| 1. |
- Alder, Susanna, et al.
(författare)
-
Incomplete excision of cervical intraepithelial neoplasia as a predictor of the risk of recurrent disease : a 16-year follow-up study
- 2020
-
Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier. - 0002-9378 .- 1097-6868. ; 222:2, s. 172.e1-172.e12
-
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.
|
|
| 2. |
- Alder, Susanna
(författare)
-
Prevention of cervical cancer in countries with high and low incidence of the disease
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cervical cancer is to a large extent a preventable disease, through prophylactic human papillomavirus (HPV) vaccination and cervical cancer screening. Still, it is the second most common cancer among women in Argentina, with unchanged mortality rates for the last 30 years, due to the absence of organized screening. In Sweden, with a well-organized screening program, cervical cancer burden is lower; however, the incidence is increasing again. This thesis has explored several aspects of cervical cancer prevention in different settings. The overall aim of this thesis is to improve cervical cancer prevention by contributing knowledge on i) vaccination acceptance, ii) barriers to screening and iii) the risk of recurrent/residual disease among women treated for precancerous lesions. Study I explored HPV vaccination acceptance among 174 young women aged 18-30 years from the Mendoza Province, Argentina, by using a structured questionnaire-based interview technique. HPV vaccination acceptance was at high 95%, and 75% stated that they were also willing to pay for vaccination. A statistically significant positive association was found between acceptance and belief in vaccine safety, and a statistically significant negative association between being a welfare recipient and acceptance if vaccination was not free. Educational campaigns ensuring the safety of vaccines, as well as clarifying other misconceptions are needed. Study II investigated maternal HPV vaccination acceptance among 180 mothers to girls aged 9-15 years from the Mendoza province, Argentina, through use of a structured survey. HPV vaccination acceptance was 90% if it was free of charge, and 60% if it was not free. Being gainfully employed and having a higher disposable household income was significantly associated with acceptance of vaccination if it was not free, which suggests that cost could be an obstacle to catch-up vaccination and may lead to socioeconomic inequalities in uptake. Also, women with prior awareness of cervical cancer were more willing to pay for HPV vaccination, indicating the importance of improving awareness of HPV and its related diseases. Study III explored barriers and facilitators of screening compliance among 1510 women attending cervical cancer screening in Stockholm, Sweden through use of a structured survey. The mean total time and travel costs and direct non-medical cost per attendance were €55.6. Nearly half (44%) of the women did not attend screening within 1 year from their invitation, of which 51% cited difficulties in taking time off work. The most important correlates of higher screening compliance were not needing to take time off work, not having a companion and being of higher HPV knowledge. Increased flexibility by extended opening hours and improved general knowledge of HPV may facilitate screening compliance. Study IV investigated the long-term risk of recurrent or residual disease in relation to surgical margin status among 991 women who had undergone conization treatment of high-grade precancerous lesions at the Karolinska University Hospital in Sweden during 2000-2007. During a median of 10 years follow-up, 12% were diagnosed with residual or recurrent disease, based on data from the Swedish National Cervical Screening Registry. Women with involved margins had significantly worse outcomes compared to women with negative margins. The risk was almost 3-fold higher among women with involved endocervical margins, involved margins and uncertain as to whether these were endocervical or ectocervical, and especially when both margins were involved. These findings suggest that stratified margin status may contribute to the safety of the follow-up surveillance. In conclusion; this thesis provides improved knowledge on what may constitute barriers to HPV vaccination and cervical cancer screening, and delineates possible strategies on how to increase uptake of these prevention strategies. Ensuring the safety of HPV vaccines and educational campaigns on HPV and its related diseases appear important targets for achieving higher uptake. Also, our findings suggest that costs can be a barrier, both in the Argentinean setting, as well as to participation in cervical cancer screening in Sweden. It is thus important that the screening organization facilitates the participation of all women in Sweden, including all socioeconomic groups. Finally, the thesis shows that women treated for precancerous lesions with involved surgical margins are at high-risk of recurrent disease and differential risks could be shown with respect to which margin was affected. Future research should address the accuracy of combining margins status with established followup surveillance.
|
|
| 3. |
- Andersson, Sonia, et al.
(författare)
-
Age, margin status, high-risk human papillomavirus and cytology independently predict recurrent high-grade cervical intraepithelial neoplasia up to 6 years after treatment
- 2021
-
Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 22:3
-
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.
|
|
| 4. |
- Belkić, Karen, et al.
(författare)
-
Predictors of treatment failure for adenocarcinoma in situ of the uterine cervix : Up to 14 years of recorded follow-up
- 2022
-
Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 24:4
-
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.
|
|
