RESUMO
An increase in cervical cancer incidence in Sweden from 2014 to 2015 has been attributed to an increase in false-negative cytological findings before cancer diagnoses. Years later, we performed a long-term follow-up to investigate whether the problem persisted. At each calendar year from 2016 to 2020, we identified women with prior normal cervical screening results through linkage to the Swedish National Cervical Screening Registry. We reported their incidence rates (IRs) of invasive cervical cancer in consecutive years and compared the IRs over time. For the years 2016 to 2020, there was no overall change in cervical cancer incidence after two normal cytology in the last two screening intervals. However, there was a further 62% increase among women 50 to 60 years of age with normal cytology in the past two screening intervals. The incidence rate of cervical cancer was high among nonscreened women and low among HPV-screened women with negative results, with no trends over time. Our results imply that the previously reported decrease in sensitivity of cervical cytology is persisting. Although primary cytology screening is no longer used, cytology is used in triaging among HPV-positive women. Our findings suggest that improved triaging is needed, for example, improved quality assurance and/or use of alternative triage tests.
Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Gravidez , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Incidência , Displasia do Colo do Útero/diagnóstico , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/diagnóstico , Seguimentos , Detecção Precoce de Câncer , Programas de Rastreamento/métodos , Colposcopia , Esfregaço VaginalRESUMO
The elimination of cervical cancer rests on high efficacy of human papillomavirus (HPV) vaccines. The HPV type distribution among cases of invasive cervical cancer (ICC) is used to make predictions about the impact of eliminating different types of HPV, but accumulating evidence of differences in age-specific cancer incidence by HPV type exists. We used one of the largest population-based series of HPV genotyping of ICCs (n = 2,850; Sweden, 2002-2011) to estimate age-specific ICC incidence by HPV type and obtain estimates of the cancer-protective impact of the removal of different HPV types. In the base case, the age-specific ICC incidence had 2 peaks, and the standardized lifetime risk (SLTR, the lifetime number of cases per birth cohort of 100,000 females) for HPV-positive ICC was 651 per 100,000 female births. In the absence of vaccine types HPV 16 and HPV 18, the SLTR for ICC was reduced to 157 per 100,000 female births (24% of HPV-positive SLTR). Elimination of all 9 types that can currently be vaccinated against reduced the remaining SLTR to 47 per 100,000 female births (7%), the remaining ICC incidence only slowly increasing with age. In conclusion, after elimination of vaccine-protected HPV types, very few cases of ICC will be left, especially among fertile, reproductive-age women.
Assuntos
Papillomaviridae/imunologia , Sistema de Registros , Neoplasias do Colo do Útero/epidemiologia , Vacinação/métodos , Adulto , Fatores Etários , Feminino , Seguimentos , Humanos , Incidência , Infecções por Papillomavirus , Estudos Retrospectivos , Suécia/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologiaRESUMO
Our study used a refined case-control cervical cancer Audit framework to investigate effectiveness of cervical screening, with measures of three screening failures: irregular-participation, cervical cancer developed after cytological abnormalities and after normal screening results. The register-based study included 4,254 cervical cancer cases diagnosed in Sweden during 2002-2011, and 30 population-based controls per case. We used conditional logistic regression models to examine relative risks of cervical cancer in relation to screening participation and screening results in the past two screening rounds from 6 months before cancer diagnosis. We found that women unscreened in past two screening rounds showed four times increased risk of cervical cancer compared to women screened in time (OR = 4.1, 95% CI = 3.8-4.5), and women unscreened in the previous round but screened in the most recent round also showed a statistically significantly elevated risk (OR = 1.6, 95% CI = 1.5-1.8). Women having abnormality in previous two rounds exhibited higher risk of cervical cancer compared to women screened with normal results, while having normal results in the subsequent round after the abnormality also yielded an increased risk (OR = 4.0, 95% CI = 3.2-5.1). Being screened with only normal results was associated with 89% risk reduction for squamous cell cancer, compared to women unscreened, but only 60% reduction for adenocarcinoma. Our findings emphasize the importance of routine participation in cervical screening and suggest that management of abnormalities, as well as sensitivity of the test, warrants improvement especially for preventing cervical adenocarcinoma. The Audit framework serves as routine evaluation model and the findings benchmark for future evaluation of changes in screening practice.
Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Programas de Rastreamento/organização & administração , Auditoria Médica/estatística & dados numéricos , Participação do Paciente/estatística & dados numéricos , Neoplasias do Colo do Útero/epidemiologia , Adulto , Idoso , Benchmarking/estatística & dados numéricos , Estudos de Casos e Controles , Colo do Útero/patologia , Feminino , Humanos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Teste de Papanicolaou/estatística & dados numéricos , Gravidez , Avaliação de Programas e Projetos de Saúde , Sistema de Registros/estatística & dados numéricos , Medição de Risco , Suécia/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Adulto JovemRESUMO
Background: Cervical cancer incidence in Sweden decreased from 24/100,000 in 1965 to 8/100,000 in 2011, but has from 2014 increased to 11/100,000. The increase appears to correlate to screening history. We perform a study of the cancer risk change in relation to screening history over two screening rounds to verify the correlation.Material and methods: We studied the cohorts of all 3,047,850 individual women living in Sweden in each year from 2002-2015. Registry linkages between the Total Population Register, the Swedish National Cervical Screening Registry, the Swedish Cervical Cancer Audit database and the National Quality Register for Gynecological Cancer, defined the incidence rates of invasive cervical cancer comparing time periods 2002-2013 to 2014-2015, in women whose screening history in 2 screening intervals prior to each year were either (i) adequately screened with normal results (almost exclusively cytology, 52% of the population) or (ii) unscreened (13% of the population). We also investigated the incidence increase by time since a normal smear performed in 2002-2012.Results: Among women adequately screened with normal results there was a strong incidence increase in 2014-2015 compared to previous years (Incidence rate ratio (IRR) = 1.59, 95%CI = 1.36-1.85), but no significant increase among unscreened women (IRR = 1.09, 95%CI = 0.94-1.27). There was no increase in incidence 0-2.5 years after a normal smear over the study period (IRR = 1.04, 95% CI = 0.88-1.24), but a strong increase 3-4 years after a normal smear since year 2009 (IRR = 1.52, 95% CI = 1.25-1.84).Conclusion: The results suggest that the overall increase is associated with an increased cancer risk in women adequately screened with normal cytological results. Possibly, precursor lesions missed in one screening round might result in detection of early stage invasive cancer in the subsequent screening.
Assuntos
Programas de Rastreamento/estatística & dados numéricos , Neoplasias do Colo do Útero/epidemiologia , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Suécia/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/estatística & dados numéricosRESUMO
BACKGROUND: High-risk human papillomavirus (hrHPV) infection is established as the major cause of invasive cervical cancer (ICC). However, whether hrHPV status in the tumor is associated with subsequent prognosis of ICC is controversial. We aim to evaluate the association between tumor hrHPV status and ICC prognosis using national registers and comprehensive human papillomavirus (HPV) genotyping. METHODS AND FINDINGS: In this nationwide population-based cohort study, we identified all ICC diagnosed in Sweden during the years 2002-2011 (4,254 confirmed cases), requested all archival formalin-fixed paraffin-embedded blocks, and performed HPV genotyping. Twenty out of 25 pathology biobanks agreed to the study, yielding a total of 2,845 confirmed cases with valid HPV results. Cases were prospectively followed up from date of cancer diagnosis to 31 December 2015, migration from Sweden, or death, whichever occurred first. The main exposure was tumor hrHPV status classified as hrHPV-positive and hrHPV-negative. The primary outcome was all-cause mortality by 31 December 2015. Five-year relative survival ratios (RSRs) were calculated, and excess hazard ratios (EHRs) with 95% confidence intervals (CIs) were estimated using Poisson regression, adjusting for education, time since cancer diagnosis, and clinical factors including age at cancer diagnosis and International Federation of Gynecology and Obstetrics (FIGO) stage. Of the 2,845 included cases, hrHPV was detected in 2,293 (80.6%), and we observed 1,131 (39.8%) deaths during an average of 6.2 years follow-up. The majority of ICC cases were diagnosed at age 30-59 years (57.5%) and classified as stage IB (40.7%). hrHPV positivity was significantly associated with screen-detected tumors, young age, high education level, and early stage at diagnosis (p < 0.001). The 5-year RSR compared to the general female population was 0.74 (95% CI 0.72-0.76) for hrHPV-positive cases and 0.54 (95% CI 0.50-0.59) for hrHPV-negative cases, yielding a crude EHR of 0.45 (95% CI 0.38-0.52) and an adjusted EHR of 0.61 (95% CI 0.52-0.71). Risk of all-cause mortality as measured by EHR was consistently and statistically significantly lower for cases with hrHPV-positive tumors for each age group above 29 years and each FIGO stage above IA. The difference in prognosis by hrHPV status was highly robust, regardless of the clinical, histological, and educational characteristics of the cases. The main limitation was that, except for education, we were not able to adjust for lifestyle factors or other unmeasured confounders. CONCLUSIONS: In this study, women with hrHPV-positive cervical tumors had a substantially better prognosis than women with hrHPV-negative tumors. hrHPV appears to be a biomarker for better prognosis in cervical cancer independent of age, FIGO stage, and histological type, extending information from already established prognostic factors. The underlying biological mechanisms relating lack of detectable tumor hrHPV to considerably worse prognosis are not known and should be further investigated.
Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/virologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/virologia , Papillomaviridae/genética , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/virologia , Adenocarcinoma/patologia , Adulto , Idoso , Medicamentos Biossimilares , Carcinoma de Células Escamosas/patologia , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Papillomaviridae/isolamento & purificação , Prognóstico , Estudos Prospectivos , Sistema de Registros , Taxa de Sobrevida , Suécia/epidemiologia , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: The Swedish National Cervical Screening Registry collects and evaluates comprehensive, nationwide health data to optimise organised cervical cancer prevention. Since all cervical cancer specimens are saved in biobanks, population-based data from the specimens should be available for analysis and linkage with other health information. METHODS: We identified all cervical cancers diagnosed in Sweden during 2002-2011 (4254 confirmed cases) and requested the tissue blocks to retrieve human papillomavirus (HPV) genotype data using general primer PCR with Luminex genotyping and real-time PCR targeting the E6/E7 regions of HPV16/18. RESULTS: We obtained blocks from 2932/4254 (69%) of cases. Valid HPV genotyping data was retrieved for 2850 cases (97%). The most common type was HPV16 (60%), followed by HPV18 (19%), HPV45 (7%), HPV31 (3%), HPV33 (2%), HPV52 (2%), HPV39 (1%), HPV70 (1%), HPV56 (1%), HPV35 (1%), HPV58 (1%) and HPV59 (1%). Ninety-six percent of all HPV-positive cases had a single infection. Eighty-nine cases were HPV-positive only when testing for the HPV16/18-E6/E7 region. CONCLUSIONS: We present one of the largest series of HPV-genotyped cervical cancers to date. The systematic collection of cervical cancer HPV genotyping data by the screening registry will facilitate prevention and monitoring of HPV type-specific disease burden.
Assuntos
Detecção Precoce de Câncer , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologia , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Genótipo , Humanos , Proteínas Oncogênicas Virais/genética , Papillomaviridae/classificação , Papillomaviridae/patogenicidade , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/classificação , Infecções por Papillomavirus/genética , Proteínas Repressoras/genética , Suécia/epidemiologia , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/genéticaRESUMO
BACKGROUND: The relatively high incidence of cervical cancer in women at older ages is a continuing concern in countries with long-established cervical screening. Controversy remains on when and how to cease screening. Existing population-based studies on the effectiveness of cervical screening at older ages have not considered women's screening history. We performed a nationwide cohort study to investigate the incidence of cervical cancer after age 60 years and its association with cervical screening at age 61-65, stratified by screening history at age 51-60. METHODS AND FINDINGS: Using the Total Population Register, we identified 569,132 women born between 1 January 1919 and 31 December 1945, resident in Sweden since age 51. Women's cytological screening records, cervical cancer occurrence, and FIGO stage (for those diagnosed with cancer) were retrieved from national registers and medical charts. We calculated the cumulative incidence of cervical cancer from age 61 to age 80 using a survival function considering competing risk, and estimated the hazard ratio (HR) of cervical cancer in relation to screening status at age 61-65 from Cox models, adjusted for birth cohort and level of education, conditioning on women's screening history in their 50s. In women unscreened in their 50s, the cumulative incidence up to age 80 was 5.0 per 1,000 women, and screening at age 61-65 was associated with a lower risk for cervical cancer (HR = 0.42, 95% CI 0.24-0.72), corresponding to a decrease of 3.3 cancer cases per 1,000 women. A higher cumulative incidence and similarly statistically significant risk decrease was seen for women with abnormal smears in their 50s. In women adequately or inadequately screened with only normal results between age 51 and age 60, the cumulative incidence of cervical cancer from age 61 to 80 was 1.6 and 2.5 per 1,000 women, respectively, and further screening at age 61-65 was not associated with statistically significant decreases of cervical cancer risk up to age 80, but with fewer cancer cases of advanced stages at age 61-65. Adjustment for potential lifestyle confounders was limited. CONCLUSIONS: In this study, cervical screening with cytology at age 61-65 was associated with a statistically significant reduction of subsequent cervical cancer risk for women who were unscreened, or screened with abnormalities, in their 50s. In women screened with normal results in their 50s, the risk for future cancer was not sizeable, and the risk reduction associated with continued screening appeared limited. These findings should inform the current debate regarding age and criteria to discontinue cervical screening.
Assuntos
Adenocarcinoma/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Fatores Etários , Idoso , Células Escamosas Atípicas do Colo do Útero/patologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Detecção Precoce de Câncer , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Teste de Papanicolaou , Modelos de Riscos Proporcionais , Lesões Intraepiteliais Escamosas Cervicais/epidemiologia , Lesões Intraepiteliais Escamosas Cervicais/patologia , Suécia/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Esfregaço VaginalRESUMO
BACKGROUND: Atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion in abnormal cervical cytology among young women in cervical cancer screening is an increasing health burden, and comparative effectiveness studies of different management options for such diagnoses are needed. OBJECTIVE: The objective of the study was to compare the incidence of invasive cervical cancer, following different management options pursued after an atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion index smear. STUDY DESIGN: In this nationwide cohort study, we included all women aged 22-50 years and resident in Sweden 1989-2011 and with at least 1 cervical smear registered during the study period (n = 2,466,671). Follow-up of a first atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion cytological diagnosis within 25 months was classified as repeat cytology, colposcopy/biopsy, or without further assessment. Incidence rate ratios and 95% confidence intervals of subsequent cervical cancer within 6.5 years following atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion were estimated using Poisson regression by age group and management strategy. RESULTS: Women managed with repeat cytology within 6 months after atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cytology had a similar risk of cervical cancer compared with colposcopy/biopsy (incidence rate ratio, 1.1, 95% confidence interval, 0.5-2.5, and incidence rate ratio, 2.0, 95% confidence interval, 0.6-6.5, respectively) among women aged 22-27 years. For women aged 28 years and older, women managed with repeat cytology had a higher risk for cervical cancer than women managed with colposcopy/biopsy. CONCLUSION: Our findings suggest that women with a first cytological diagnosis of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion up to age 27 years may indeed be safely followed up with repeat cytology within 6 months. A large amount of colposcopies that are currently performed in this group, therefore, could safely be discontinued.
Assuntos
Adenocarcinoma/epidemiologia , Assistência ao Convalescente/métodos , Células Escamosas Atípicas do Colo do Útero/patologia , Carcinoma Adenoescamoso/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Colposcopia/estatística & dados numéricos , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Biópsia , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Teste de Papanicolaou , Distribuição de Poisson , Análise de Regressão , Lesões Intraepiteliais Escamosas Cervicais/terapia , Suécia/epidemiologia , Esfregaço Vaginal , Adulto JovemRESUMO
PURPOSE: Detection of human papillomavirus (HPV) by polymerase chain reaction in invasive cervical cancer is strongly associated with prognosis but previous studies have not considered sequencing efforts. We aimed to assess the association when also including comprehensive analysis of HPV infection by deep sequencing and a longer follow-up period. MATERIALS AND METHODS: We subjected all 392 of 2,845 invasive cervical cancer cases that were polymerase chain reaction-negative for HPV to RNA sequencing on the NovaSeq 6000 platform (Illumina) and identified an additional 169 cases as HPV-positive. We followed all women from date of diagnosis to December 31, 2016, emigration, or death, whichever occurred first. The main outcome was all-cause mortality by December 31, 2016. We calculated 5-year cumulative relative survival ratios compared with the female general population and used Poisson regression to estimate excess hazard ratios of all-cause mortality by infection with any of the 13 most oncogenic (high-risk [hr]) HPV types in the tumor. All models were adjusted for age, time since diagnosis, stage, histology, and education level. RESULTS: The 5-year cumulative relative survival ratio was 0.45 (95% CI, 0.39 to 0.51) in the hrHPV-negative group, and 0.74 (95% CI, 0.72 to 0.75) in the hrHPV-positive group. This translated to a statistically significantly 43% lower excess mortality in the hrHPV-positive group compared with the hrHPV-negative (corresponding to an excess hazard ratio 0.57; 95% CI, 0.48 to 0.69). There was no association between HPV risk group, clade, or number of HPV infections and prognosis. CONCLUSION: hrHPV status is a strong determinant of cervical cancer prognosis over 15 years after diagnosis, above and beyond other established factors.
Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Papillomaviridae/genética , Prognóstico , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/diagnósticoRESUMO
A substantial proportion of women with cervical cancer that have participated in cervical screening have a history of an abnormal cytology result. Our objective was to assess the impact of histological investigation and treatment of women with abnormal cytology on the subsequent risk of invasive cervical cancer. All invasive cervical cancer cases in Sweden 1999-2001 and five population-based control women per case were investigated. Clinical investigations and treatment were analysed in case women (N = 143) and control women (N = 176) below 67 with abnormal cytology results 0.5-6.5 years before the cases' diagnosis. Cervical cancer risk in relation to investigation [histology or not, punch biopsy, cervical curettage or cone/large loop excision of the transformation zone (LLETZ)], and treatment (treatment or not, excisional or ablative) was estimated as odds ratios (ORs) using logistic regression. Absence of histological assessment was associated with increased cancer risk, both after low-grade [OR 2.37; 95% confidence intervals (CI): 1.27-4.43] and high-grade squamous atypia (8.26; 2.37-28.8). Among women with histology, absence of treatment was associated with increased cancer risk (3.68; 1.53-8.84), also when biopsy showed low-grade atypia or normal findings (3.57; 1.18-10.8). Ablative therapy associated with increased risk compared with excisional (3.82; 1.01-14.4), and laser conisation associated with decreased risk compared with LLETZ (0.06; 0.01-0.36). In conclusion, low-grade as well as high-grade squamous atypical cytology results may warrant histological investigation, treatment reduced cancer risk even when histology was negative or showed low-grade atypia indicating a need for improvements in the diagnosis of high-grade lesions, and laser conisation was the most effective treatment.
Assuntos
Lesões Pré-Cancerosas/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Adulto , Biópsia/métodos , Estudos de Casos e Controles , Conização , Gerenciamento Clínico , Detecção Precoce de Câncer , Feminino , Humanos , Invasividade Neoplásica , Vigilância da População , Lesões Pré-Cancerosas/terapia , Risco , Suécia/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Esfregaço VaginalRESUMO
Sweden has experienced an unexpected >30% increase in cervical cancer incidence among women with normal cytological screening results. We therefore performed a nationwide assessment of false-negative cytology before invasive cervical cancer. The Swedish national cervical screening registry identified 2,150 normal cytologies taken up to 10 years before 903 cases of invasive cervical cancer. The 27 cytological laboratories in Sweden were asked to rereview the slides, and all of them completed the rereview. One thousand nine hundred fifteen slides were retrieved and reviewed. Abnormalities were found in 30% of the slides, and the proportion of slides that had a changed diagnosis on rereview increased on average by 3.9% per sampling year during 2001-2016 (p < 0.03). We also asked for rereview of normal smears taken up to 42 months before a histopathologically diagnosed high-grade squamous intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS). 19/27 laboratories responded, and out of 6,101 normal smears taken before HSIL/AIS, 5,918 were retrieved and rereviewed. The diagnosis was changed in 25% of cases. In summary, we found an increasing time trend of false-negative smears taken before invasive cervical cancer. This indicates a decreased protection of normal cytology in the screening program supporting earlier findings that this is the main reason behind the recent Swedish increase in cervical cancer. We suggest that optimal cervical cancer control may be promoted by routine nationally coordinated rereview of negative smears before high-grade cervical lesions or invasive cervical cancer.
Assuntos
Detecção Precoce de Câncer , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adulto , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Esfregaço VaginalRESUMO
BACKGROUND: Highly increased risk of injuries has been noted around the time of cancer diagnosis. Whether there is a similar increase in risk around the diagnosis of cervical cancer and its precursor lesions was unknown. METHODS: We performed a cohort study including 3,016,307 Swedish women that participated in cervical screening during 2001 to 2012. We calculated the incidence rates (IR) of hospitalized iatrogenic or noniatrogenic injuries during the diagnostic workup, and the time interval from smear or punch biopsy until surgical treatment or 2 months after the last smear or biopsy, among women with invasive cervical cancer (ICC) or its precursor lesions. We calculated the IRs of injuries during the 2 months after a normal smear among the other women as reference. IR ratios (IRR) and 95% confidence intervals (CI) were calculated using Poisson regression. RESULTS: Compared with other women, there was an increased rate of iatrogenic injuries during the diagnostic workup of women with ICC (IR, 0.58 per 1,000 person-months; IRR, 8.55; 95% CI, 3.69-19.80) as well as of women with cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ (IR, 0.09 per 1,000 person-months; IRR, 3.04; 95% CI, 1.73-5.34). We also found an increased rate of noniatrogenic injuries during the diagnostic workup of women with invasive cancer (IR, 0.65 per 1,000 person-months; IRR, 2.48; 95% CI, 1.30-4.47). CONCLUSIONS: Although rare, there was an increased risk of inpatient care for iatrogenic and noniatrogenic injuries during the diagnostic workup of women with ICC. IMPACT: Women experienced burden of medical complications and psychologic distress around diagnosis of a potential cervical cancer.
Assuntos
Neoplasias do Colo do Útero/complicações , Ferimentos e Lesões/etiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Suécia , Ferimentos e Lesões/patologia , Adulto JovemRESUMO
OBJECTIVE: We sought to evaluate the management of women with abnormal cytology in terms of subsequent risk of invasive cervical cancer. STUDY DESIGN: The screening histories of all invasive cervical cancer cases diagnosed in Sweden 1999-2001 and of 5 population-based controls per case were reviewed. In all, 159 patients and 258 control subjects aged < 67 years had an abnormal smear result 0.5-6.5 years prior to cancer diagnosis. The cervical cancer risk was estimated in relation to management by calculating odds ratios. RESULTS: Histologic assessment of low-grade squamous abnormalities strongly reduced the risk compared to repeated cytology (odds ratio, 0.46; 95% confidence interval, 0.24-0.89). Delaying histologic assessment was also associated with a higher risk (odds ratio, 5.65; 95% confidence interval, 1.39-23.05). After high-grade squamous atypia, absence of any cytologic or histologic specimen was a major determinant of cancer risk (odds ratio, 12.52; 95% confidence interval, 1.42-infinitive). CONCLUSION: For adequate protection against invasive cervical cancer, further assessment with histology must be recommended also for women with low-grade squamous abnormalities.
Assuntos
Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Teste de Papanicolaou , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal/estatística & dados numéricos , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Sistema de Registros , Fatores de Risco , Suécia/epidemiologiaRESUMO
UNLABELLED: OBJECTIVE. Atypical squamous cells of undetermined significance (ASCUS) cells, occurring in organized cytological screening, may be either high-risk human papillomavirus (HPV) positive or negative. To refine the assessment of women with ASCUS, a high-risk HPV-DNA test is recommended as triage in Sweden. METHODS: A total of 197 consecutive women (mean age 39 years, range 21-60) with a diagnosis of ASCUS from the primary screening were selected for triage. Their cervical smears were collected and evaluated by using conventional cytological examination in combination with a high-risk HPV-DNA test (hybrid capture 2). The women were categorized into four groups: Group A, Cytology + /HPV + ; Group B, Cytology-/HPV + ; Group C, Cytology + /HPV-; and Group D, Cytology-/ HPV-. Women within Groups A-C were admitted for colposcopy and cervical biopsy. The women in Group D were considered as a low-risk group for tumor development, and were re-examined after three years in the next round of the organized screening. RESULTS: In women in Group A (n=58) the prevalence of histological verified CIN2-3 was 41%, in Group B (n=41) 20%, and in Group C (n=9) 0%. In Group D (n=89), repeated primary screening three years later revealed CIN2-3 in two biopsies from 74 women studied (<3%). The prevalence of a high-risk HPV infection decreased with age in women with ASCUS. It was 74% in women <30 years and 19% in women > or =50 years. CONCLUSIONS: Adding a high-risk HPV test in secondary screening increased the identification of women with CIN2-3 lesions by 33% in comparison with repeat cytology (p=0.01). The clinical significance of the ASCUS diagnosis varied with age of the women.
Assuntos
DNA Viral/análise , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Triagem/métodos , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Fatores Etários , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Valor Preditivo dos Testes , Fatores de Risco , Suécia , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal , Adulto Jovem , Displasia do Colo do Útero/patologiaRESUMO
Emerging evidence suggests a role of psychologic factors in the progression of different cancer types. However, it is unclear whether psychologic distress around the time of diagnosis of invasive cervical cancer places patients at a higher risk of cancer-specific mortality, independently of tumor characteristics and treatment modalities. We conducted a nationwide cohort study, including 4,245 patients with newly diagnosed cervical cancer during 2002-2011 in Sweden. Psychologic distress was indicated by a clinical diagnosis of depression, anxiety, or stress reaction and adjustment disorders, or the experience of a stressful life event, including death or severe illness of a family member, divorce, or between jobs, from one year before cancer diagnosis and onwards. We calculated the HRs of cancer-specific mortality among the patients exposed to psychologic distress, compared with unexposed patients, controlling for socioeconomic characteristics and other known prognostic indicators such as tumor and treatment characteristics. We found that patients exposed to psychologic distress had an increased risk of cancer-specific mortality (HR 1.33; 95% CI, 1.14-1.54). The association was primarily driven by distress experienced within one year before or after diagnosis (HR 1.30; 95% CI, 1.11-1.52), but not thereafter (HR 1.12; 95% CI, 0.84-1.49). In summary, our study shows that psychiatric disorders and stressful life events around cancer diagnosis are associated with increased cancer-specific mortality among patients with cervical cancer, independent of tumor characteristics and treatment modality. SIGNIFICANCE: These findings support the integration of psychologic screening and intervention in the clinical management of patients with cervical cancer, particularly around the time of cancer diagnosis.
RESUMO
OBJECTIVES: To examine the association of cervical cytology screening with the risk of adenosquamous cell carcinoma (ASC) and rare histological types of invasive cervical carcinoma (RICC), using comprehensive registry data, and to assess tumour human papillomavirus status of ASC and RICC. DESIGN: Nationwide, population based, nested case-control study. SETTING: Sweden. PARTICIPANTS: All cases of invasive cervical carcinoma in Sweden during 2002-11 (4254 confirmed cases after clinical and histopathological review). 338 cases were neither squamous cell carcinoma nor adenocarcinoma, including 164 cases of ASC and 174 cases of RICC (glassy cell carcinoma, clear cell carcinoma, small cell carcinoma, neuroendocrine cell carcinoma, large cell carcinoma, and undifferentiated carcinoma). 30 birth year matched controls from the general Swedish population were matched to each case by applying incidence density sampling. MAIN OUTCOME MEASURES: Conditional logistic regression was used to calculate odds ratios, interpreted as incidence rate ratios, for risk of ASC and RICC in relation to screening status and screening history, adjusted for education. Human papillomavirus distribution of ASC and RICC was based on available archival tumour tissues from most Swedish pathology biobanks. RESULTS: Women with two screening tests in the previous two recommended screening intervals had a lower risk of ASC (incidence rate ratio 0.22, 95% confidence interval 0.14 to 0.34) and RICC (0.34, 0.21 to 0.55), compared with women without any test. High risk human papillomavirus was detected in 148/211 (70%) cases with valid human papillomavirus results from tumour tissues. The risk reduction among women with tumours that were positive (incidence rate ratio 0.28, 0.18 to 0.46) and negative (0.27, 0.13 to 0.59) for high risk human papillomavirus was similar, compared with women who did not attend any test. CONCLUSIONS: Cervical screening is associated with reduced risk of ASC and RICC, and most ASC and RICC are positive for high risk human papillomavirus. This evidence provides a benchmark for evaluating future cervical screening strategies.
Assuntos
Carcinoma Adenoescamoso/diagnóstico , Carcinoma Adenoescamoso/epidemiologia , Detecção Precoce de Câncer , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Adulto , Idoso , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Colo do Útero/patologia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Sistema de Registros , Risco , Comportamento de Redução do Risco , Neoplasias do Colo do Útero/patologia , Adulto JovemRESUMO
Cervical cancer has increased in Sweden in recent years. The increase is 17% in 2014-15 compared to the reference period 2002-13. The increase is largest for adenocarcinoma (+ 31%) and shows remarkable differences between counties, from continued incidence decreases to increases of >80%. The increase is seen in most ages that are offered screening, but is confined to early stage cancers and there is no increase in mortality. Population test coverage of screening has increased since 2002. The Swedish National Cervical Screening Registry has analysed the increase in relation to screening history. The most significant increase (+ 30%) is seen in women who had a normal cervical smear (P < 0.0001) in the preceding screening interval. The cancer risk for women who previously had a high grade abnormality has also increased (P = 0.0009). Data from several laboratories still show very low cancer risk following normal cytology, indicating that the increase is related to factors that can be addressed. All data on re-review of samples taken before cancer and high grade intraepithelial neoplasia will be requested and nationally analyzed to further elucidate the exact cause.
Assuntos
Programas de Rastreamento , Neoplasias do Colo do Útero , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adulto , Idoso , Feminino , Humanos , Incidência , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/diagnóstico , Neoplasias de Células Escamosas/epidemiologia , Neoplasias de Células Escamosas/patologia , Sistema de Registros , Medição de Risco , Fatores de Risco , Suécia/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Esfregaço VaginalAssuntos
Neoplasias do Colo do Útero/prevenção & controle , Alphapapillomavirus/classificação , Alphapapillomavirus/genética , Alphapapillomavirus/isolamento & purificação , Colposcopia , Técnicas Citológicas , Detecção Precoce de Câncer , Feminino , Seguimentos , Humanos , Programas de Rastreamento/métodos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Guias de Prática Clínica como Assunto , Avaliação de Programas e Projetos de Saúde , Sensibilidade e Especificidade , Suécia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/virologia , Esfregaço VaginalRESUMO
OBJECTIVE: To improve primary prevention of human papillomavirus (HPV) infection by promoting vaccination and increased condom use among upper secondary school students. DESIGN: Cluster randomised controlled trial. SETTING: 18 upper secondary schools in Sweden. PARTICIPANTS: Schools were first randomised to the intervention or the control group, after which individual classes were randomised so as to be included or not. Of the 832 students aged 16 years invited to participate during the regular individual health interview with the school nurse, 751 (90.2%) agreed to participate and 741 (89.1%) students completed the study. INTERVENTIONS: The intervention was based on the Health Belief Model (HBM). According to HBM, a person's health behaviour can be explained by individual beliefs regarding health actions. School nurses delivered 30 min face-to-face structured information about HPV, including cancer risks and HPV prevention, by propagating condom use and HPV vaccination. Students in the intervention and the control groups completed questionnaires at baseline and after 3 months. MAIN OUTCOME MEASURES: Intention to use condom with a new partner and beliefs about primary prevention of HPV, and also specifically vaccination status and increased condom use. RESULTS: All statistical analyses were performed at the individual level. The intervention had a significant effect on the intention to use condom (p=0.004). There was also a significant effect on HBM total score (p=0.003), with a 2.559 points higher score for the intervention group compared to the controls. The influence on the HBM parameters susceptibility and severity was also significant (p<0.001 for both variables). The intervention also influenced behaviour: girls in the intervention group chose to have themselves vaccinated to a significantly higher degree than the controls (p=0.02). No harms were reported. CONCLUSIONS: The school-based intervention had favourable effects on the beliefs about primary prevention of HPV, and increased the HPV vaccination rates in a diverse population of adolescents. TRIAL REGISTRATION NUMBER: NCT02280967; Results.