Risk of cervical and other cancers after treatment of cervical intraepithelial neoplasia: retrospective cohort study.
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ABSTRACT: Objective
To study the long term risk of cervical and other cancers after treatment for cervical intraepithelial neoplasia.Design
Retrospective cohort study.Setting
University Hospital, Helsinki, Finland.Participants
7564 women treated for cervical intraepithelial neoplasia during 1974 and 2001 and followed up through the Finnish cancer registry until 2003.Main outcome measures
Standardised incidence ratio for cervical cancer and other cancers.Results
During follow-up 22 cases of invasive cervical cancer occurred in women treated for cervical intraepithelial neoplasia (standardised incidence ratio 2.8, 95% confidence interval 1.7 to 4.2). The highest risk was during the second decade (10 cases observed: 3.1, 1.5 to 5.7). The standardised incidence ratio for cervical intraepithelial cancer type 1 was 3.1 (1.4 to 6.2) and for type 2 was 3.7 (0.9 to 10.7).Conclusions
The risk of cervical cancer in the first 20 years after treatment for cervical intraepithelial neoplasia is higher than in the average population. The risk of smoking related cancers is also increased.
SUBMITTER: Kalliala I
PROVIDER: S-EPMC1285099 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose A previous cervical intraepithelial neoplasia is associated with an increased obstetrical risk. It was the aim of the study to identify risk factors of preterm birth in patients with cervical intraepithelial neoplasia in dependence of the treatment modality (excisional vs. ablative). Methods Women with treated cervical intraepithelial neoplasia and subsequent pregnancy (n = 155) were included in this retrospective study. Methods of treatment were either conization by large loop excision of the transformation zone (LLETZ) or ablative laser vaporization. Results Of the total population 60.6% (n = 94) had a conization and 39.4% (n = 61) a laser vaporization alone. The frequency of preterm birth < 37 weeks was 9.7% (n = 15) without differences between conization and laser (11.7 vs. 6.7%, p = 0.407) with an odds ratio (OR) of 1.9 (95% confidence interval [CI] 0.6-6.2). Preterm birth < 34 weeks was found in 2.6% (n = 4), of which all had a conization (4.3 vs. 0%, p = 0.157). Risk factors for preterm birth were repeated cervical intervention (OR 4.7 [95% CI 1.5-14.3]), especially a combination of conization and laser ablation (OR 14.9 [95% CI 4.0-55.6]), age at intervention < 30 years (OR 6.0 [95% CI 1.3-27.4]), a history of preterm birth (OR 4.7 [95% CI 1.3-17.6]) and age at delivery < 28 years (OR 4.7 [95% CI 1.5-14.3]). Conclusion The large loop excision of the transformation zone as a modern, less invasive ablative treatment did not obviously increase the risk of preterm birth compared to laser vaporization. The most important risk factor for preterm delivery was the need of a repeated intervention, especially at younger age. We assume that the persistence or recurrence of the cervical intraepithelial neoplasia following a high-risk human papillomavirus infection is mainly responsible for the observed effect.
| S-EPMC9714382 | biostudies-literature
Project description:ObjectiveTo explore the association between preterm delivery and treatment at colposcopy.DesignRetrospective-prospective cohort study using record linkage.Setting12 National Health Service hospitals in England.ParticipantsWomen who had a cervical histology sample taken between 1987 and 2009. These women were linked by hospital episode statistics to hospital obstetric records between 1998 and 2009 for the whole of England to identify singleton live births between 20-43 gestational weeks before or after cervical histology.Main outcome measuresProportion of preterm births (<37 weeks); the relative risk for the strength of association between preterm births and treatment for cervical intraepithelial neoplasia.Results18,441 singleton births occurred: 4176 before histology and 14,265 after histology. Of the singleton births after histology, 9.0% (n=1284) were preterm compared with 6.7% of all births in England over the same period (excess risk 2.3 per 100 births, 95% confidence interval 1.8% to 2.8%). Among first births after histology, the adjusted relative risk associated with previous treatment was 1.19 (95% confidence interval 1.01 to 1.41); among first births before histology the relative risk associated with subsequent treatment was 1.47 (1.05 to 2.05). Combining these, the relative risk associated with treatment adjusted for timing relative to histology was 0.91 (0.66 to 1.26) corresponding to an absolute difference of -0.25 (-2.61 to 2.11) per 100 singleton births. Among 372 women who gave birth both before and after treatment, there were 30 preterm births after treatment and 32 before treatment (relative risk 0.94, 0.62 to 1.43).ConclusionThe risk of preterm delivery in women treated by colposcopy in England was substantially less than that in many other studies, predominantly from Nordic countries. The increased risk may be a consequence of confounding and not caused by treatment. Although this study is reassuring for large loop excision of the transformation zone overall, it is possible that deep conisation or repeated treatment leads to an increased risk of preterm delivery.
| S-EPMC3421237 | biostudies-literature
Project description:ObjectiveTo compare the risk of cervical cancer in women with histologically confirmed cervical intraepithelial neoplasia who returned to routine screening after having completed post-treatment follow-up with consecutive normal smear test results with women with a normal primary smear test result.DesignPopulation based cohort study using data from a nationwide pathology register.SettingThe Netherlands, 1994 to 2006.Population38,956 women with histologically confirmed intraepithelial neoplasia grades 1 to 3 with completed follow-up after treatment.InterventionRoutine post-treatment follow-up of cervical intraepithelial neoplasia, recommending smear tests at six, 12, and 24 months.Main outcome measureIncidence of cervical cancer in the period from completed follow-up with negative test results after cervical intraepithelial neoplasia to the next primary test. 10-year hazard ratios were compared with periods after normal results for the primary smear test, adjusted for year in follow-up.Results20 cervical cancers were diagnosed during 56,956 woman years after completed follow-up of cervical intraepithelial neoplasia, whereas 1613 cervical cancers were diagnosed during 25,020,697 woman years after a normal primary smear test result. The incidence of 35.1 (95% confidence interval 21.4 to 54.2) per 100,000 woman years and 6.4 (6.1 to 6.8) per 100,000 woman years, respectively, led to an adjusted hazard ratio of 4.2 (95% confidence interval 2.7 to 6.5) for periods after completed follow-up compared with periods after normal primary smear test results. This hazard ratio was increased for all ages. No significant difference in risk of cervical cancer was observed by grade of cervical intraepithelial neoplasia.ConclusionsAn excess risk of cervical cancer previously observed for women treated for cervical intraepithelial neoplasia was also observed in the subgroup of women who completed their post-treatment follow-up with three consecutive normal smear test results. The overall corrected risk of cervical cancer in these women was increased fourfold 35 cases per 100,000 woman years) compared with women with normal primary smear test results (6 per 100,000 woman years).
| S-EPMC3487103 | biostudies-literature
Project description:BACKGROUND:The aim was to estimate the risk of subsequent extra-cervical Human Papillomavirus (HPV) related cancer in patients surgically treated for high grade cervical intraepithelial neoplasia (CIN 2-3). This is the first study in Italy investigating the occurrence of extra-cervical tumors in this cohort of patients. METHODS:3184 patients surgically treated for CIN2-3 since 1992 at the Department of Surgical Sciences of University of Torino were considered. The risk of HPV-related cancer was calculated as Standardized Incidence Ratio (SIR), using as expected values tumour age specific incidence of resident population. RESULTS:173?second primary cancer (SCPs) were identified. SIR to develop cancer after treatment for CIN2-3 was 2.2 (CI 95% 1.89-2.50). Among these occurrences, 10 are in HPV related sites: 1 anus (SIR?=?1.8; 0.04-10.0), 3 vagina (SIR?=?12.4; 2.56-36.3), 1 vulva (SIR?=?1.7; 0.04-9.59), 5 oropharynx (SIR?=?8.5; 2.76-19.8). Significant risk has been also recorded for pulmonary (SIR?=?3.1; 0.70-5.27) and bladder (SIR?=?4.05; 1.10-10.56), with smoking as possible cofactor. We also found increased risk for breast (SIR?=?2.4; 2.07-2.84) and ovarian cancers (SIR?=?2.1; 1.13-3.49), probably due to an higher adherence to spontaneous and programmed screening programs. CONCLUSIONS:Our study supports the hypothesis of an increased risk of HPV-related tumours for CIN treated patients, mostly for CIN3. It is conceivable the need of early diagnosis for these cancers in this higher-risk populations.
| S-EPMC7542855 | biostudies-literature
Project description:BackgroundInformation on the long-term risk of cervical intraepithelial neoplasia (CIN) recurrence among women treated for CIN is limited yet critical for evidence-based surveillance recommendations.MethodsWe retrospectively identified 37,142 women treated for CIN 1, 2, or 3 from January 1, 1986, through December 31, 2000 (CIN cohort), from the British Columbia Cancer Agency cytology database and linked their records with cancer registry and vital statistics data. Treatment included cryotherapy, loop electrosurgical excision procedure, cone biopsy, and laser vaporization or excision. A comparison cohort contained 71,213 women with normal cytology and no previous CIN diagnosis. Follow-up continued through December 31, 2004. Among women in both cohorts under active surveillance, we compared rates of CIN 2 or 3 (CIN 2/3) and cervical cancer. Cumulative incidence rates of CIN 2/3 and 95% confidence intervals (CIs) were estimated by a life table approach by using annual rates. Cumulative rates of invasive cancer were examined by the person-years method.ResultsOverall observed cumulative rates of CIN 2/3 in the first 6 years after treatment were 14.0% (95% CI = 13.84% to 14.15%) for women originally treated for CIN 3, 9.3% (95% CI = 9.09% to 9.42%) for CIN 2, and 5.6% (95% CI = 4.91% to 5.21%) for CIN 1. Annual rates of CIN 2/3 were less than 1% after 6 years. Initial diagnosis, age, and treatment type were associated with a diagnosis of CIN 2/3 after treatment, with 6-year adjusted rates for women aged 40-49 years ranging from 2.6% (95% CI = 1.9% to 3.4%) for treatment of CIN 1 with the loop electrosurgical excision procedure to 34.0% (95% CI = 30.9% to 37.1%) for treatment of CIN 3 with cryotherapy. Overall incidence of invasive cancer (per 100,000 woman-years) was higher in the CIN cohort (37 invasive cancers, 95% CI = 30.6 to 42.5 cancers) than in the comparison cohort (six cancers, 95% CI = 4.3 to 7.7 cancers). Cryotherapy, compared with other treatments, was associated with the highest rate of subsequent disease (adjusted odds ratio for invasive cancer = 2.98, 95% CI = 2.09 to 4.60).ConclusionRisk of CIN 2/3 after treatment was associated with initial CIN grade, treatment type, and age. Long-term risk of invasive cancer remained higher among women treated for CIN, particularly those treated with cryotherapy.
| S-EPMC2684554 | biostudies-literature
Project description:Few studies have investigated the absence of high-grade cervical intraepithelial neoplasia (CIN) in excised specimens, and sample sizes of these studies were limited. This study retrospectively analyzed clinical characteristics of 1695 patients with CIN 2/3 to determine the incidence rate and relative factors of CIN 1 or less in conization specimens from patients with colposcopic biopsy-confirmed CIN 2/3. The study group comprised 430 cases of CIN 1 or less in conization specimens, and the control group comprised 1142 cases with high-grade CIN lesions in conization specimens. Univariate and multivariate logistic regression models were established to evaluate relative factors. The 1-9 years follow-up data were analyzed to determine the persistence/recurrence rate. Multivariate logistic regression showed that patients aged 18-24 years (OR (95% CI) = 2.224 (1.014, 4.877)); with a negative hrHPV test result (OR (95% CI) = 3.210 (1.627, 6.331)); a cytology test result of normal (OR (95% CI) = 5.184 (3.138, 8.563)), ASC-US (OR (95% CI) = 3.420 (2.102, 5.564)), LSIL (OR (95% CI) = 2.588 (1.475, 4.541)), or ASC-H (OR (95% CI) = 2.434 (1.306, 4.539)); an indication of CIN 2 on biopsy (OR (95% CI) = 2.290 (1.694, 3.096)), and no glandular involvement (OR (95% CI) = 1.616 (1.205, 2.169)) were more likely to have an absence of high-grade dysplasia in conization specimens. There was no difference in the persistence/recurrence rate between the two groups (x2 = 1.55, P = 0.46). An age of 18-24 years, a negative hrHPV test result, a non-HSIL cytology test result, an indication of CIN 2 on biopsy, and no glandular involvement were relative factors for an absence of high-grade dysplasia in conization specimens. For patients with relative factors, especially young women, informed follow-up should be considered.
| S-EPMC9515539 | biostudies-literature
Project description:OBJECTIVE:To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements. METHODS:Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152). RESULTS:There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07-0.68; p=0.010). Women in their 40s-50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03-1.49; p=0.020). CONCLUSION:In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years.
| S-EPMC5981106 | biostudies-literature
Project description:Background DNA methylation is an essential factor in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer. The aim was to investigate the diagnostic value provided by methylation biomarkers of six tumor suppressor genes (ASTN1, DLX1, ITGA4, RXFP3, SOX17 and ZNF671) for cervical precancerous lesions and cervical cancer. Methods The histological cervical specimens of 396 cases including 93 CIN1, 99 CIN2, 93 CIN3 and 111 cervical cancers were tested for methylation-specific PCR assay (GynTect®) of score and positive rate. Among them, 66 CIN1, 93 CIN2, 87 CIN3 and 72 cervical cancers were further used for paired analysis. A chi-square test was used to analyze the difference of methylation score and positive rate in cervical specimens. The paired t-test and paired chi-square test were for analyzing the methylation score and positive rate in paired CIN and cervical cancer cases. The specificity, sensitivity, odds ratio (OR) and 95% confidence interval (95% CI) of the GynTect® assay for CIN2 or worse (CIN2 +) and CIN3 or worse (CIN3 +) were evaluated. Results According to the chi-square test trend, hypermethylation increased with severity of the lesions as defined by histological grading (P = 0.000). The methylation score above 1.1 was more common in CIN2 + than in CIN1. The DNA methylation scores in the paired groups of CIN1, CIN3 and cervical cancer were significant differences (P = 0.033, 0.000 and 0.000, respectively), except for CIN2 (P = 0.171). While the positive rate of GynTect® in each paired group had no difference (all P > 0.05). The positive rate of every methylation marker in the GynTect® assay showed differences in four cervical lesion groups (all P < 0.05). The specificity of GynTect® assay for detection of CIN2 + /CIN3 + were higher than high-risk human papillomavirus test. With CIN1 as a reference, the positive status of GynTect®/ZNF671 were significantly higher in CIN2 + : odds ratio (OR) 5.271/OR 13.909, and in CIN3 + : OR 11.022/OR 39.150, (all P < 0.001). Conclusion The promoter methylation of six tumor suppressor genes is related to the severity of cervical lesions. The GynTect® assay based on cervical specimens provides diagnostic values for detecting CIN2 + and CIN3 + . Supplementary Information The online version contains supplementary material available at 10.1186/s12885-023-10628-5.
| S-EPMC9940376 | biostudies-literature
Project description:Human papillomavirus (HPV)-associated lesions and malignancies exhibit alterations in the composition and functionality of the extracellular matrix (ECM) that represent the complex molecular pathways present between infection and disease. A total of 20 urine samples were used, including from 10 patients with cervical intraepithelial neoplasia grade 3 (CIN3) and 10 healthy controls to perform the label-free quantitative analysis using the nano-HPLC and ESI-MS ion trap mass analyzer and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF/MS) fast screening. Among 476 identified/quantified proteins, 48 were significantly changed (log2-fold change ≥1.0 or ≤-1.0, -log10 (bbinominal, p-value ≥ 1.3), of which were 40 proteins (down-regulated) and 8 proteins (up-regulated) in CIN3, in comparison to healthy controls. The biological function and key pathway enrichment of the gene set using gen set enrichment analysis (GSEA) were analyzed. The ECM-receptor interaction pathway (NES = -1.64, p = 0.026) was down-regulated by 13 proteins (HSPG2, COL6A1, COL6A3, SPP1, THBS1, TNC, DAG1, FN1, COMP, GP6, VTN, SDC1, and CD44; log2 FC range from -0.03 to -1.48) for the CIN3 group in the KEGG database. The MALDI-TOF/MS screening showed the difference of protein profiles between the control and CIN3 groups, i.e., using the scatter plot with a well-separated shape, as well as effectively distinguishing both groups (control and CIN3) using genetic algorithms (GA) with cross-validation (51.56%) and recognition capability (95.0%). Decreased levels of ECM-receptor interaction proteins may cause disturbances in the interactions of cells with the ECM and play an important role in the development and progression of cervical cancer.
| S-EPMC9916937 | biostudies-literature
Project description: Not available
| S-EPMC6457789 | biostudies-literature