| 1. |
- Alder, Susanna, et al.
(författare)
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Incomplete excision of cervical intraepithelial neoplasia as a predictor of the risk of recurrent disease : a 16-year follow-up study
- 2020
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier. - 0002-9378 .- 1097-6868. ; 222:2, s. 172.e1-172.e12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Women treated for high-grade cervical intraepithelial neoplasia (CIN, grade 2 or 3) are at elevated risk of developing cervical cancer. Suggested factors identifying women at highest risk for recurrence post-therapeutically include incomplete lesion excision, lesion location, size and severity, older age, treatment modality and presence of high-risk human papilloma virus (hrHPV) after treatment. This question has been intensively investigated over decades, but there is still substantial debate as to which of these factors or combination of factors most accurately predict treatment failure.OBJECTIVES: In this study, we examine the long-term risk of residual/recurrent CIN2+ among women previously treated for CIN2 or 3 and how this varies according to margin status (considering also location), as well as comorbidity (conditions assumed to interact with hrHPV acquisition and/or CIN progression), post-treatment presence of hrHPV and other factors.STUDY DESIGN: This prospective study included 991 women with histopathologically-confirmed CIN2/3 who underwent conization in 2000-2007. Information on the primary histopathologic finding, treatment modality, comorbidity, age and hrHPV status during follow-up and residual/recurrent CIN2+ was obtained from the Swedish National Cervical Screening Registry and medical records. Cumulative incidence of residual/recurrent CIN2+ was plotted on Kaplan-Meier curves, with determinants assessed by Cox regression.RESULTS: During a median of 10 years and maximum of 16 years follow-up, 111 patients were diagnosed with residual/recurrent CIN2+. Women with positive/uncertain margins had a higher risk of residual/recurrent CIN2+ than women with negative margins, adjusting for potential confounders (hazard ratio (HR)=2.67; 95% confidence interval (CI): 1.81-3.93). The risk of residual/recurrent CIN2+ varied by anatomical localization of the margins (endocervical: HR=2.72; 95%CI: 1.67-4.41) and both endo- and ectocervical (HR=4.98; 95%CI: 2.85-8.71). The risk did not increase significantly when only ectocervical margins were positive/uncertain. The presence of comorbidity (autoimmune disease, human immunodeficiency viral infection, hepatitis B and/or C, malignancy, diabetes, genetic disorder and/or organ transplant) was also a significant independent predictor of residual/recurrent CIN2+. In women with positive hrHPV findings during follow-up, the HR of positive/uncertain margins for recurrent/residual CIN2+ increased significantly compared to women with hrHPV positive findings but negative margins.CONCLUSIONS: Patients with incompletely excised CIN2/3 are at increased risk of residual/recurrent CIN2+. Margin status combined with hrHPV results and consideration of comorbidity may increase the accuracy for predicting treatment failure.
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| 2. |
- Andersson, Sonia, et al.
(författare)
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Age, margin status, high-risk human papillomavirus and cytology independently predict recurrent high-grade cervical intraepithelial neoplasia up to 6 years after treatment
- 2021
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 22:3
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Tidskriftsartikel (refereegranskat)abstract
- The present study aimed to identify the factors that independently contribute to disease recurrence among women first-time treated for high-grade cervical intraepithelial neoplasia (CIN) during 4-6 years of follow-up. Overall, 529 of 530 eligible patients participated; these patients all attended a 1st follow-up appointment similar to 6 months post-conization, at which time high-risk human-papillomavirus (HPV) testing, liquid-based cytology and colposcopy were performed. Full data on margin excision status, other aspects of initial treatment and comorbidity were obtained. At least one subsequent follow-up was attended by 88% of patients. A total of 22 recurrent cases were detected during follow-up. Detected recurrence was the outcome of focus for multiple logistic regression analysis, with odds ratios (OR) and 95% confidence intervals (CI) computed. Four significant independent risk factors were identified: Age 45 years or above (OR=3.5, 95% CI=1.3-9.9), one or both unclear or uncertain margins (OR=5.3, 95% CI=2.0-14.2), positive HPV at 1st follow-up (OR=5.8, 95% CI=2.0-16.8), and abnormal cytology at 1st follow-up (OR=3.9, 95% CI=1.4-11.0). Bivariate analysis revealed that persistent HPV positivity was associated with recurrence (P<0.01). These findings indicated that incomplete excision of the CIN lesion may warrant more intensive subsequent screening, regardless of early post-conization HPV findings. Although early post-conization positive HPV was a powerful, independent predictor of recurrent high-grade CIN, over one-third of the patients with detected recurrence had a negative early post-conization HPV finding. These patients returned for routine screening, at which time, in most cases, HPV status was positive, thus indicating the need for repeated HPV evaluation. Especially during the on-going pandemic, home vaginal self-sampling is recommended. Particular attention is required for women aged >= 45 years. In addition, although not statistically significant, relevant comorbidities, especially autoimmune conditions, warrant consideration in clinical decision-making. Women who have been treated for high-grade CIN are at risk for recurrent disease and progression to cervical cancer; therefore, they require careful, individualized follow-up to avoid these adverse consequences.
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| 3. |
- Belkić, Karen, et al.
(författare)
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Predictors of treatment failure for adenocarcinoma in situ of the uterine cervix : Up to 14 years of recorded follow-up
- 2022
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 24:4
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of adenocarcinoma-in-situ (AIS) of the uterine cervix is rising, with invasive adenocarcinoma becoming increasingly common relative to squamous cell carcinoma. The present study reviewed a cohort of 84 patients first-time treated by conization for histologically-confirmed AIS from January 2001 to January 2017, to identify risk factors associated with recurrent/persistent AIS as well as progression to invasive cervical cancer. Nearly 80% of the patients were age 40 or younger at conization. Endocervical and ectocervical margins were deemed clear in 42 of the patients. All but two patients had ≥1 follow-up, with post-conization high-risk human papilloma virus (HPV) results documented in 52 patients. Altogether, 12 histopathologically-confirmed recurrences (14.3%) were detected; two of these patients had microinvasive or invasive carcinoma. In three other patients cytology showed AIS, but without recorded histopathology. Eight patients underwent hysterectomy for incomplete resection very soon after primary conization; they were not included in bivariate or multivariate analyses. Having ≥1 post-follow-up positive HPV finding yielded the highest sensitivity for histologically-confirmed recurrence: 87.5 [95% confidence interval (CI) 47.4-99.7]. Current or historical smoking status provided highest specificity: 94.4 (95% CI 72.7-99.9) and overall accuracy: 88.0 (95% CI 68.8-97.5) for histologically-confirmed recurrence. With multiple logistic regression (MLR), adjusting for age at conization and abnormal follow-up cytology, positive HPV18 was the strongest predictor of histologically-confirmed recurrence (P<0.005). Having ≥2 positive HPV results also predicted recurrence (P<0.02). Any unclear margin yielded an odds ratio 7.21 (95% CI 1.34-38.7) for histologically-confirmed recurrence adjusting for age, but became non-significant when including abnormal cytology in the MLR model. The strong predictive value of HPV, particularly HPV18 and persistent HPV positivity vis-à-vis detected recurrence indicated that regular HPV testing for patients treated for AIS is imperative. In conclusion, furthering a participatory approach, including attention to smoking with encouragement to attend needed long-term follow-up, can better protect these patients at high risk for cervical cancer.
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| 4. |
- Megyessi, David
(författare)
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Suggested next steps to prevent cervical cancer after surgical treatment for high-grade cervical dysplasia
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The risk of cervical cancer among women treated for high-grade cervical dysplasia is more than twofold compared with the general population, and this risk remains elevated for over two decades. In Sweden, cervical cancer incidence is rising again and the risk of cervical cancer among women with a prior history of high-grade cervical dysplasia has increased since the 1960s. The surgical procedure known as conization is commonly used to treat high-grade cervical dysplasia and prevent progression to invasive cervical cancer. However, treatment failure, defined as residual/recurrent/ high-grade cervical dysplasia or cervical cancer post-conization, has reportedly increased by almost twenty percent. Suggested risk-factors for post-conization treatment failure include age, smoking, treatment modality, lesion size and severity, incomplete excision of lesion, infection with high-risk human papilloma virus (hrHPV) and hrHPV persistence. The overarching aim of this thesis addresses how to protect women from developing cervical cancer following treatment of high-grade cervical dysplasia. The included studies examine risk factors for recurrent disease and what factors or combinations thereof can accurately predict treatment failure and thereby identify women at high risk post-conization. Study I investigated the long-term risk of residual/recurrent high-grade cervical dysplasia post-conization and how such risk varies according to margin status, comorbidity and HPV infection. The study included a total of 991 women who had undergone conization for high-grade cervical dysplasia between 2000 and 2007. Data were obtained from medical records and the Swedish National Cervical Screening Registry (NKCx). Given a median follow-up of ten years and maximum of sixteen years, almost twelve percent of the cohort was diagnosed with residual/recurrent disease or worse (invasive cervical cancer). A greater than 2.5-fold risk of recurrent disease was found among women with incomplete resection compared with cases where the margins were clear. Risk varied according to the extent of anatomical infiltration of disease margins and was particularly elevated when endocervical margins were positive. Comorbidities such as autoimmune disease, HIV, hepatitis B and/or C, malignancy, diabetes, and genetic disorder and/or organ transplantation were independent predictors of recurrent disease. For the subgroup of women who were hrHPV positive with involved margins, risk of recurrent disease was increased compared with the subgroup of women who were HPV positive with clear margins. Women with incompletely resected precancerous lesions are at increased risk for recurrent/residual high-grade cervical dysplasia and cervical cancer. Combined assessment of margin and hrHPV status, while also taking comorbidities into account, may provide a useful strategy to accurately identify at-risk women who should undergo reconization. Study II evaluated risk of recurrent disease among women who had undergone first-time treatment for high-grade cervical dysplasia, within a cohort where complete HPV status was known. A total of 529 women were included, all of whom had undergone conization for high-grade cervical dysplasia between 2014 and 2017. Follow-up continued for up to six years post-conization, during which time 22 patients were diagnosed with recurrence of high-grade cervical dysplasia. Four significant independent risk factors for recurrence were identified: age 45 or older, involved margins, positive hrHPV test at first follow-up and abnormal cytology at first follow-up. Furthermore, persistent hrHPV infection was associated with recurrent disease. The finding that involved margins are an independent risk factor suggests that more intense follow-up is required for these women, regardless of early HPV status post-conization. Although early HPV-positive status post-treatment was found to be a strong independent risk factor for predicting recurrent disease, more than 30% of the 22 patients diagnosed with recurrent disease were HPV-negative shortly after treatment. These patients, however, were subsequently found to be HPV-positive on routine screening, suggesting that repeated HPV testing is necessary during post-conization follow-up. Study III explored risk factors for recurrent/persistent adenocarcinoma-in-situ (AIS), as well as risk factors for progression from AIS to invasive cervical cancer among women who had previously undergone conization for AIS. A total of 84 women who had primary treatment with conization for AIS between 2001 and 2017 were included. Twelve women developed recurrent disease, two of whom had invasive cervical cancer. Among all factors, one or more positive HR-HPV assays post-conization provided the highest sensitivity for predicting recurrence, while smoking or past history of smoking were associated with the highest specificity for recurrence. When adjusting for age at conization and abnormal cytology at follow-up, we demonstrated that HPV18 positive status was the strongest predictor for post-conization recurrence. Two or more positive HPV results post-conization helped predict recurrence. The strong predictive value of HPV in relation to recurrence, especially HPV18, indicates that HPV testing during post-treatment follow-up for AIS is necessary. In addition, it is important to consider smoking status and to encourage long-term follow-up so as to better protect these women who are at high risk of recurrence and progression to invasive cervical cancer. In conclusion, this thesis improves our understanding of what risk factors are able to accurately predict treatment failure and how to identify women at risk of recurrent disease after treatment. This thesis highlights the importance of individualized long-term follow-up, including evaluation of margin status based on residual tumor classification, the need for repeated HPV testing during follow-up and attention to comorbidities.
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