clinical management of HPV‐positive women. Time‐to‐positive combined with genotyping might be useful. ScreenFire is rapid, mobile, relatively inexpensive and designed for implementation of HPV‐based screening and management, including in lower‐resource settings. Further validation in screening by self‐sampling and practical effectiveness merit evaluation.
Loop electrosurgical excision procedure (LEEP) is the predominant treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN2+) in the United States, yet following treatment approximately 10% ...of women are diagnosed again with CIN2+, necessitating close follow-up of such patients.
Surveillance strategies using cytology and/or human papillomavirus (HPV) testing were compared among women who underwent LEEP (n = 610) in the Atypical Squamous Cells of Undetermined Significance (ASCUS) Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. Cervical specimens, collected at 6-month visits for 2 years, were used for cytology, Hybrid Capture 2 (HC2) detection of carcinogenic HPVs, and PCR for genotyping of carcinogenic and noncarcinogenic HPV types. At exit, women had colposcopy for safety and disease ascertainment.
At the visit post-LEEP (median time: 4.5 months after LEEP), 36.9% 95% confidence interval (95% CI), 32.7-41.1% of women were positive for carcinogenic HPV by PCR and 33.7% (95% CI, 29.7-37.9) had ASCUS or more severe (ASCUS+) cytology. The overall 2-year cumulative incidence of histologically confirmed posttreatment CIN2+ was 7.0%; this could be further stratified by the HPV risk category detected at the 6-month visit after LEEP. The 2-year risk associated with HPV16 positivity was 37.0%, significantly higher than for other carcinogenic HPV types (10.8%, P < 0.001), noncarcinogenic types (1.5%, P < 0.001), or testing HPV negative (0%). Post-LEEP cytology (using a positive threshold of ASCUS+) was 78.1% (95% CI, 60.0-90.7%) sensitive for detection of posttreatment CIN2+. By comparison, PCR for carcinogenic HPV and combination testing (using a positive result from carcinogenic HPV testing or cytology as the test threshold with HPV-negative ASCUS not referred) were significantly more sensitive (96.9% for each, P = 0.03); HC2 alone was nonsignificantly more sensitive (90.6%, P = 0.3). Specificity was similar for ASCUS+ cytology (69.1%, 95% CI, 64.6-73.3%) and PCR for carcinogenic HPV (67.1%, P = 0.5), yet was lower for HC2 (63.8%, P = 0.048) and combination testing (62.9%, P = 0.02).
Women who tested positive after LEEP for carcinogenic HPV types, especially HPV16, had high risk of subsequent CIN2+. HPV-based detection methods, alone or in combination with cytology, may be useful to incorporate in post-LEEP management strategies.
The health concerns of women in their mid-adult years - when the prime age of reproduction has passed - have been traditionally given little or no attention by health systems and donors, despite the ...heavy burden that diseases such as breast and cervical cancer impose on women and their families. The risk of sexually transmitted infections that accompanies sexual relations and the risk of death and morbidity associated with pregnancy have long been recognized and have stimulated major control efforts that are finally yielding positive results. Much less attention has been focused, however, on how experiences in early life can affect women's health in adulthood. Breast and cervical cancers kill more women than any other types of cancer in all parts of the developing world. In most of Asia and Latin America and some African countries, deaths from these two forms of cancer now outnumber pregnancy-related deaths. There are five compelling reasons for focusing on these cancers now to try to reverse these epidemiologic trends: (i) the burden of breast and cervical cancer is large and is growing; (ii) effective screening and treatment are available; (iii) research is generating new knowledge; (iv) there are opportunities for synergy with other health programmes; and (v) noncommunicable diseases are the focus of much current interest.
Where resources are available, the World Health Organization recommends cervical cancer screening with human papillomavirus (HPV) DNA testing and subsequent treatment of HPV-positive women with ...timely cryotherapy. Newer technologies may facilitate a same-day screen-and-treat approach, but these testing systems are generally too expensive for widespread use in low-resource settings.
To assess the value of a hypothetical point-of-care HPV test, we used a mathematical simulation model of the natural history of HPV and data from the START-UP multi-site demonstration project to estimate the health benefits and costs associated with a shift from a 2-visit approach (requiring a return visit for treatment) to 1-visit HPV testing (i.e., screen-and-treat). We estimated the incremental net monetary benefit (INMB), which represents the maximum additional lifetime cost per woman that could be incurred for a new point-of-care HPV test to be cost-effective, depending on expected loss to follow-up between visits (LTFU) in a given setting.
For screening three times in a lifetime at 100% coverage of the target population, when LTFU was 10%, the INMB of the 1-visit relative to the 2-visit approach was I$13 in India, I$36 in Nicaragua, and I$17 in Uganda. If LTFU was 30% or greater, the INMB values for the 1-visit approach in all countries was equivalent to or exceeded total lifetime costs associated with screening three times in a lifetime. At a LTFU level of 70%, the INMB of the 1-visit approach was I$127 in India, I$399 in Nicaragua, and I$121 in Uganda.
These findings indicate that point-of-care technology for cervical cancer screening may be worthy of high investment if linkage to treatment can be assured, particularly in settings where LTFU is high.
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