Sustainable Earnings among Immigrants, and the Role of Health Status for Self-Sufficiency: A 10-Year Follow-Up Study of Labour Immigrants and Refugees to Sweden 2000-2006.

This study aimed to investigate economic self-sufficiency for immigrants, and how health status affected self-sufficiency. The proportion of self-sufficiency during years 1-10 after receiving a residence permit is presented for all non-European labour immigrants (n = 1259) and refugees (n = 23,859), aged 18-54, who immigrated to Sweden 2000-2006, and compared to a control group of Swedish-born (n = 144,745). The risk of not being self-sufficient in year 10 was analysed with Cox regression models, and the results are presented as hazard ratios (HRs) with 95% confidence intervals (CIs). Moreover, the impact on the self-sufficiency of having a diagnosis from specialised health care during the first five years in Sweden was analysed. The results showed that half of the refugees and three-quarters of the labour immigrants were self-sufficient 10 years after residency. The adjusted risk of not being self-sufficient at year 10 was 80% higher among labour immigrants (HR = 1.8; CI = 1.6-2.0) and more than two-fold among refugees (HR = 2.7; CI = 2.6-2.8) compared to the Swedish-born. Having a diagnosis from specialised health care during the first five years in Sweden had an impact on self-sufficiency in all groups; however, the impact of having a diagnosis did not differ between refugees and Swedish-born. Measures must be taken to increase immigrants' work participation.

Healthy migrant effect in the Swedish context: a register-based, longitudinal cohort study.

OBJECTIVES: Studies have found a 'healthy-migrant effect' (HME) among arriving migrants, that is, a better health status compared with others in the home country, but also in comparison with the population in the host country. The aims were to investigate whether the HME hypothesis is applicable to the Swedish context, that is, if health outcomes differed between a group of mainly labour migrants (Western migrants) and a group of mainly refugee/family reunion migrants (non-Western migrants) compared with the native Swedish population, and if there were any correlations between labour market attachment (LMA) and these health outcomes. DESIGN: Register-based, longitudinal cohort study. PARTICIPANTS: The cohort was defined on 31 December 1990 and consisted of all migrants aged 18-47 years who arrived in Sweden in 1985-1990 (n=74 954) and a reference population of native Swedes (n=1 405 047) in the same age span. They were followed for three consecutive 6-year periods (1991-1996, 1997-2002 and 2003-2008) and were assessed for five measures of health: hospitalisation for cardiovascular and psychiatric disorders, mortality, disability pension, and sick leave. RESULTS: Western migrants had, compared with native Swedes, lower or equal HRs for all health measures during all time periods, while non-Western migrants displayed higher or equal HRs for all health measures, except for mortality, during all time periods. Age, educational level, occupation and LMA explained part of the difference between migrants and native Swedes. High LMA was associated with higher HRs for cardiovascular disorders among Western migrants, higher HRs of psychiatric disorders among non-Western migrants and higher HRs of mortality among both migrant groups compared with native Swedes. CONCLUSIONS: There were indications of a HME among Western migrants, while less proof of a HME among non-Western migrants. Stratification for LMA and different migrant categories showed some interesting differences, and measurements of the HME may be inconclusive if not stratified by migrant category or other relevant variables.

Human responses in heat - comparison of the Predicted Heat Strain and the Fiala multi-node model for a case of intermittent work.

Two mathematical models of human thermal regulation include the rational Predicted Heat Strain (PHS) and the thermophysiological model by Fiala. The approaches of the models are different, however, they both aim at providing predictions of the thermophysiological responses to thermal environments of an average person. The aim of this study was to compare and analyze predictions of the two models against experimental data. The analysis also includes a gender comparison. The experimental data comprised of ten participants (5 males, 5 females, average anthropometric values were used as input) conducting an intermittent protocol of rotating tasks (cycling, stacking, stepping and arm crank) of moderate metabolic activities (134-291W/m2) with breaks in-between in a controlled environmental condition (34°C, 60% RH). The validation consisted of the predictions' comparison against experimental data from 2.5h of data of rectal temperature and mean skin temperature based on contact thermometry from four body locations. The PHS model over-predicted rectal temperatures during the first activity for males and the cooling effectiveness of sweat in the recovery periods, for both males and females. As a result, the PHS simulation underestimated the thermal strain in this context. The Fiala model accurately predicted the rectal temperature throughout the exposure. The fluctuation of the experimental mean skin temperature was not reflected in any of the models. However, the PHS simulation model showed better agreement than the Fiala model. As both models predicted responses more accurately for males than females, we suggest that in future development of the models it is important to take this result into account. The paper further discusses possible sources of the observed discrepancies and concludes with some suggestions for modifications.

Exposure to different lengths of sick leave and subsequent work absence among young adults.

BACKGROUND: Sweden has a public and easily accessible sickness insurance. Research shows, however, downsides to taking sick leave. Both short and longer periods of sick leave have been seen to increase the risk for subsequent work absence. The aim of this study was to investigate whether there was an association between sick leave claimed in 1993 and work absence in the subsequent 15 years, i.e. up to 2008. A further aim was to explore differences in this relation with regard to gender, origin and educational level at baseline. METHODS: Our cohort consisted of all immigrants aged 21-25 years in Sweden in 1993 and a control group of native Swedes in the same age group. RESULTS: Subsequent work absence increased from 313 days among persons with no days of claimed sick leave in 1993 to 567 days among persons with 1-7 days of claimed sick leave in 1993. Thereafter there was a lower, but steady increase in days of future work absence, to 611 days among persons with 8-14 days of sick leave claimed in 1993. There was an interaction between sick leave and gender, education and origin respectively regarding later work absence. CONCLUSION: Periods of sick leave claimed were associated with subsequent work absence. Immigrants, women and persons with low education had the most risk of future work absence after a period of sick leave.

Sickness absence at a young age and later sickness absence, disability pension, death, unemployment and income in native Swedes and immigrants.

BACKGROUND: Sickness absence with cash benefits from the sickness insurance gives an opportunity to be relieved from work without losing financial security. There are, however, downsides to taking sickness absence. Periods of sickness absence, even short ones, can increase the risk for future spells of sickness absence and unemployment. The sickness period may in itself have a detrimental effect on health. The aim of the study was to investigate if there is an association between exposure to sickness absence at a young age and later sickness absence, disability pension, death, unemployment and income from work. METHODS: Our cohort consisted of all immigrants aged 21-25 years in Sweden in 1993 (N = 38 207) and a control group of native Swedes in the same age group (N = 225 977). We measured exposure to sickness absence in 1993 with a follow-up period of 15 years. We conducted separate analyses for men and women, and for immigrants and native Swedes. RESULTS: Exposure to ≥60 days of sickness absence in 1993 increased the risk of sickness absence [hazard ratio (HR) 1.6-11.4], unemployment (HR 1.1-1.2), disability pension (HR 1.2-5.3) and death (HR 1.2-3.5). The income from work, during the follow-up period, among individuals with spells of sick leave for ≥60 days in 1993 was around two-thirds of that of the working population who did not take sick leave. CONCLUSIONS: Individuals on sickness absence had an increased risk for work absence, death and lower future income.

Unemployment at a young age and later sickness absence, disability pension and death in native Swedes and immigrants.

BACKGROUND: Youth unemployment is an increasing problem for societies around the world. Research has revealed negative health effects of unemployment, and this longitudinal register-based cohort study examined the relationship between unemployment and later sickness absence, disability pension and death among youth in Sweden. METHOD: The study group of 199,623 individuals comprised all immigrants born between 1968 and 1972 who immigrated before 1990 (25,607) and a random sample of native Swedes in the same age-range (174,016). The baseline year was 1992, and the follow-up period was from 1993 to 2007. Subjects with unemployment benefit in 1990-91, disability pension in 1990-92, severe disorders leading to hospitalization in 1990-92 and subjects who emigrated during follow-up were excluded. RESULTS: Those who were unemployed in 1992 had elevated risk of ≥60 days of sickness absence (OR 1.02-1.49), disability pension (HR 1.08-1.62) and all except native Swedish women had elevated risk of death (HR 1.01-1.65) during follow-up compared with non-unemployed individuals. The risk of future sickness absence increased with the length of unemployment in 1992 (OR 1.06-1.54), and the risk of sickness absence increased over time. A larger part of the immigrant cohort was unemployed at baseline than native Swedes. Selection to unemployment by less healthy subjects may explain part of the association between unemployment and the studied outcomes. CONCLUSION: Unemployment at an early age may influence the future health of the individual. To a society it may lead to increased burdens on the welfare system and productivity loss for many years.

Human papillomavirus DNA and E6/E7 mRNA testing as triage in liquid-based cytology samples from primary screening.

We estimated the frequency of detection of different human papillomavirus (HPV) types in women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytology in a population-based primary screening programme. 247 liquid-based cytology (LBC) samples with ASCUS/LSIL results were tested using the LINEAR ARRAY HPV Genotyping Test (LA; Roche Diagnostics), which detects 37 HPV types. 79.4% of samples were positive by LA, and 60.7% were positive for high-risk HPV types (ASCUS: 41.2%; LSIL: 71.0%). 34 of the 37 HPV types included in LA were detected in our samples. HPV16 was detected in 18.6% of samples, and 66.8% of samples contained more than one HPV type, with a maximum of nine types observed in one LSIL sample. A random subset of 47 samples from the 247 samples tested by LA, was also analysed using the AMPLICOR HPV Test (Amplicor, Roche Diagnostics). A separate set of 42 samples, which were positive by LA for the five high-risk HPV types included in the PreTect HPV-Proofer (Proofer, NorChip AS), was also analysed for E6/E7 mRNA expression using Proofer. Concordance between LA and Amplicor was 91.5% (kappa=0.83). One false-negative and three false-positives were recorded for Amplicor, using LA as the "gold standard". Concordance between LA and Proofer was 88.0%; 100% of Proofer samples that were HPV18- positive by LA, and 75.0% of HPV16-positive samples, expressed E6/E7 mRNA. In the present study using LBC samples in a triage situation, where negative predictive value is paramount, LA gave the most reliable results.

Liquid-based cytology with HPV triage of low-grade cytological abnormalities versus conventional cytology in cervical cancer screening.

OBJECTIVE: Liquid-based cytology with supplementary human papillomavirus triage (LBC+HPV triage) of low-grade cytological abnormalities may improve the detection of cervical intraepithelial neoplasia (CIN) compared with conventional cytology. To investigate this subject, LBC+HPV triage and conventional cytology were alternated in a population-based screening setting. Cases with abnormal cytology were referred for colposcopy. METHODS: We compared the performance of LBC+HPV triage [n=4059] and conventional cytology [n=4261] in detecting CIN2 or worse [CIN2+] and CIN3 or worse [CIN3+]. We used logistic regression to assess CIN detection rates and abnormal cytology rates, which yielded unadjusted odds ratios (OR) and corresponding 95% confidence intervals (CI). We computed adjusted ORs from a multivariate logistic regression model that included potential confounders such as age, screening centre and time period. RESULTS: We found similar detection rates of CIN2+ by LBC+HPV triage and conventional cytology; the adjusted OR for the comparison of CIN detection rates was 0.87 (95% CI: 0.60-1.26) for CIN2+ and 1.00 (95% CI: 0.64-1.58) for CIN3+. We also found similar positive predictive values between methods. Thus, there was no advantage in using LBC+HPV triage as compared to conventional cytology in terms of sensitivity, specificity and positive and negative predictive value to detect histologically confirmed CIN2+ and CIN3+. CONCLUSIONS: LBC+HPV triage may lead to a reduction in unnecessary work-ups for women with abnormal cytological lesions who are negative for high-risk HPV. It is important to continuously monitor abnormal cytology rates, both when testing a new method, and after the new method has become routine.

Work and health among immigrants and native Swedes 1990-2008: a register-based study on hospitalization for common potentially work-related disorders, disability pension and mortality.

BACKGROUND: There are many immigrants in the Swedish workforce, but knowledge of their general and work-related health is limited. The aim of this register-based study was to explore whether documented migrant residents in Sweden have a different health status regarding receipt of a disability pension, mortality and hospitalization for lung, heart, psychiatric, and musculoskeletal disorders compared with the native population, and if there were variations in relation to sex, geographical origin, position on the labor market, and time since first immigration. METHODS: This study included migrants to Sweden since 1960 who were 28-47 years old in 1990, and included 243 860 individuals. The comparison group comprised a random sample of 859 653 native Swedes. These cohorts were followed from 1991 to 2008 in national registers. The immigrants were divided into four groups based on geographic origin. Hazard ratios for men and women from different geographic origins and with different employment status were analyzed separately for the six outcomes, with adjustment for age, education level, and income. The influence of length of residence in Sweden was analyzed separately. RESULTS: Nordic immigrants had increased risks for all investigated outcomes while most other groups had equal or lower risks for those outcomes than the Swedes. The lowest HRs were found in the EU 15+ group (from western Europe, North America, Australia and New Zealand). All groups, except Nordic immigrants, had lower risk of mortality, but all had higher risk of disability pension receipt compared with native Swedes. Unemployed non-Nordic men displayed equal or lower HRs for most outcomes, except disability pension receipt, compared with unemployed Swedish men. A longer time since first immigration improved the health status of men, while women showed opposite results. CONCLUSIONS: Employment status and length of residence are important factors for health. The contradictory results of low mortality and high disability pension risks need more attention. There is great potential to increase the knowledge in this field in Sweden, because of the high quality registers.

High-risk human papillomavirus E6/E7 mRNA and L1 DNA as markers of residual/recurrent cervical intraepithelial neoplasia.

The aim of this study was to assess the use of human papillomavirus (HPV) E6/E7 mRNA testing in the follow-up of women treated for cervical intraepithelial neoplasia (CIN) by conization and to compare the prognostic value of HPV E6/E7 mRNA to HPV L1 DNA and cytology. One hundred and forty-three women underwent cytological/histological testing, HPV DNA genotyping by Linear Array, and HPV E6/E7 mRNA testing by APTIMA HPV assay during follow-up after surgical treatment for histologically verified CIN. High-grade residual/recurrent disease (CIN2+/HSIL+) was identified in 7 (4.9%) women, and low-grade disease (CIN1/LSIL) in 25 (17.5%). At the inclusion visit 33 (23%) women were HPV DNA-positive; 13 (9.0%) were HPV E6/E7 mRNA-positive. HPV E6/E7 mRNA did not identify three women with high-grade disease. Presence of high-risk HPV DNA at the inclusion visit predicted 100% (95% CI 64.6-100) of high-grade residual/recurrent disease, with a specificity of 80.9% (95% CI 73.5-86.6); cytology had a sensitivity of 85.7%, and a specificity of 87.5%. HPV E6/E7 mRNA testing was a poor predictor of treatment failure, with a sensitivity of 57.1% (95% CI 25.0-84.2), but high specificity (93.4%; 95% CI 87.9-96.5). Detection of high-risk HPV DNA after treatment by conization identified 100% of women with residual/recurrent high-grade disease, whereas HPV E6/E7 mRNA testing was a poor predictor of treatment failure. This study suggests that a negative HPV mRNA result cannot exclude the risk of malignant progression, and that HPV E6/E7 mRNA testing by APTIMA HPV assay is not useful in the follow-up of women treated for CIN.

Evidence for thalamic involvement in the thermal grill illusion: an FMRI study.

BACKGROUND: Perceptual illusions play an important role in untangling neural mechanisms underlying conscious phenomena. The thermal grill illusion (TGI) has been suggested as a promising model for exploring percepts involved in neuropathic pain, such as cold-allodynia (pain arising from contact with innocuous cold). The TGI is an unpleasant/painful sensation from touching juxtapositioned bars of cold and warm innocuous temperatures. AIM: To develop an MRI-compatible TGI-unit and explore the supraspinal correlates of the illusion, using fMRI, in a group of healthy volunteers. METHODS: We constructed a TGI-thermode allowing the rapid presentation of warm(41°C), cold(18°C) and interleaved(41°C+18°C = TGI) temperatures in an fMRI-environment. Twenty volunteers were tested. The affective-motivational ("unpleasantness") and sensory-disciminatory ("pain-intensity") dimensions of each respective stimulus were rated. Functional images were analyzed at a corrected α-level <0.05. RESULTS: The TGI was rated as significantly more unpleasant and painful than stimulation with each of its constituent temperatures. Also, the TGI was rated as significantly more unpleasant than painful. Thermal stimulation versus neutral baseline revealed bilateral activations of the anterior insulae and fronto-parietal regions. Unlike its constituent temperatures the TGI displayed a strong activation of the right (contralateral) thalamus. Exploratory contrasts at a slightly more liberal threshold-level also revealed a TGI-activation of the right mid/anterior insula, correlating with ratings of unpleasantness (rho = 0.31). CONCLUSION/SIGNIFICANCE: To the best of our knowledge, this is the first fMRI-study of the TGI. The activation of the anterior insula is consistent with this region's putative role in processing of homeostatically relevant feeling-states. Our results constitute the first neurophysiologic evidence of thalamic involvement in the TGI. Similar thalamic activity has previously been observed during evoked cold-allodynia in patients with central neuropathic pain. Our results further the understanding of the supraspinal correlates of the TGI-phenomenon and pave the way for future inquiries into if and how it may relate to neuropathic pain.

The influence of brushing force and stroking velocity on dynamic mechanical allodynia in patients with peripheral neuropathy.

Recently we demonstrated brush-evoked allodynia to be a partially graded phenomenon since increased brushing length and number of strokes significantly increased the brush-evoked pain intensity. In this study the influence of stroking velocity and brushing force on dynamic mechanical allodynia was examined in 16 patients with peripheral neuropathy. Brush-evoked allodynia was induced by lightly stroking 60mm of the skin twice with a 16 mm wide brush while varying stroking velocity (10, 20, 30 mm/s) and brushing force (10, 20, 40 g). Intensity and duration of brush-evoked allodynia was recorded using a computerized visual analogue scale. The total brush-evoked pain intensity, including painful aftersensation was calculated as the area under the curve. Significantly increased total brush-evoked pain intensity was demonstrated with lower stroking velocity (P<0.001) and higher brushing force (P<0.05). Higher maximum pain intensity was reported with higher brushing force. In conclusion, our findings demonstrated a significant relationship between the total brush-evoked pain intensity and stroking velocity as well as brushing force. Together with previously accumulated data these results substantiate the usefulness of this semi-quantitative assessment method in longitudinal studies on dynamic mechanical allodynia.

Work environment and production development in Swedish manufacturing industry.

Swedish manufacturing industry has previous held a leading position regarding the development of attractive industrial work environments, but increasing market competition has changed the possibilities to maintain the position. The purpose of this literature study is therefore to describe and analyze how Swedish manufacturing industry manages work environment and production development in the new millennium. The description and analysis is based on recently reported Swedish research and development. The gathered picture of how production systems generally are developed in Sweden strongly contrasts against the idealized theoretical and legal view of how production systems should be developed. Even if some of the researchers' and authorities' ambitions and demands may seem unrealistically high today, there still is a very large potential for improving the processes and tools for designing production systems and work environment.

E6/E7 mRNA expression analysis: a test for the objective assessment of cervical adenocarcinoma in clinical prognostic procedure.

Detection of E6/E7 mRNA expression using the real-time nucleic acid sequence-based amplification assay (NASBA) PreTect HPV-Proofer was compared with results of human papillomavirus (HPV) DNA detection in 98 paraffin-embedded samples from patients with cervical adenocarcinoma. HR-HPV DNA was detected in 61 (62%), while HR-HPV E6/E7 mRNA was detected in 63 (64%) of the samples. Correlation between results from DNA analyses and the E6/E7 mRNA assay showed consistent results in 87% of samples (47 of 54). The results from these two methods in detecting presence of HPV infection of any type agreed in 77%. Overall agreement between the methods was seen in 82 of the 98 cases (84%). When evaluating change in sensitivity for detection of HPV positives by adding more HPV types to the HPV DNA assay, maximum sensitivity was reached by targeting four HPV types. The coverage of HPV DNA presence was 76.9%, while the E6/E7 mRNA assay achieved a maximum coverage of 80.8% using only three HPV types. Thus, E6/E7 oncogene expression analysis may provide a more objective test for assessment of neoplastic glandular cells. Further studies may reveal whether the clinical performance of the E6/E7 mRNA assay will be of prognostic value in management of cervical adenocarcinoma.

Piece rates and their effects on health and safety - a literature review.

The purpose of this study was to carry out a broad survey and analysis of relevant research articles about piece rate wages and their effects on health and safety that were published internationally until the fall of 2008. The aim was to summarize and describe the state of the art of the research in this field and if possible draw conclusions from the accumulated research results. A total of 75 research articles were examined extensively and 31 of these were found relevant and had sufficient quality to serve the purpose of this study. The findings of these relevant articles are summarized and analyzed in the survey. Since the late 1980s, there has been a change of research focus regarding piece rates and their effects on health and safety. More recent research shows a clear interest for health, musculoskeletal injuries, physical workload, pains and occupational injuries. The previous interest in risk behavior, security and accidents is still there, but no longer dominates the research scene. Although research is still sparse and fragmented, much of the accumulated knowledge about the effects of piece rate work tells us that piece rates in many situations have a negative effect on health and safety. The fact that 27 of the 31 studied articles found negative effects of piece rates on different aspects of health and safety does not prove causality, but together they give very strong support for the hypothesis that in most situations piece rates have negative effects on health and safety. In order to achieve better knowledge about the effects of piece rates in branches where piece rates are regarded problematic, further research is needed and such research has to be designed to meet the specific questions that are to be answered.

Detection of genomic amplification of the human telomerase gene TERC, a potential marker for triage of women with HPV-positive, abnormal Pap smears.

The vast majority of invasive cervical carcinomas harbor additional copies of the chromosome arm 3q, resulting in genomic amplification of the human telomerase gene TERC. Here, we evaluated TERC amplification in routinely collected liquid based cytology (LBC) samples with histologically confirmed diagnoses. A set of 78 LBC samples from a Swedish patient cohort were analyzed with a four-color fluorescence in situ hybridization probe panel that included TERC. Clinical follow-up included additional histological evaluation and Pap smears. Human papillomavirus status was available for all cases. The correlation of cytology, TERC amplification, human papillomavirus typing, and histological diagnosis showed that infection with high-risk human papillomavirus was detected in 64% of the LBC samples with normal histopathology, in 65% of the cervical intraepithelial neoplasia (CIN)1, 95% of the CIN2, 96% of the CIN3 lesions, and all carcinomas. Seven percent of the lesions with normal histopathology were positive for TERC amplification, 24% of the CIN1, 64% of the CIN2, 91% of the CIN3 lesions, and 100% of invasive carcinomas. This demonstrates that detection of genomic amplification of TERC in LBC samples can identify patients with histopathologically confirmed CIN3 or cancer. Indeed, the proportion of TERC-positive cases increases with the severity of dysplasia. Among the markers tested, detection of TERC amplification in cytological samples has the highest combined sensitivity and specificity for discernment of low-grade from high-grade dysplasia and cancer.

Laser capture microdissection of cervical human papillomavirus infections: copy number of the virus in cancerous and normal tissue and heterogeneous DNA methylation.

Research on the pathogenicity of human papillomaviruses (HPVs) during cervical carcinogenesis often relies on the study of homogenized tissue or cultured cells. This approach does not detect molecular heterogeneities within the infected tissue. It is desirable to understand molecular properties in specific histological contexts. We asked whether laser capture microdissection (LCM) of archival cervical tumors in combination with real-time polymerase chain reaction and bisulfite sequencing permits (i) sensitive DNA diagnosis of small clusters of formalin-fixed cells, (ii) quantification of HPV DNA in neoplastic and normal cells, and (iii) analysis of HPV DNA methylation, a marker of tumor progression. We analyzed 26 tumors containing HPV-16 or 18. We prepared DNA from LCM dissected thin sections of 100 to 2000 cells, and analyzed aliquots corresponding to between nine and 70 cells. We detected nine to 630 HPV-16 genome copies and one to 111 HPV-18 genome copies per tumor cell, respectively. In 17 of the 26 samples, HPV DNA existed in histologically normal cells distant from the margins of the tumors, but at much lower concentrations than in the tumor, suggesting that HPVs can infect at low levels without pathogenic changes. Methylation of HPV DNA, a biomarker of integration of the virus into cellular DNA, could be measured only in few samples due to limited sensitivity, and indicated heterogeneous methylation patterns in small clusters of cancerous and normal cells. LCM is powerful to study molecular parameters of cervical HPV infections like copy number, latency and epigenetics.

Follow-up after treatment of cervical intraepithelial neoplasia by human papillomavirus genotyping.

OBJECTIVE: To assess the use of human papillomavirus genotyping in cervical intraepithelial neoplasia posttreatment follow-up. STUDY DESIGN: Prospective observational study. Ninety women underwent cytologic testing and human papillomavirus genotyping at the follow-up visit after conization. Cones were retrospectively genotyped. A second cytologic follow-up was performed. RESULTS: Margin status and presence of cervical intraepithelial neoplasia 3+ in the cone were poor predictors of treatment outcome (sensitivity, < 50%; diagnostic odds ratio,

Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA testing in primary cervical cancer screening.

BACKGROUND: Primary cervical screening with both human papillomavirus (HPV) DNA testing and cytological examination of cervical cells with a Pap test (cytology) has been evaluated in randomized clinical trials. Because the vast majority of women with positive cytology are also HPV DNA positive, screening strategies that use HPV DNA testing as the primary screening test may be more effective. METHODS: We used the database from the intervention arm (n = 6,257 women) of a population-based randomized trial of double screening with cytology and HPV DNA testing to evaluate the efficacy of 11 possible cervical screening strategies that are based on HPV DNA testing alone, cytology alone, and HPV DNA testing combined with cytology among women aged 32-38 years. The main outcome measures were sensitivity for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) within 6 months of enrollment or at colposcopy for women with a persistent type-specific HPV infection and the number of screening tests and positive predictive value (PPV) for each screening strategy. All statistical tests were two-sided. RESULTS: Compared with screening by cytology alone, double testing with cytology and for type-specific HPV persistence resulted in a 35% (95% confidence interval [CI] = 15% to 60%) increase in sensitivity to detect CIN3+, without a statistically significant reduction in the PPV (relative PPV = 0.76, 95% CI = 0.52 to 1.10), but with more than twice as many screening tests needed. Several strategies that incorporated screening for high-risk HPV subtypes were explored, but they resulted in reduced PPV compared with cytology. Compared with cytology, primary screening with HPV DNA testing followed by cytological triage and repeat HPV DNA testing of HPV DNA-positive women with normal cytology increased the CIN3+ sensitivity by 30% (95% CI = 9% to 54%), maintained a high PPV (relative PPV = 0.87, 95% CI = 0.60 to 1.26), and resulted in a mere 12% increase in the number of screening tests (from 6,257 to 7,019 tests). CONCLUSIONS: Primary HPV DNA-based screening with cytology triage and repeat HPV DNA testing of cytology-negative women appears to be the most feasible cervical screening strategy.