To compare the cost-effectiveness of different treatments for cervical intraepithelial neoplasia (CIN).
A cost-effectiveness analysis based on data available in the literature and expert opinion.
...England.
Women treated for CIN.
We developed a decision-analytic model to simulate the clinical course of 1000 women who received local treatment for CIN and were followed up for 10 years after treatment. In the model we considered surgical complications as well as oncological and reproductive outcomes over the 10-year period. The costs calculated were those incurred by the National Health Service (NHS) of England.
Cost per one CIN2+ recurrence averted (oncological outcome); cost per one preterm birth averted (reproductive outcome); overall cost per one adverse oncological or reproductive outcome averted.
For young women of reproductive age, large loop excision of the transformation zone (LLETZ) was the most cost-effective treatment overall at all willingness-to-pay thresholds. For postmenopausal women, LLETZ remained the most cost-effective treatment up to a threshold of £31,500, but laser conisation became the most cost-effective treatment above that threshold.
LLETZ is the most cost-effective treatment for both younger and older women. However, for older women, more radical excision with laser conisation could also be considered if the NHS is willing to spend more than £31,500 to avert one CIN2+ recurrence.
Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical and other cancers. Our aim is ...to explore the risk of developing or dying from cervical cancer and other human papillomavirus (HPV)- and non-HPV-related malignancies after CIN treatment and infer its magnitude compared with the general population.
Design: Systematic review and meta-analysis. Eligibility criteria: Studies with registry-based follow-up reporting cancer incidence or mortality after CIN treatment. Data synthesis: Summary effects were estimated using random-effects models.
Incidence rate of cervical cancer among women treated for CIN (per 100 000 woman-years). Relative risk (RR) of cervical cancer, other HPV-related anogenital tract cancer (vagina, vulva, anus), any cancer, and mortality, for women treated for CIN versus the general population.
Twenty-seven studies were eligible. The incidence rate for cervical cancer after CIN treatment was 39 per 100 000 woman-years (95% confidence interval 22–69). The RR of cervical cancer was elevated compared with the general population (3.30, 2.57–4.24; P < 0.001). The RR was higher for women more than 50 years old and remained elevated for at least 20 years after treatment. The RR of vaginal (10.84, 5.58–21.10; P < 0.001), vulvar (3.34, 2.39–4.67; P < 0.001), and anal cancer (5.11, 2.73–9.55; P < 0.001) was also higher. Mortality from cervical/vaginal cancer was elevated, but our estimate was more uncertain (RR 5.04, 0.69–36.94; P = 0.073).
Women treated for CIN have a considerably higher risk to be later diagnosed with cervical and other HPV-related cancers compared with the general population. The higher risk of cervical cancer lasts for at least 20 years after treatment and is higher for women more than 50 years of age. Prolonged follow-up beyond the last screening round may be warranted for previously treated women.
•Women previously treated for CIN are at elevated risk of cervical and other HPV-related neoplasms.•Risk of cervical cancer remains elevated for at least 20 years after treatment.•Prolonged cervical screening beyond current last screening round at 60 or 65 should be considered.•Increased awareness for prevention or early cancer detection of other HPV-related malignancies is needed.
Abstract Objective To assess how the proportion of the cervical volume/length removed during treatment for cervical intraepithelial neoplasia (CIN) varies and whether this correlates to the pregnancy ...duration at delivery. Methods The present prospective observational study included 142 women undergoing CIN treatment at a university hospital during 2009–2013. The pretreatment and post-treatment cervical dimensions and cone size were measured with magnetic resonance imaging, three-dimensional transvaginal ultrasonography, or two-dimensional transvaginal ultrasonography, and the correlation between pregnancy outcomes and the relative proportion of the cervix excised was assessed. Results Pretreatment cervical volumes and cone volumes varied substantially (range 11–40 cm3 and 0.6–8 cm3 , respectively). The proportion of the volume excised ranged from 2.2% to 39.4%. Sixteen (11%) women conceived following treatment; 12 had a live birth (seven at term, three preterm). The pregnancy duration at delivery was significantly correlated with the proportion of the cervical volume ( r = –0.9; P < 0.001) and length ( r = –0.7; P = 0.01) excised and the cone volume ( r = –0.6; P = 0.04). Conclusion The pretreatment cervical dimensions and the proportions of the volume/length excised vary substantially, and the latter correlates with the pregnancy duration. Assessment of the proportion excised might help to stratify women at risk who need intensive surveillance when pregnant.
In a previous phase II trial, we showed that topical imiquimod (IMQ) therapy is an efficacious treatment for high-grade squamous intraepithelial lesion (HSIL). Aim of the present study was to ...investigate the non-inferiority of a 16-week topical, self-applied IMQ therapy compared to large loop excision of the transformation zone (LLETZ) in patients diagnosed with HSIL.
Phase III randomized, controlled, multicenter, open trial performed by Austrian Gynecologic Oncology group. Patients with histologically proven cervical intraepithelial neoplasia (CIN)2 (30 years and older) or CIN3 (18 years and older) and satisfactory colposcopy were randomized to topical IMQ treatment or LLETZ. Successful treatment was defined as negative HPV high-risk test result 6 months after start of the treatment. Secondary endpoints were histological outcome and HPV clearance rates.
Within 3 years 93 patients were randomized, received the allocated treatment and were available for ITT analysis. In the IMQ group negative HPV test at 6 months after treatment start was observed in 22/51 (43.1%) of patients compared to 27/42 (64.3%) in the LLETZ group on ITT analysis (rate difference 21.2%-points, 95% two-sided CI: 0.8 to 39.1). In the IMQ group histologic regression 6 months after treatment was observed in 32/51 (63%) of patients and complete histologic remission was observed in 19/51 (37%) of patients. Complete surgical resection was observed in 84% after LLETZ.
In women with HSIL, IMQ treatment results in lower HPV clearance rates when compared to LLETZ. LLETZ remains the standard for women with HSIL when treatment is required.
Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01283763, EudraCT number: 2012-004518-32.
•The study compared local Imiquimod therapy to LLETZ in patients diagnosed with HSIL.•HPV clearance was observed in 43% and 64% after Imiquimod and LLETZ, respectively.•LLETZ remains the standard therapy for women with HSIL when treatment is required.
The awareness that cervical intra-epithelial neoplasia (CIN) treatment increases the risk of preterm birth has led to major changes in clinical practice. Women with CIN have a higher baseline risk of ...prematurity but local treatment further increases this risk. The risk further increases with increasing cone length and multiplies for repeat excisions; it is unclear whether small cones confer any additional risk to CIN alone. There is no evidence to suggest that fertility is affected by local treatment, although this increases the risk of mid-trimester loss. Caution should prevail when deciding to treat women with CIN of reproductive age. If treatment is offered, this should be conducted effectively to optimise the clearance of disease and minimise the risk of recurrence. Colposcopists should alert women undergoing treatment that this may increase the risk of preterm birth and that they may be offered interventions when pregnant. The cone length should be clearly documented and used as a risk stratifier.
•Women with CIN have a higher baseline risk of prematurity when compared with the general population even without treatment.•Local treatment of CIN significantly increases the risk of preterm birth when compared with having CIN alone.•After excisional treatment there remains a higher risk of CIN recurrence, cervical cancer and other HPV-related malignancies.•Caution should prevail when considering treating women with CIN.•Women should be counselled in colposcopy clinics and advised that they may require additional interventions antenatally.
Objective
To measure anxiety levels in women aged ≥45 years undergoing diagnostic large loop excision of the transformation zone (LLETZ) at the first colposcopy visit.
Design
Longitudinal study.
...Setting
Three colposcopy clinics in the Central Denmark Region.
Population
Women aged ≥45 years undergoing diagnostic LLETZ.
Methods
Women completed the State–Trait Anxiety Inventory (STAI) and Short Form 12 (mental and physical health) questionnaires before, immediately after, and at 1 and 6 months after LLETZ.
Main outcome measures
STAI state anxiety median scores were calculated and stratified by health status, by letter with information about screening result and by LLETZ results.
Results
Of 109 eligible women, 11 were excluded, leaving 98 women for the final analyses. Response rates ranged from 84.7% to 100%. Overall, state anxiety levels were low; however, a decrease was observed from before to immediately after the LLETZ (33.4 vs 29.3, p < 0.001). The anxiety levels remained stable up to 6 months after LLETZ. Women with poor mental health were more likely to have higher anxiety levels compared with women with good mental health (before LLETZ, RR 3.77, 95% CI 2.12–6.70; 1 month after LLETZ, RR 3.37, 95% CI 1.59–7.15; 6 months after LLETZ, RR 1.93, 95%CI 1.06–3.51).
Conclusions
Overall, colposcopy and diagnostic LLETZ in women aged ≥45 years were not associated with high levels of anxiety. Anxiety levels were highest before colposcopy, and the women seemed to experience immediate relief afterwards. Women with poor mental health had the highest anxiety levels throughout the study, which might call for special attention.
Linked article: This article is commented on by Margaret Cruickshank, pp. 201 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471-0528.17336.
The gold standard of cervical intraepithelial neoplasia (CIN) treatment is large loop excision of the transformation zone (LLETZ) after histopathological diagnosis from punch biopsies. In addition, ...treatment may be appropriate at initial colposcopy. Our objective was to study the applicability of immediate treatment strategy according to clinical parameters.
We conducted a prospective cohort study among patients referred to colposcopy at Helsinki University Hospital, Finland, between January 2014, and September 2018 (ISRCTN10933736). Patients treated with LLETZ, either after biopsies or immediately at initial colposcopy, were included. The main outcome measure was overtreatment (OT) rate defined as normal or low-grade histopathological findings in LLETZ specimen within both treatment groups.
A total of 572 patients treated with LLETZ were included: 360 treated after biopsies and 212 treated immediately at initial colposcopy. When LLETZ was performed immediately after high-grade referral cytology and with colposcopic impression of high-grade disease, the overtreatment (OT) rate was 10.0% (95% CI 9.10 to 17.2), whereas when LLETZ was done after biopsy-confirmed high-grade lesions, the OT rate was 18.9% (95% CI 14.7 to 23.7), resulting in risk difference (RD) −8.91% (95% CI −16.0 to −1.82). Among HPV16/18 positive patients the OT rate was 8.22% (95% CI 3.08 to 17.0) for immediate treatment, resulting in RD of −10.7% (95% CI −18.3 to −3.04) compared to LLETZ after biopsies.
Immediate LLETZ does not result in overtreatment when applied on selected cases, especially after high-grade referral cytology and when high-grade lesion is also colposcopically suspected.
•Select-and-treat resulted in lower overtreatment rate than LLETZ after HSIL biopsy.•Immediate treatment of CIN does not increase overtreatment rate if current care guidelines are followed.•If HPV 16/18 was positive, the overtreatment rate was lower after immediate treatment than treatment after HSIL biopsy.•The overtreatment rate was rather high in both treatment groups for patients with type 3 transformation zone.
Background: Cervical dysplasia is the most common gynecological disorder of modern era. It initiates around the squamocolumnar junction of the cervix commonly due to the infection of human papilloma ...virus. Large loop excision of transitional zone is globally a standard procedure of choice both for diagnosing and treating cervical dysplasia. Pap smear is a fast and easy assessment tool for detecting cervical lesions, but it is relatively unreliable.
Methodology: Fifty patients of age group 35 to 65 years patients having normal looking cervix with abnormal pap smear or suspicious looking cervix with or without abnormal pap smear, were selected for the study after informed consent. The procedure for LLTEZ was performed under strict aseptic measures in the procedural room and the biopsy specimen was sent for histopathological examination. The pathological findings were presented as percentages.
Results: 66% cervical biopsy specimens were suggestive of chronic cervicitis and 24% samples were suggestive of chronic cervicitis with squamous metaplasia. Mild dysplasia in 4% samples, moderate and severe dysplasia were seen in 2% samples.
Conclusion: LLETZ is an efficient procedure to deal with cervical dysplasia. It must be recommended for the work-up of uncertain gynecological presentations. The expertise of professionals must be improved through training to obtain maximum benefits.
Background
Loop electrosurgical excision procedure (LEEP) for high‐grade squamous intraepithelial lesion is performed in both an inpatient setting under general anaesthesia and an outpatient setting ...under local anaesthesia. Efficacy and safety are comparable and outpatient LEEP may save time and cost in the Australian setting.
Aims
We aim to compare patient satisfaction with inpatient LEEP compared to outpatient LEEP for Australian best practice.
Materials and Methods
This was a prospective quantitative and qualitative cohort study. An online questionnaire was sent to patients undergoing inpatient and outpatient LEEP to assess satisfaction with the procedure. Further histopathological and demographic data were also collected from the medical records. Groups were compared using Fischer's exact test and pain scores were compared using non‐parametric tests.
Results
Ninety‐three outpatients and 52 inpatients responded to the survey. No difference was found between groups with regard to rate of positive histopathological margins or number of passes required. Outpatients found the procedure to be more convenient than inpatients (P = 0.007), and experienced more pain during the procedure than the inpatient group (P < 0.001). There was no significant difference in pain scores following the procedure or post‐procedure anxiety.
Conclusions
Outpatient LEEP is an acceptable and well‐tolerated procedure, comparable to inpatient LEEP. Regardless of the option chosen, patients are highly likely to be satisfied with their choice. Increased efforts should be made to reduce pre‐procedural anxiety, which may in turn reduce expectations and experiences of pain.
PDF
