Economic appraisal of the public control and prevention strategy against the 2010 West Nile Virus outbreak in Central Macedonia, Greece.

OBJECTIVES: The aim of the present paper is to evaluate the economic efficiency of the public control and prevention strategies to tackle the 2010 West Nile Virus (WNV) outbreak in the Region of Central Macedonia, Greece. Efficiency is examined on the basis of the public prevention costs incurred and their potential in justifying the costs arising from health and nuisance impacts in the succeeding years. STUDY DESIGN: Economic appraisal of public health management interventions. METHODS: Prevention and control cost categories including control programmes, contingency planning and blood safety testing, are analyzed based on market prices. A separate cost of illness approach is conducted for the estimation of medical costs and productivity losses from 2010 to 2013 and for the calculation of averted health impacts. The averted mosquito nuisance costs to households are estimated on the basis of a contingent valuation study. Based on these findings, a limited cost-benefit analysis is employed in order to evaluate the economic efficiency of these strategies in 2010-2013. RESULTS: Results indicate that cost of illness and prevention costs fell significantly in the years following the 2010 outbreak, also as a result of the epidemic coming under control. According to the contingent valuation survey, the annual average willingness to pay to eliminate the mosquito problem in the study area ranged between 22 and 27 € per household. Cost-benefit analysis indicates that the aggregate benefit of implementing the previous 3-year strategy creates a net socio-economic benefit in 2013. However the spread of the WNV epidemic and the overall socio-economic consequences, had the various costs not been employed, remain unpredictable and extremely difficult to calculate. CONCLUSIONS: The application of a post epidemic strategy appears to be of utmost importance for public health safety. An updated well designed survey is needed for a more precise definition of the optimum prevention policies and levels and for the establishment of the various cost/benefit parameters.

Epidemiological, clinical, and virological characteristics of women with genital warts in Greece.

This is a prospective study of the epidemiological, clinical, and virological characteristics of cases of genital warts in a Greek University Hospital. The women completed a questionnaire regarding their medical and sexual history and underwent cervical cytology, HPV DNA typing, mRNA testing, colposcopy, Chlamydia testing, and proctoscopy. Univariate and multivariate analyses were performed. The most commonly detected types were type 6 (36.1%) and 16 (24.3%). E6/E7 mRNA testing was positive in 21.5%. Concurrent cervical intraepithelial neoplasia grade 2 or worse was found in 11.1% and intra-anal warts in 10.4%. For chlamydial infection the number of sexual partners was a significant predictor. Women with warts infected with types 6 and 11 constituted only 37.5% of the total. This could have a negative effect on the efficacy of vaccination in reducing the incidence of the disease. Based on the present findings the authors recommend cytology and colposcopy for all women with genital warts.

Evaluation of the repellent effects of Nepeta parnassica extract, essential oil, and its major nepetalactone metabolite against mosquitoes.

The dichloromethane-methanol extract, the essential oil obtained by hydrodistillation from Nepeta parnassica, and the isolated 4aα,7α,7aß-nepetalactone were evaluated for their repellent effect against the mosquitoes Aedes (Stegomyia) cretinus Edwards and Culex pipiens pipiens biotype molestus Forskål. The chemical analysis of N. parnassica essential oil, dominated by oxygenated monoterpenes (87 %), revealed 4aα,7α,7aß-nepetalactone (36.8%), 1,8-cineole (25.5%), and 4aα,7ß,7aß-nepetalactone (11.1%) as the major constituents. The results of the insect bioassays showed that the essential oil and the dichloromethane-methanol extract of N. parnassica were very active against Aedes cretinus for up to 3 h and against Culex pipiens for up to 2 h post application. The isolated 4aα,7α,7aß-nepetalactone showed very high mosquito repellency for periods of at least 2 h against both species.

Early-stage cervical carcinoma: the role of multidetector CT in correlation with histopathological findings.

The objective of this retrospective study was to assess the diagnostic performance of multidetector CT (MDCT) in staging patients with surgical-pathological proven early-stage cervical carcinoma. A total of 22 women were referred for preoperative staging by MDCT, on a 16-row CT scanner. The protocol included scanning of the abdomen during the portal phase using a detector collimation of 16 × 0.75 mm and a pitch of 1.2. The evaluated parameters were: tumour detection, tumour maximal diameter, tumour extension to the uterine body and/or the vagina, parametrial invasion and presence of pelvic lymph node metastases. CT stage was assigned for each cervical carcinoma. The surgical-pathological stage was assigned on the basis of the operative findings and the histology report. The overall accuracy of MDCT in detecting and staging primary cervical carcinoma was 86% and 86%, respectively. Our results showed good diagnostic performance of MDCT in the detection and local staging of early-stage cervical carcinoma.

Evaluation of naturally occurring curcuminoids and related compounds against mosquito larvae.

The three curcuminoid components commonly isolated from Curcuma longa, curcumin (1), demethoxycurcumin (2), and bis-demethoxycurcumin (3) were separated and isolated from a commercially available turmeric extract product in high purity and sufficient amounts. Three more derivatives of curcumin, the di-O-demethylcurcumin (4), di-O-methylcurcumin (5) and the di-O-acetylcurcumin (6) were also synthesized and characterized. All six compounds were evaluated for their larvicidal effect against the mosquito Culex pipiens. Curcumin (1) exhibited highly potent larvicidal activity with LC(50) value of 19.07mgL(-1). Moreover, di-O-demethylcurcumin (4), was found to be equally active with LC(50) value of 12.42mgL(-1). Based on the LC(90) values of the two compounds, di-O-demethylcurcumin (4) was the most active of all, resulting in an LC(90) value of 29.40mgL(-1), almost half of the LC(90) value 61.63mgL(-1) found for compound 1. The rest of the compounds were inactive at concentrations even as high as 150mgL(-1) indicating a dependence of the larvicidal activity upon the substitution patent and the presence of aromatic hydroxyl and methoxy moieties. These results show for the first time the potential of this valuable natural product regarding its use as vector control agent.

Apparent diffusion coefficient values of the normal uterus: Interindividual variations during menstrual cycle.

OBJECTIVES: To assess the apparent diffusion coefficient (ADC) changes of the normal uterine zones among reproductive women during the menstrual cycle. METHODS: The study included 101 women of reproductive age, each with regular cycle and normal endometrium/myometrium, as proved on histopathology or MR imaging examination. Diffusion-weighted (DW) imaging was performed along the axial plane, using a single shot, multi-slice spin-echo planar diffusion pulse sequence and b-values of 0 and 800s/mm(2). The mean and standard deviation of the ADC values of normal endometrium/myometrium were calculated for menstrual, proliferative and secretory phase. Analysis of variance followed by the least significant difference test was used for statistical analysis. RESULTS: The ADC values of the endometrium were different in the three phases of the menstrual cycle (menstrual phase: 1.25±0.27; proliferative phase: 1.39±0.20; secretory phase: 1.50±0.18) (F: 9.64, p: 0.00). Statistical significant difference was observed among all groups (p<0.05). The ADC values of the normal myometrium were different in the three phases of the menstrual cycle (menstrual phase: 1.91±0.35; proliferative phase: 1.72±0.27; secretory phase: 1.87±0.28) (F: 3.60, p: 0.03). Statistical significant difference was observed between menstrual and proliferative phase and between proliferative and secretory phase (p<0.05). No significant difference was noted between menstrual and secretory phase (p>0.05). CONCLUSIONS: A wide variation of ADC values of normal endometrium and myometrium is observed during different phases of the menstrual cycle.

Essential oils of indigenous in Greece six Juniperus taxa: chemical composition and larvicidal activity against the West Nile virus vector Culex pipiens.

The chemical composition of 14 essential oils (EOs), obtained from various parts (leaves, fruits, wood) of the six indigenous in Greece Juniperus family taxa, was determined by GC and GC/MS analysis. The insecticidal properties of these EOs were evaluated against Culex pipiens L. larvae of 3rd and early 4th instars, in order to delineate the relationship between the phytochemical content of the EOs and their larvicidal activities. The analytical data indicated that the EOs mainly consisted of monoterpenes, mostly cyclic and only occasionally aliphatic, and to a lesser percent, of diterpenes. The larvicidal bioassays against C. pipiens larvae revealed that the most active EO was derived from the wood of Juniperus drupacea and contains mainly non-oxygenated monoterpenes and a significant amount of diterpenes, displaying the highest chemodiversity. Its initial LC(50) value was 26.47 mg L(-1). On the contrary, the EO isolated from J. phoenicea berries, which consisted of monoterpenes (non-oxygenated, cyclic), was the less active displaying an LC(50) value of 96.69 mg L(-1). In respect to the contained phytochemicals, myrcene was assayed as the most toxic, displaying an LC(50) value of 33.83 mg L(-1), while the four isomers of pinene abundant in all EOs were less active exhibiting LC(50) values ranging from 70.40 to 94.88 mg L(-1). Results herein reveal that the EOs isolated from the studied Juniperus family taxa represent an inexpensive source of natural mosquito control mixtures.

Women's knowledge and utilization of gynecological cancer prevention services in the Northwest of Greece.

PURPOSE OF INVESTIGATION: In Greece an organized cervical or breast cancer screening program does not exist and the population coverage is unknown. METHODS: Women of all ages completed a questionnaire, which assessed women's awareness of and participation in breast and cervical screening and human papillomavirus (HPV) vaccination. The women were randomly approached in public areas. RESULTS: 1,012 women completed the questionnaire. 52% of the women over 39 years old had undergone mammography in the last year and 76% of the women over 20 years old had a cervical smear test within the last three years in an opportunistic basis. In addition, the likelihood of having regular mammograms was positively associated with the likelihood of having regular cervical smears. Fifty percent of the responders did not identify HPV as the cause of cervical cancer and 38% were not aware of the HPV vaccine. From the women aged 16 to 28 years old, 11% had been vaccinated against HPV and an additional 23% intended to have the vaccine in the next six months. CONCLUSION: Knowledge and utilization of mammography and cervical screening was quite satisfactory, although HPV vaccination coverage was low. Preventive services could be improved through the development of a plan for the information of the public and the distribution of the HPV vaccine.

Alterations in human papillomavirus-related biomarkers after treatment of cervical intraepithelial neoplasia.

OBJECTIVE: This study aims to assess the alterations in various HPV-related biomarkers 6 months post-treatment and how these relate to various risk factors and individual characteristics; their role for the prediction of treatment failure was also evaluated. DESIGN: Prospective observational study. POPULATION: Women planning to undergo treatment for cervical intraepithelial neoplasia. INTERVENTION: A liquid-based cytology sample was taken pre-operatively. This was tested for HPV genotyping, Nucleic Acid Sequence Based Amplification, flow cytometric evaluation and p16 immunostaining. A repeat LBC sample was obtained 6 months post-treatment and was tested for the same biomarkers. OUTCOMES: The alterations of the biomarkers 6 months post-treatment were recorded. Their relation to individual characteristics and risk factors (age, smoking, sexual history, use of condom, CIN grade, excision margin status, crypt involvement) as well as their role for the prediction of residual/recurrent disease were assessed. ANALYSIS: The accuracy parameters (sensitivity, specificity, positive and negative predictive value and the likelihood ratios) of each biomarker for the prediction of recurrent/residual CIN were calculated. RESULTS: A total of 190 women were recruited. All biomarkers had significantly higher negativity rates post-treatment compared to pre-treatment ones. Multivariate analysis demonstrated that consistent condom use post-treatment significantly reduces the high-risk HPV positivity rates in comparison to no use (OR=0.18; 95% CI: 0.09-0.38). Sensitivity and specificity for all high risk HPV DNA testing were 0.5/0.62, respectively; the relevant values for only type 16 or 18 DNA typing were 0.5/0.92, for NASBA 0.5/0.94, for flow 0.5/0.85 and for p16 0.25/0.93. CONCLUSION: CIN treatment reduces positivity for all HPV-related biomarkers. Consistent condom use significantly reduces high-risk HPV positivity rates. More cases of treatment failures are required in order to specify whether different combinations of HPV-related biomarkers could enhance the accuracy of follow up, possibly in the form of a Scoring System that could allow tailored post-treatment surveillance.

High-risk human papillomavirus DNA test and p16(INK4a) in the triage of LSIL: a prospective diagnostic study.

OBJECTIVE: The detection of high-grade cervical intraepithelial neoplasia (CIN) amongst patients with low-grade cytology (LSIL) is challenging. This study evaluated the role of high-risk HPV (HR-HPV) DNA test and p16(INK4a) immunostaining in identifying women with LSIL cytology at risk of harboring CIN2 or worse (CIN2+) and the role of p16(INK4a) in the triage of a population of HR-HPV positive LSIL. METHODS: We conducted a prospective study including women with LSIL cytology. Detection of HR-HPV was carried out by means of a polymerase chain reaction based assay. p16(INK4a) immunostaining was performed using the Dako CINtec cytology kit. All patients had colposcopically directed punch biopsies or large loop excision of the transformation zone of the cervix. The endpoint was detection of a biopsy-confirmed CIN2+. RESULTS: A series of 126 women with LSIL cytology were included. HR-HPV test had sensitivity 75% and specificity 64% for an endpoint of CIN2+. p16(INK4a) had significantly higher specificity of 89% (p=0.0000) but low sensitivity of 42%. The role of p16(INK4a) immunostaining in the triage of LSIL positive for HR-HPV was also evaluated. p16(INK4a) triage had 70% positive predictive value (PPV); however, this was not significantly higher than the PPV (56%) of HR-HPV test alone (p=0.4). CONCLUSIONS: The results indicate that HR-HPV or p16(INK4a) cannot be used as solitary markers for the assessment of LSIL. The addition of p16(INK4a) immunostaining led to an increase in HR-HPV specificity; however, the biomarker needs to be assessed further to establish its role as an adjunct test in the triage of LSIL.

Clinical management of HPV-related disease of the lower genital tract.

Cytology remains the mainstay for cervical screening. The need to achieve effective management, limit complications, and preserve reproductive function led to the popularity of local treatment. Although the cure rates for ablative and excisional methods are similar, the excisional method provides a more reliable histopathological diagnosis. Recent evidence revealed increased perinatal morbidity after treatment that appears to be related to the proportion of cervix removed. The human papillomavirus (HPV) DNA test appears to enhance the detection of disease in primary screening, in the triage of minor cytological abnormalities, and in follow-up. Further research on the clinical application of a scoring system is ongoing. The vaccines are now available and appear to be safe, well tolerated, and highly efficacious in HPV naive women. A synergy of vaccination and screening will be required. Treatment for early cervical cancer is increasingly shifting toward more fertility-sparing surgical techniques. Careful selection of patients is essential.

p16(INK4a) immunostaining in cytological and histological specimens from the uterine cervix: a systematic review and meta-analysis.

BACKGROUND: P16(INK4a) is a biomarker for transforming HPV infections that could act as an adjunct to current cytological and histological assessment of cervical smears and biopsies, allowing the identification of those women with ambiguous results that require referral to colposcopy and potentially treatment. MATERIAL AND METHODS: We conducted a systematic review of all studies that evaluated the use of p16(INK4a) in cytological or histological specimens from the uterine cervix. We also estimated the mean proportion of samples that were positive for p16(INK4a) in cytology and histology, stratified by the grade of the lesion. RESULTS: Sixty-one studies were included. The proportion of cervical smears overexpressing p16(INK4a) increased with the severity of cytological abnormality. Among normal smears, only 12% (95% CI: 7-17%) were positive for the biomarker compared to 45% of ASCUS and LSIL (95% CI: 35-54% and 37-57%, respectively) and 89% of HSIL smears (95% CI: 84-95%). Similarly, in histology only 2% of normal biopsies (95% CI: 0.4-30%) and 38% of CIN1 (95% CI: 23-53%) showed diffuse staining for p16(INK4a) compared to 68% of CIN2 (95% CI: 44-92%) and 82% of CIN3 (95% CI: 72-92%). CONCLUSION: Although there is good evidence that p16(INK4a) immunostaining correlates with the severity of cytological/histological abnormalities, the reproducibility is limited due to insufficiently standardized interpretation of the immunostaining. Therefore, a consensus needs to be reached regarding the evaluation of p16(INK4a) staining and the biomarker needs to be assessed in various clinical settings addressing specific clinical questions.

Chemical composition and larvicidal activity of essential oils from six Apiaceae family taxa against the West Nile virus vector Culex pipiens.

The chemical compositions of essential oils (EOs) obtained from six different taxa of the Apiaceae family, Apioideae subfamily, belonging to three tribes and six different genuses were determined by gas chromatography and gas chromatography-mass spectrometry analyses. All examined plants grow naturally in different habitats throughout Greece. The insecticidal properties of these EOs were evaluated against Culex pipiens L. larvae of third and early fourth instars in order to delineate the relationship between the EOs phytochemical content and larvicidal activity. The analytical data indicated that the EOs are mainly consisted of monoterpenes, mostly cyclic and only occasionally aliphatic. The larvicidal bioassay results indicated that the oil of Oenanthe pimpinelloides L., which contains mainly nonoxygenated monoterpenes, possesses the highest activity against Cx. pipiens larvae, displaying a LC(50) value of 40.26 mg/L. On the contrary, the EO of Elaeoselinum asclepium (L.) Bertol, which is consisted of pinenes and oxygenated monoterpenes, was the less active (LC(50) value of 96.96 mg/L). These results reveal that the nonoxygenated monoterpenes possess potent insecticidal activities against Cx. pipiens L. and the EO of O. pimpinelloides L. represents an inexpensive source of natural pest control mixture.

Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis.

OBJECTIVE: To assess the relative risk of perinatal mortality, severe preterm delivery, and low birth weight associated with previous treatment for precursors of cervical cancer. DATA SOURCES: Medline and Embase citation tracking from January 1960 to December 2007. Selection criteria Eligible studies had data on severe pregnancy outcomes for women with and without previous treatment for cervical intraepithelial neoplasia. Considered outcomes were perinatal mortality, severe preterm delivery (<32/34 weeks), extreme preterm delivery (<28/30 weeks), and low birth weight (<2000 g, <1500 g, and <1000 g). Excisional and ablative treatment procedures were distinguished. RESULTS: One prospective cohort and 19 retrospective studies were retrieved. Cold knife conisation was associated with a significantly increased risk of perinatal mortality (relative risk 2.87, 95% confidence interval 1.42 to 5.81) and a significantly higher risk of severe preterm delivery (2.78, 1.72 to 4.51), extreme preterm delivery (5.33, 1.63 to 17.40), and low birth weight of <2000 g (2.86, 1.37 to 5.97). Laser conisation, described in only one study, was also followed by a significantly increased chance of low birth weight of <2000 g and <1500 g. Large loop excision of the transformation zone and ablative treatment with cryotherapy or laser were not associated with a significantly increased risk of serious adverse pregnancy outcomes. Ablation by radical diathermy was associated with a significantly higher frequency of perinatal mortality, severe and extreme preterm delivery, and low birth weight below 2000 g or 1500 g. CONCLUSIONS: In the treatment of cervical intraepithelial neoplasia, cold knife conisation and probably both laser conisation and radical diathermy are associated with an increased risk of subsequent perinatal mortality and other serious pregnancy outcomes, unlike laser ablation and cryotherapy. Large loop excision of the transformation zone cannot be considered as completely free of adverse outcomes.

Management of minor cervical cytological abnormalities: a systematic review and a meta-analysis of the literature.

BACKGROUND: A significant number of women are diagnosed with a low grade cytological abnormality on cervical screening. Many authorities recommend surveillance as spontaneous regression might occur. However, protracted attendance for cytological follow-up decreases with time and might put some women at risk of developing invasive disease. The aim of this review was to assess management options for women with minor cervical disease. METHODS: An electronic literature search was conducted. All randomised controlled studies comparing immediate colposcopy to cytological surveillance in women with cervical atypia/borderline nuclear changes or low-grade lesions were included. The main outcomes studied were the default rates from the colposcopy clinic and the histological status of biopsies within immediate management protocols compared to biopsies taken on completion of surveillance. Pooled relative risks and 95% confidence intervals were calculated using a random-effect model and inter-study heterogeneity was assessed with Cochrane's Q-test. RESULTS: Three randomised controlled trials identified from the literature search with different surveillance periods were combined. The analysis revealed that compliance with follow-up declines over time and reaches significance at the end of 24 months of surveillance (RR: 74.10 [10.36, 529.79]). There was a significantly higher incidence of HPV and CIN 1 in those women referred to immediate colposcopy/treatment compared to those at the end of 24 months surveillance period (32% vs 21%) (RR 1.49, 95% CI 1.17-1.90) and (21% vs 8%) (RR 2.58, 95% CI 1.69-3.94), respectively, possibly explained by spontaneous regression of clinically non-important lesions. Finally, there was no significant difference in the incidence of CIN2 or worse at initial colposcopy compared with the observation group (24 months) (RR 1.72, 95% CI 0.85-3.48). CONCLUSION: Cytological surveillance puts women at risk as many show poor compliance and such women might have occult high grade abnormalities. A general policy should be immediate colposcopy for all women after a single low grade cervical smear.

The up-to-date evidence on colposcopy practice and treatment of cervical intraepithelial neoplasia: the Cochrane colposcopy & cervical cytopathology collaborative group (C5 group) approach.

This overview presents the up-to-date evidence on colposcopy practice and other diagnostic modalities such as HPV DNA test and cytology for cervical intraepithelial neoplasia (CIN). Current evidence supports the use of colposcopy for the detection of intraepithelial lesions as a second line tool. CIN treatment involves either excisional or destructive techniques, usually performed under local anesthesia. Although a debate exists about the most efficient approach, the currently available evidence reveals no differences in efficacy among the available conservative methods of treatment. New evidence supports treatment by destructive rather than excisional techniques, at least for low grade lesions in women wishing future childbearing, as they appear to have no apparent pregnancy-related morbidity. Treatment failures rates might increase in cases of involved excision margins, older age or glandular involvement. There is no worldwide consensus on the optimal follow-up policy, interventions or frequency in surveillance after treatment. HPV DNA test combined with either colposcopy or cytology is a promising combination for the early detection of treatment failures due to residual disease. Existing guidelines should probably be updated incorporating the new information emerged from recently published work.

Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis.

BACKGROUND: Conservative methods to treat cervical intraepithelial neoplasia and microinvasive cervical cancer are commonly used in young women because of the advent of effective screening programmes. In a meta-analysis, we investigated the effect of these procedures on subsequent fertility and pregnancy outcomes. METHODS: We searched for studies in MEDLINE and EMBASE and classified them by the conservative method used and the outcome measure studied regarding both fertility and pregnancy. Pooled relative risks and 95% CIs were calculated with a random-effects model and interstudy heterogeneity was assessed with Cochrane's Q test. FINDINGS: We identified 27 studies. Cold knife conisation was significantly associated with preterm delivery (<37 weeks; relative risk 2.59, 95% CI 1.80-3.72, 100/704 [14%] vs 1494/27 674 [5%]), low birthweight (<2500 g; 2.53, 1.19-5.36, 32/261 [12%] vs 905/13 229 [7%]), and caesarean section (3.17, 1.07-9.40, 31/350 [9%] vs 22/670 [3%]). Large loop excision of the transformation zone (LLETZ) was also significantly associated with preterm delivery (1.70, 1.24-2.35, 156/1402 [11%] vs 120/1739 [7%]), low birthweight (1.82, 1.09-3.06, 77/996 [8%] vs 49/1192 [4%]), and premature rupture of the membranes (2.69, 1.62-4.46, 48/905 [5%] vs 22/1038 [2%]). Similar but marginally non-significant adverse effects were recorded for laser conisation (preterm delivery 1.71, 0.93-3.14). We did not detect significantly increased risks for obstetric outcomes after laser ablation. Although severe outcomes such as admission to a neonatal intensive care unit or perinatal mortality showed adverse trends, these changes were not significant. INTERPRETATION: All the excisional procedures to treat cervical intraepithelial neoplasia present similar pregnancy-related morbidity without apparent neonatal morbidity. Caution in the treatment of young women with mild cervical abnormalities should be recommended. Clinicians now have the evidence base to counsel women appropriately.

Ovarian cancer screening.

PURPOSE: This review presents the current knowledge on ovarian cancer screening (OCS) together with a cumulative evaluation of the efficacy across diverse screening approaches based on up-to-date results. MATERIALS AND METHODS: An electronic literature search was conducted targeting reports on the effectiveness of the various screening strategies. RESULTS: Twenty-two prospective studies, 18 cohorts and 4 randomised control trials (RCTs) were retrieved. Where possible, sensitivity, specificity and predictive values, as well as the number needed to treat for each cancer (NNT) and each stage I disease [NNT (I)] detected are reported. CONCLUSION: The multimodal approach that incorporates CA125 as a primary and ultrasound as a secondary test appears to be superior to other strategies. However, the conclusive end-point that would provide the acceptable level of evidence for the introduction of screening should be a reduction in mortality. Up-to-date, there is no such evidence to justify this.

An observational study of women with positive HPV-DNA tests and normal cytology and colposcopy.

PURPOSE: High risk human papillomaviruses (HPV) are implicated in the aetiology of malignant cervical disease. The usefulness of HPV DNA tests in identifying women at risk of cervical cancer as an adjunct to cervical cytology is under evaluation. PATIENTS AND METHODS: This is a retrospective analysis of 47 women positive for high risk HPV but with negative cytology and negative colposcopy at the start of the study. Women were observed for three years or more (in 96% cases) using six-monthly combined HPV DNA tests, cytological and colposcopic evaluation. RESULTS: At the end of follow-up, 29/47 (62%) women were still positive for high risk HPV, 45/47 (96%) women had normal cytology and 47/47 (100%) women continued to have normal colposcopy. CONCLUSIONS: Normal colposcopy has an excellent negative predictive value for HPV positive women with normal cytology. These women can be safely screened cytologically on a three-yearly basis.

Is it now time to evaluate the true accuracy of cervical cytology screening? A review of the literature.

The incidence of and mortality from cervical invasive carcinoma have decreased over the last 30 years in the developed world, a fact which has been attributed mainly to the implementation of cervical cytology screening programmes (Papanicolaou test). The accuracy of this screening has been questioned because of false negative reports, thus other technologies have been proposed. There are only 12 studies evaluating cytology screening in low prevalence populations. In these studies the specificity appears to be high (85-100%) but the sensitivity estimates are variable and generally much lower (22-99%). Sensitivity is increased if lower thresholds of disease are used. Sampling or laboratory errors are important causes of false negative reports. Cytological cervical screening does not demonstrate the characteristics of an optimal screening test since it is relatively insensitive to the presence of disease although highly specific. The true screening accuracy of cytology needs to be assessed so that we can introduce strategies to improve smear taking and interpretation.