Continuing benefits of the Montreal Protocol and protection of the stratospheric ozone layer for human health and the environment.

The protection of Earth's stratospheric ozone (O3) is an ongoing process under the auspices of the universally ratified Montreal Protocol and its Amendments and adjustments. A critical part of this process is the assessment of the environmental issues related to changes in O3. The United Nations Environment Programme's Environmental Effects Assessment Panel provides annual scientific evaluations of some of the key issues arising in the recent collective knowledge base. This current update includes a comprehensive assessment of the incidence rates of skin cancer, cataract and other skin and eye diseases observed worldwide; the effects of UV radiation on tropospheric oxidants, and air and water quality; trends in breakdown products of fluorinated chemicals and recent information of their toxicity; and recent technological innovations of building materials for greater resistance to UV radiation. These issues span a wide range of topics, including both harmful and beneficial effects of exposure to UV radiation, and complex interactions with climate change. While the Montreal Protocol has succeeded in preventing large reductions in stratospheric O3, future changes may occur due to a number of natural and anthropogenic factors. Thus, frequent assessments of potential environmental impacts are essential to ensure that policies remain based on the best available scientific knowledge.

Stratospheric ozone, UV radiation, and climate interactions.

This assessment provides a comprehensive update of the effects of changes in stratospheric ozone and other factors (aerosols, surface reflectivity, solar activity, and climate) on the intensity of ultraviolet (UV) radiation at the Earth's surface. The assessment is performed in the context of the Montreal Protocol on Substances that Deplete the Ozone Layer and its Amendments and Adjustments. Changes in UV radiation at low- and mid-latitudes (0-60°) during the last 25 years have generally been small (e.g., typically less than 4% per decade, increasing at some sites and decreasing at others) and were mostly driven by changes in cloud cover and atmospheric aerosol content, caused partly by climate change and partly by measures to control tropospheric pollution. Without the Montreal Protocol, erythemal (sunburning) UV irradiance at northern and southern latitudes of less than 50° would have increased by 10-20% between 1996 and 2020. For southern latitudes exceeding 50°, the UV Index (UVI) would have surged by between 25% (year-round at the southern tip of South America) and more than 100% (South Pole in spring). Variability of erythemal irradiance in Antarctica was very large during the last four years. In spring 2019, erythemal UV radiation was at the minimum of the historical (1991-2018) range at the South Pole, while near record-high values were observed in spring 2020, which were up to 80% above the historical mean. In the Arctic, some of the highest erythemal irradiances on record were measured in March and April 2020. For example in March 2020, the monthly average UVI over a site in the Canadian Arctic was up to 70% higher than the historical (2005-2019) average, often exceeding this mean by three standard deviations. Under the presumption that all countries will adhere to the Montreal Protocol in the future and that atmospheric aerosol concentrations remain constant, erythemal irradiance at mid-latitudes (30-60°) is projected to decrease between 2015 and 2090 by 2-5% in the north and by 4-6% in the south due to recovering ozone. Changes projected for the tropics are ≤ 3%. However, in industrial regions that are currently affected by air pollution, UV radiation will increase as measures to reduce air pollutants will gradually restore UV radiation intensities to those of a cleaner atmosphere. Since most substances controlled by the Montreal Protocol are also greenhouse gases, the phase-out of these substances may have avoided warming by 0.5-1.0 °C over mid-latitude regions of the continents, and by more than 1.0 °C in the Arctic; however, the uncertainty of these calculations is large. We also assess the effects of changes in stratospheric ozone on climate, focusing on the poleward shift of climate zones, and discuss the role of the small Antarctic ozone hole in 2019 on the devastating "Black Summer" fires in Australia. Additional topics include the assessment of advances in measuring and modeling of UV radiation; methods for determining personal UV exposure; the effect of solar radiation management (stratospheric aerosol injections) on UV radiation relevant for plants; and possible revisions to the vitamin D action spectrum, which describes the wavelength dependence of the synthesis of previtamin D3 in human skin upon exposure to UV radiation.

Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2021.

The Environmental Effects Assessment Panel of the Montreal Protocol under the United Nations Environment Programme evaluates effects on the environment and human health that arise from changes in the stratospheric ozone layer and concomitant variations in ultraviolet (UV) radiation at the Earth's surface. The current update is based on scientific advances that have accumulated since our last assessment (Photochem and Photobiol Sci 20(1):1-67, 2021). We also discuss how climate change affects stratospheric ozone depletion and ultraviolet radiation, and how stratospheric ozone depletion affects climate change. The resulting interlinking effects of stratospheric ozone depletion, UV radiation, and climate change are assessed in terms of air quality, carbon sinks, ecosystems, human health, and natural and synthetic materials. We further highlight potential impacts on the biosphere from extreme climate events that are occurring with increasing frequency as a consequence of climate change. These and other interactive effects are examined with respect to the benefits that the Montreal Protocol and its Amendments are providing to life on Earth by controlling the production of various substances that contribute to both stratospheric ozone depletion and climate change.

Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2020.

This assessment by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) provides the latest scientific update since our most recent comprehensive assessment (Photochemical and Photobiological Sciences, 2019, 18, 595-828). The interactive effects between the stratospheric ozone layer, solar ultraviolet (UV) radiation, and climate change are presented within the framework of the Montreal Protocol and the United Nations Sustainable Development Goals. We address how these global environmental changes affect the atmosphere and air quality; human health; terrestrial and aquatic ecosystems; biogeochemical cycles; and materials used in outdoor construction, solar energy technologies, and fabrics. In many cases, there is a growing influence from changes in seasonality and extreme events due to climate change. Additionally, we assess the transmission and environmental effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for the COVID-19 pandemic, in the context of linkages with solar UV radiation and the Montreal Protocol.

Environmental effects of stratospheric ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, update 2019.

This assessment, by the United Nations Environment Programme (UNEP) Environmental Effects Assessment Panel (EEAP), one of three Panels informing the Parties to the Montreal Protocol, provides an update, since our previous extensive assessment (Photochem. Photobiol. Sci., 2019, 18, 595-828), of recent findings of current and projected interactive environmental effects of ultraviolet (UV) radiation, stratospheric ozone, and climate change. These effects include those on human health, air quality, terrestrial and aquatic ecosystems, biogeochemical cycles, and materials used in construction and other services. The present update evaluates further evidence of the consequences of human activity on climate change that are altering the exposure of organisms and ecosystems to UV radiation. This in turn reveals the interactive effects of many climate change factors with UV radiation that have implications for the atmosphere, feedbacks, contaminant fate and transport, organismal responses, and many outdoor materials including plastics, wood, and fabrics. The universal ratification of the Montreal Protocol, signed by 197 countries, has led to the regulation and phase-out of chemicals that deplete the stratospheric ozone layer. Although this treaty has had unprecedented success in protecting the ozone layer, and hence all life on Earth from damaging UV radiation, it is also making a substantial contribution to reducing climate warming because many of the chemicals under this treaty are greenhouse gases.

Ozone-climate interactions and effects on solar ultraviolet radiation.

This report assesses the effects of stratospheric ozone depletion and anticipated ozone recovery on the intensity of ultraviolet (UV) radiation at the Earth's surface. Interactions between changes in ozone and changes in climate, as well as their effects on UV radiation, are also considered. These evaluations focus mainly on new knowledge gained from research conducted during the last four years. Furthermore, drivers of changes in UV radiation other than ozone are discussed and their relative importance is assessed. The most important of these factors, namely clouds, aerosols and surface reflectivity, are related to changes in climate, and some of their effects on short- and long-term variations of UV radiation have already been identified from measurements. Finally, projected future developments in stratospheric ozone, climate, and other factors affecting UV radiation have been used to estimate changes in solar UV radiation from the present to the end of the 21st century. New instruments and methods have been assessed with respect to their ability to provide useful and accurate information for monitoring solar UV radiation at the Earth's surface and for determining relevant exposures of humans. Evidence since the last assessment reconfirms that systematic and accurate long-term measurements of UV radiation and stratospheric ozone are essential for assessing the effectiveness of the Montreal Protocol and its Amendments and adjustments. Finally, we have assessed aspects of UV radiation related to biological effects and human health, as well as implications for UV radiation from possible solar radiation management (geoengineering) methods to mitigate climate change.

Environmental effects of ozone depletion, UV radiation and interactions with climate change: UNEP Environmental Effects Assessment Panel, update 2017.

The Environmental Effects Assessment Panel (EEAP) is one of three Panels of experts that inform the Parties to the Montreal Protocol. The EEAP focuses on the effects of UV radiation on human health, terrestrial and aquatic ecosystems, air quality, and materials, as well as on the interactive effects of UV radiation and global climate change. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than previously held. Because of the Montreal Protocol, there are now indications of the beginnings of a recovery of stratospheric ozone, although the time required to reach levels like those before the 1960s is still uncertain, particularly as the effects of stratospheric ozone on climate change and vice versa, are not yet fully understood. Some regions will likely receive enhanced levels of UV radiation, while other areas will likely experience a reduction in UV radiation as ozone- and climate-driven changes affect the amounts of UV radiation reaching the Earth's surface. Like the other Panels, the EEAP produces detailed Quadrennial Reports every four years; the most recent was published as a series of seven papers in 2015 (Photochem. Photobiol. Sci., 2015, 14, 1-184). In the years in between, the EEAP produces less detailed and shorter Update Reports of recent and relevant scientific findings. The most recent of these was for 2016 (Photochem. Photobiol. Sci., 2017, 16, 107-145). The present 2017 Update Report assesses some of the highlights and new insights about the interactive nature of the direct and indirect effects of UV radiation, atmospheric processes, and climate change. A full 2018 Quadrennial Assessment, will be made available in 2018/2019.

Ultraviolet radiation and effects on humans: the paradigm of maternal vitamin D production during pregnancy.

Current evidence indicates that neonates born of mothers with vitamin D deficiency during pregnancy have greater risk for developing hypocalcemia, rickets and extra-skeletal disorders. Despite the classic knowledge that ultraviolet-B (UVB) exposure is the most efficient way for a future mother to obtain optimal vitamin D concentrations, no current consensus or clinical recommendations exist regarding the duration and timing of UVB exposure for pregnant women. This article offers a narrative review of available data regarding how UVB exposure affects maternal vitamin D production during pregnancy, along with a discourse on clinical implications of this public health issue. Future studies would benefit from adopting UVB exposure estimates to recommend appropriate UVB exposure to pregnant women. Doing so could provide a more holistic and practical approach in managing maternal hypovitaminosis D during pregnancy.

Projected changes in erythemal and vitamin D effective irradiance over northern-hemisphere high latitudes.

Simulations of the monthly mean noon UV index and the effective dose for the production of vitamin D in the human skin have been performed for local noon for the latitude band 55°N-85°N using a radiative transfer model. The magnitude and spatial distribution of the changes estimated for the two quantities between the past (1955-1965 mean), the present (2010-2020 mean) and the future (2085-2095 mean) are discussed and the main drivers for these changes are identified. The irradiance simulations are based on simulations and projections of total ozone, surface reflectivity and aerosol optical depth derived from models used in the fifth phase of the Coupled Model Intercomparison Project (CMIP-5). The cloud modification factor is also derived from the CMIP-5 models and used to account for the effects of cloudiness. Simulations have been derived for two socioeconomic scenarios: the moderate RCP 4.5 and the extreme RCP 8.5. For the future, the two quantities are projected to be generally lower than in the past and the present, mainly due to the projected super-recovery of stratospheric ozone and reduced surface reflectivity. Although the greatest changes are projected over the Arctic Ocean and do not directly affect humans, the changes over land are also important. Over land, the greatest changes are found in northern Asia, Greenland and the north-east shores of Canada and Alaska. The greatest reductions over land are projected for April under all skies, locally reaching ∼30% for the noon UV index and ∼50% for the noon effective UV dose for the production of vitamin D.

Ozone depletion and climate change: impacts on UV radiation.

We assess the importance of factors that determine the intensity of UV radiation at the Earth's surface. Among these, atmospheric ozone, which absorbs UV radiation, is of considerable importance, but other constituents of the atmosphere, as well as certain consequences of climate change, can also be major influences. Further, we assess the variations of UV radiation observed in the past and present, and provide projections for the future. Of particular interest are methods to measure or estimate UV radiation at the Earth's surface. These are needed for scientific understanding and, when they are sufficiently sensitive, they can serve as monitors of the effectiveness of the Montreal Protocol and its amendments. Also assessed are several aspects of UV radiation related to biological effects and health. The implications for ozone and UV radiation from two types of geoengineering methods that have been proposed to combat climate change are also discussed. In addition to ozone effects, the UV changes in the last two decades, derived from measurements, have been influenced by changes in aerosols, clouds, surface reflectivity, and, possibly, by solar activity. The positive trends of UV radiation observed after the mid-1990s over northern mid-latitudes are mainly due to decreases in clouds and aerosols. Despite some indications from measurements at a few stations, no statistically significant decreases in UV-B radiation attributable to the beginning of the ozone recovery have yet been detected. Projections for erythemal irradiance (UVery) suggest the following changes by the end of the 21(st) century (2090-2100) relative to the present time (2010-2020): (1) Ozone recovery (due to decreasing ozone-depleting substances and increasing greenhouse gases) would cause decreases in UVery, which will be highest (up to 40%) over Antarctica. Decreases would be small (less than 10%) outside the southern Polar Regions. A possible decline of solar activity during the 21(st) century might affect UV-B radiation at the surface indirectly through changes induced in stratospheric ozone. (2) The projected changes in cloud cover would lead to relatively small effects (less than 3%), except at northern high latitudes where increases in cloud cover could lead to decreases in UVery by up to 7%. (3) Reductions in reflectivity due to the melting of sea-ice in the Arctic would lead to decreases of UVery by up to 10%, while at the margins of the Antarctic the decreases would be smaller (2-3%). The melting of the sea-ice would expose the ocean surface formerly covered by ice to UV-B radiation up to 10 times stronger than before. (4) The expected improvement of air-quality and reductions of aerosols over the most populated areas of the northern hemisphere may result in 10-20% increases in UVery, except over China where even larger increases are projected. The projected aerosol effect for the southern hemisphere is generally very small. Aerosols are possibly the most important factor for future UV levels over heavily populated areas, but their projected effects are the most uncertain.

Ozone depletion and climate change: impacts on UV radiation.

The Montreal Protocol is working, but it will take several decades for ozone to return to 1980 levels. The atmospheric concentrations of ozone depleting substances are decreasing, and ozone column amounts are no longer decreasing. Mid-latitude ozone is expected to return to 1980 levels before mid-century, slightly earlier than predicted previously. However, the recovery rate will be slower at high latitudes. Springtime ozone depletion is expected to continue to occur at polar latitudes, especially in Antarctica, in the next few decades. Because of the success of the Protocol, increases in UV-B radiation have been small outside regions affected by the Antarctic ozone hole, and have been difficult to detect. There is a large variability in UV-B radiation due to factors other than ozone, such as clouds and aerosols. There are few long-term measurements available to confirm the increases that would have occurred as a result of ozone depletion. At mid-latitudes UV-B irradiances are currently only slightly greater than in 1980 (increases less than ~5%), but increases have been substantial at high and polar latitudes where ozone depletion has been larger. Without the Montreal Protocol, peak values of sunburning UV radiation could have been tripled by 2065 at mid-northern latitudes. This would have had serious consequences for the environment and for human health. There are strong interactions between ozone depletion and changes in climate induced by increasing greenhouse gases (GHGs). Ozone depletion affects climate, and climate change affects ozone. The successful implementation of the Montreal Protocol has had a marked effect on climate change. The calculated reduction in radiative forcing due to the phase-out of chlorofluorocarbons (CFCs) far exceeds that from the measures taken under the Kyoto protocol for the reduction of GHGs. Thus the phase-out of CFCs is currently tending to counteract the increases in surface temperature due to increased GHGs. The amount of stratospheric ozone can also be affected by the increases in the concentration of GHGs, which lead to decreased temperatures in the stratosphere and accelerated circulation patterns. These changes tend to decrease total ozone in the tropics and increase total ozone at mid and high latitudes. Changes in circulation induced by changes in ozone can also affect patterns of surface wind and rainfall. The projected changes in ozone and clouds may lead to large decreases in UV at high latitudes, where UV is already low; and to small increases at low latitudes, where it is already high. This could have important implications for health and ecosystems. Compared to 1980, UV-B irradiance towards the end of the 21st century is projected to be lower at mid to high latitudes by between 5 and 20% respectively, and higher by 2-3% in the low latitudes. However, these projections must be treated with caution because they also depend strongly on changes in cloud cover, air pollutants, and aerosols, all of which are influenced by climate change, and their future is uncertain. Strong interactions between ozone depletion and climate change and uncertainties in the measurements and models limit our confidence in predicting the future UV radiation. It is therefore important to improve our understanding of the processes involved, and to continue monitoring ozone and surface UV spectral irradiances both from the surface and from satellites so we can respond to unexpected changes in the future.

Transport impacts on atmosphere and climate: Aviation.

Aviation alters the composition of the atmosphere globally and can thus drive climate change and ozone depletion. The last major international assessment of these impacts was made by the Intergovernmental Panel on Climate Change (IPCC) in 1999. Here, a comprehensive updated assessment of aviation is provided. Scientific advances since the 1999 assessment have reduced key uncertainties, sharpening the quantitative evaluation, yet the basic conclusions remain the same. The climate impact of aviation is driven by long-term impacts from CO2 emissions and shorter-term impacts from non-CO2 emissions and effects, which include the emissions of water vapour, particles and nitrogen oxides (NO x ). The present-day radiative forcing from aviation (2005) is estimated to be 55 mW m-2 (excluding cirrus cloud enhancement), which represents some 3.5% (range 1.3-10%, 90% likelihood range) of current anthropogenic forcing, or 78 mW m-2 including cirrus cloud enhancement, representing 4.9% of current forcing (range 2-14%, 90% likelihood range). According to two SRES-compatible scenarios, future forcings may increase by factors of 3-4 over 2000 levels, in 2050. The effects of aviation emissions of CO2 on global mean surface temperature last for many hundreds of years (in common with other sources), whilst its non-CO2 effects on temperature last for decades. Much progress has been made in the last ten years on characterizing emissions, although major uncertainties remain over the nature of particles. Emissions of NO x result in production of ozone, a climate warming gas, and the reduction of ambient methane (a cooling effect) although the overall balance is warming, based upon current understanding. These NO x emissions from current subsonic aviation do not appear to deplete stratospheric ozone. Despite the progress made on modelling aviation's impacts on tropospheric chemistry, there remains a significant spread in model results. The knowledge of aviation's impacts on cloudiness has also improved: a limited number of studies have demonstrated an increase in cirrus cloud attributable to aviation although the magnitude varies: however, these trend analyses may be impacted by satellite artefacts. The effect of aviation particles on clouds (with and without contrails) may give rise to either a positive forcing or a negative forcing: the modelling and the underlying processes are highly uncertain, although the overall effect of contrails and enhanced cloudiness is considered to be a positive forcing and could be substantial, compared with other effects. The debate over quantification of aviation impacts has also progressed towards studying potential mitigation and the technological and atmospheric tradeoffs. Current studies are still relatively immature and more work is required to determine optimal technological development paths, which is an aspect that atmospheric science has much to contribute. In terms of alternative fuels, liquid hydrogen represents a possibility and may reduce some of aviation's impacts on climate if the fuel is produced in a carbon-neutral way: such fuel is unlikely to be utilized until a 'hydrogen economy' develops. The introduction of biofuels as a means of reducing CO2 impacts represents a future possibility. However, even over and above land-use concerns and greenhouse gas budget issues, aviation fuels require strict adherence to safety standards and thus require extra processing compared with biofuels destined for other sectors, where the uptake of such fuel may be more beneficial in the first instance.

Comparison of atmospheric spectral radiance measurements from five independently calibrated systems.

A variety of instruments have been developed over the past 50 years to measure spectral radiance in absolute units at UV and visible wavelengths with high spectral resolution. While there is considerable experience in the measurement of spectral irradiance, less emphasis has been given to the reliable measurement of spectral radiance from ground observations. We discuss the methodology and calibration procedures for five instruments capable of making such measurements. Four of these instruments are based on double monochromators that scan each wavelength in turn, and one is based on a single monochromator with a charged coupled device (CCD) allowing the recording of all wavelengths simultaneously. The measured spectral radiance deviates between 3% and about 35% depending on the instruments. The results are compared with radiative transfer calculations when the aerosol characteristics of the atmosphere are known.

Sorting vector producer cells for high transgene expression increases retroviral titer.

Vector producer cells are derived from helper cell lines expressing viral proteins that have been transduced to express a transgene-carrying retroviral genome. Vector producing cells express two relevant forms of RNA in their cytoplasm: vector RNA (vRNA) that is packaged as the actual gene transfer agent, and messenger RNA (mRNA) from which transgene is translated. Two premises underlie this study: (1) vRNA is limiting for virus production and (2) mRNA is proportional to vRNA. Together, these premises predict that transgene expression in the vector producing cells will be predictive of the viral titer from those cells. In this case, sorting the vector producing cells for high transgene expression should select for more virus production in vector producing cell supernatants. This prediction was supported, with a greater than fivefold benefit in viral titer. This demonstrates a rapid and simple method by which to obtain significantly increased viral titers from the same vector producing cell preparation.

Changes in biologically-active ultraviolet radiation reaching the Earth's surface.

The Montreal Protocol is working. Concentrations of major ozone-depleting substances in the atmosphere are now decreasing, and the decline in total column amounts seen in the 1980s and 1990s at mid-latitudes has not continued. In polar regions, there is much greater natural variability. Each spring, large ozone holes continue to occur in Antarctica and less severe regions of depleted ozone continue to occur in the Arctic. There is evidence that some of these changes are driven by changes in atmospheric circulation rather than being solely attributable to reductions in ozone-depleting substances, which may indicate a linkage to climate change. Global ozone is still lower than in the 1970s and a return to that state is not expected for several decades. As changes in ozone impinge directly on UV radiation, elevated UV radiation due to reduced ozone is expected to continue over that period. Long-term changes in UV-B due to ozone depletion are difficult to verify through direct measurement, but there is strong evidence that UV-B irradiance increased over the period of ozone depletion. At unpolluted sites in the southern hemisphere, there is some evidence that UV-B irradiance has diminished since the late 1990s. The availability and temporal extent of UV data have improved, and we are now able to evaluate the changes in recent times compared with those estimated since the late 1920s, when ozone measurements first became available. The increases in UV-B irradiance over the latter part of the 20th century have been larger than the natural variability. There is increased evidence that aerosols have a larger effect on surface UV-B radiation than previously thought. At some sites in the Northern Hemisphere, UV-B irradiance may continue to increase because of continuing reductions in aerosol extinctions since the 1990s. Interactions between ozone depletion and climate change are complex and can be mediated through changes in chemistry, radiation, and atmospheric circulation patterns. The changes can be in both directions: ozone changes can affect climate, and climate change can affect ozone. The observational evidence suggests that stratospheric ozone (and therefore UV-B) has responded relatively quickly to changes in ozone-depleting substances, implying that climate interactions have not delayed this process. Model calculations predict that at mid-latitudes a return of ozone to pre-1980 levels is expected by the mid 21st century. However, it may take a decade or two longer in polar regions. Climate change can also affect UV radiation through changes in cloudiness and albedo, without involving ozone and since temperature changes over the 21st century are likely to be about 5 times greater than in the past century. This is likely to have significant effects on future cloud, aerosol and surface reflectivity. Consequently, unless strong mitigation measures are undertaken with respect to climate change, profound effects on the biosphere and on the solar UV radiation received at the Earth's surface can be anticipated. The future remains uncertain. Ozone is expected to increase slowly over the decades ahead, but it is not known whether ozone will return to higher levels, or lower levels, than those present prior to the onset of ozone depletion in the 1970s. There is even greater uncertainty about future UV radiation, since it will be additionally influenced by changes in aerosols and clouds.

A shift to a peripheral Th2-type cytokine pattern during the carcinogenesis of cervical cancer becomes manifest in CIN III lesions.

BACKGROUND: A shifted balance between T helper 1 (Th1)-type and Th2-type cytokines has been hypothesised in cervical dysplasia. AIMS: To evaluate possible deregulation of the cytokine network by estimating the expression of peripheral cytokines in different stages of cervical disease and in relation to the presence or absence of high risk human papillomavirus (HR-HPV). METHODS: Twenty one HR-HPV positive women with high grade cervical intraepithelial neoplasia (CIN II-III) and 12 patients with invasive cervical carcinoma formed the study groups. Two control groups consisted of 10 HR-HPV positive and 11 HR-HPV negative women without CIN. Differences in leucocyte subgroups were evaluated by a differential leucocyte count. Plasma concentrations of tumour necrosis factor alpha (TNFalpha), TNFalpha receptors TNFRI and TNFRII, interferon gamma (IFNgamma), interleukin 2 (IL-2), IL-12, IL-4, and IL-10 were determined by enzyme linked immunosorbent assays. RESULTS: Leucocyte counts in patients with CIN III and carcinoma were significantly higher than in controls. Plasma IFNgamma concentrations were significantly lower in patients with CIN III and carcinoma than in women with CIN II or controls. Plasma concentrations of IL-12, IL-2, IL-4, and TNFalpha did not differ significantly between groups, but significantly lower plasma concentrations of TNFRII were found in CIN III and carcinoma compared with CIN II. IL-10 was detected with increased frequency in the plasma of patients with CIN III and carcinoma. CONCLUSIONS: These results indicate that a shift to a Th2-type cytokine pattern during the carcinogenesis of cervical cancer occurs in women with CIN III lesions.

HPV testing and monitoring of women after treatment of CIN 3: review of the literature and meta-analysis.

According to the current guidelines in most western countries, women treated for cervical intraepithelial neoplasia grade 3 (CIN 3) are followed for at least 2 years after treatment by cytology.High-risk human papillomavirus (hrHPV) infections are necessary for the development and maintenance of CIN 3. HrHPV testing could be used to improve monitoring of women treated for CIN 3. This has prompted numerous studies for the implementation of hrHPV testing in monitoring of women treated for CIN 3. Included in this review are 20 studies, published between 1996 and 2003, comparing hrHPV testing with either resection margins or cervical cytology to predict recurrent/residual disease, and 11 of them could be used in a meta-analysis. In the meta-analysis of the 11 studies, the negative predictive value (NPV) for recurrent/residual disease of hrHPV testing was 98% (95% CI 97-99%), that of resection margins 91% (95% CI 87-94%), and that of cervical cytology 93% (95% CI 90-95%). When hrHPV testing was performed in conjunction with cytology, the sensitivity was 96% (95% CI 89-99%), specificity was 81% (95% CI 77-84%), the associated positive predictive value (PPV) was 46% (95% CI 38-54%), and the NPV was 99% (95% CI 98-100%). Combined hrHPV and cytology testing yielded the best test characteristics. We propose to include hrHPV testing in conjunction with cytology for monitoring women treated for CIN 3. Some follow-up visits for women testing negative for both hrHPV and cytology can be skipped. In western countries, this could mean that for women double negative at 6 months, retesting at 12 months should be skipped while keeping the 24-month follow-up visit.

[Follow up after an abnormal pap smear: time interval acceptable, nature of follow up leaves room for improvement]. / Vervolgonderzoek na een afwijkend uitstrijkje: tijdsinterval acceptabel, aard van het vervolgonderzoek vaak niet.

OBJECTIVE: To investigate whether the interval between an abnormal Pap smear and follow-up is too long and whether the guidelines for histological follow-up after an abnormal Pap smear are being followed. DESIGN: Descriptive. METHOD: Data on all Pap smears of a minimum Pap class 3a (moderate dysplasia) from the national cervical-cancer screening programme in the Rotterdam area of the Netherlands were acquired from the Pathological Anatomical National Automated Archive (PALGA). The test results from each woman were arranged chronologically and the nature of the follow-up cervical examinations (cytological and histological) was recorded. The observation period was 360 days. The average interval in days between Pap smear and follow-up as well as the nature of the follow-up were analysed. RESULTS: In total, data on 156 women were analysed. In 93% of women follow-up was done during our observation period. The average interval was 60 days. In 80% of the women follow-up took place within 3 months and in 90% within 6 months. In 32% of women in the follow-up group the Pap smear was repeated at their first follow-up visit and in the remaining cases, a histological examination was performed according to the guidelines. In 7% of cases no cytological or histological follow-up at all took place within the year. CONCLUSION: The average interval between an abnormal Pap smear and follow-up is acceptable because of the slow natural course of cervical carcinoma. Attention should be focused on the incorrect repetition of the cytological test and on the fact that in a number of cases no follow-up at all is done within 1 year.

[Diagnostic image (142). A woman with persistent dyspareunia and vaginal discharge. Vaginal adenosis]. / Diagnose in beeld (142). Een vrouw met persisterende dyspareunie en fluor. Vaginale adenose.

In a 30-year-old woman with persistent dyspareunia and vaginal discharge additional investigations revealed a vaginal adenosis.