W. P. Soutter

Invasive cervical cancer after conservative therapy for cervical intraepithelial neoplasia.

BACKGROUND Conservative outpatient therapy for cervical intraepithelial neoplasia (CIN) by ablative or excisional techniques is widely used. The main objective of this treatment is the prevention of invasive cervical cancer. We assessed the rate of invasive disease and the duration of the risk of developing invasive cervical cancer after such treatment. METHODS Four UK centres have used life-table methods to analyse the long-term results of conservative treatment of CIN. We combined and updated data from these studies to investigate the rate of invasive disease after treatment and the duration of that risk. FINDINGS The data comprised 44 699 woman-years of follow-up, with 2116 women under observation 8 years after treatment. 33 women developed invasive cancer, 14 of whom had microinvasion. The cumulative rate of invasion 8 years after treatment was 5.8 per 1000 women and the rate of invasive cancer during this period was 85 (95% CI 60-119) per 100,000 woman-years. The risk of developing cancer did not change throughout the 8 years of follow-up. INTERPRETATION These data show that conservative outpatient therapy in women with CIN reduces the risk of invasive cancer of the cervix by 95% during the first 8 years after treatment. However, even with careful, long-term follow-up, the risk of invasive cervical cancer among these women is about five times greater than that among the general population of women throughout that period. Careful follow-up is essential for at least 10 years after conservative treatment of CIN.

Incomplete excision of cervical intraepithelial neoplasia and risk of treatment failure: a meta-analysis

BACKGROUND Over 60,000 women are treated for cervical intraepithelial neoplasia (CIN) each year in England, most by excision. Management of women who have incomplete excision is controversial and the subject of much debate. Consequently, the completeness of excision is often ignored in the planning of subsequent treatment. We aimed to assess the effect of completeness of excision on the risk of post-treatment disease. METHODS We undertook a meta-analysis of studies published between Jan 1, 1960, and Jan 31, 2007, that studied the risk of post-treatment disease (ie, CIN of any grade or invasive cancer) in relation to completeness of excision. Studies were included if they described treatment of CIN by excision; numbers of women with involved margins; prevalence of and numbers of women with post-treatment disease in relation to margin status. Criteria for post-treatment disease had to be stated as a defined abnormal cytology or histology. Studies were excluded if they described treatment of cervical glandular intraepithelial disease (CGIN); if all or nearly all women had reflex hysterectomy done soon after initial treatment; if women were immunosuppressed (eg, if they were HIV-positive); or if no control group with disease-free margins was used. The endpoint of our analysis was the relative risk (RR) of post-treatment disease in those whose treatment histology suggested that excision was complete compared with those in whom excision was incomplete or uncertain. RR meta-analysis was done by use of a random effects model. FINDINGS The initial Medline search identified 1756 publications, from which 125 publications were short-listed. Of these, 65 and one unpublished study met our inclusion criteria; therefore, 66 studies were included in this meta-analysis. These studies described findings in 35,109 women of whom 8091 (23%) had at least one margin of the excision biopsy involved with disease. After incomplete excision, RR of post-treatment disease of any grade was 5.47 (95% CI 4.37-6.83) and RR of high-grade disease (ie, CIN 2 or 3, or high-grade squamous intraepithelial lesion) was 6.09 (3.87-9.60) compared with the reference group who had complete excision. High-grade post-treatment disease occurred in 597 of 3335 (18%) women who had incomplete excision versus 318 of 12 493 (3%) women who had complete excision. INTERPRETATION Incomplete excision of CIN exposes women to a substantial risk of high-grade post-treatment disease. Some of these women would be safer with a second treatment, especially if deep margins are involved, but most will need close follow-up for at least 10 years. Every effort should be made to avoid incomplete excision. Adding extensive ablation in the treatment crater to compensate for inadequate excision should be avoided because this might delay detection of inadequately treated invasive disease and because the effectiveness of additional ablation to destroy any residual CIN cannot be assessed. Furthermore, extensive ablation does not decrease any risk of preterm delivery in subsequent pregnancies.

Long-term risk of invasive cervical cancer after treatment of squamous cervical intraepithelial neoplasia.

Invasive cancer of the cervix after treatment for cervical intraepithelial neoplasia (CIN) is becoming more important, as screening reduces the incidence of invasive disease. The rate of invasive cervical or vaginal cancer following treatment for CIN in UK remains elevated for at least 8 years. The aim of our study was to determine from international data how long this rate remains elevated and whether the rate of invasive disease reflects the rate of posttreatment CIN. The aim was to determine why the rate of invasive disease does not fall. A search of Medline and a secondary search of cited references identified 1,848 articles referring to the success rate of the treatment of CIN. Only 26 cohorts from 25 articles met all the inclusion criteria. The policy in these was to perform at least annual smears. After the first year following treatment for CIN, the rate of invasive disease remained about 56 per 100,000 woman years until at least 20 years after treatment. This rate is ˜2.8 times greater than expected. In contrast, the risk of posttreatment CIN declined steadily with time to about 190 per 100,000 women in the 10th year. Although the posttreatment rate of CIN falls with time, the rate of invasive disease remains static. It seems likely that this is due to diminishing compliance with follow‐up. Women should be encouraged to persevere with annual smears for at least 10 years after their treatment as this may offer them the best chance of detecting recurrence at a treatable stage.

Comparison of Seven Tests for High-Grade Cervical Intraepithelial Neoplasia in Women with Abnormal Smears: the Predictors 2 Study

ABSTRACT High-risk human papillomavirus (HPV) DNA/RNA testing provides higher sensitivity but lower specificity than cytology for the identification of high-grade cervical intraepithelial neoplasia (CIN). Several new HPV tests are now available for this purpose, and a direct comparison of their properties is needed. Seven tests were evaluated with samples in liquid PreservCyt transport medium from 1,099 women referred for colposcopy: the Hybrid Capture 2 (Qiagen), Cobas (Roche), PreTect HPV-Proofer (NorChip), Aptima HPV (Gen-Probe), and Abbott RealTime assays, the BD HPV test, and CINtec p16INK4a cytology (mtm laboratories) immunocytochemistry. Sensitivity, specificity, and positive predictive value (PPV) were based on the worst histology found on either the biopsy or the treatment specimen after central review. Three hundred fifty-nine women (32.7%) had CIN grade 2+ (CIN2+), with 224 (20.4%) having CIN3+. For detection of CIN2+, Hybrid Capture 2 had 96.3% sensitivity, 19.5% specificity, and 37.4% PPV. Cobas had 95.2% sensitivity, 24.0% specificity, and 37.6% PPV. The BD HPV test had 95.0% sensitivity, 24.2% specificity, and 37.8% PPV. Abbott RealTime had 93.3% sensitivity, 27.3% specificity, and 38.2% PPV. Aptima had 95.3% sensitivity, 28.8% specificity, and 39.3% PPV. PreTect HPV-Proofer had 74.1% sensitivity, 70.8% specificity, and 55.4% PPV. CINtec p16INK4a cytology had 85.7% sensitivity, 54.7% specificity, and 49.1% PPV. Cytology of a specimen taken at colposcopy (mild dyskaryosis or worse) had 88.9% sensitivity, 58.1% specificity, and 50.7% PPV. Our study confirms that, in a referral setting, HPV testing by a number of different tests provides high sensitivity for high-grade disease. Further work is needed to confirm these findings in a routine screening setting.

Long-term follow-up of cervical abnormalities among women screened by HPV testing and cytology—results from the Hammersmith study

Several studies have shown that HPV testing is substantially more sensitive than cytology for primary cervical screening. However, less data exist concerning the duration of protection afforded by a negative HPV test compared to a normal cytological outcome. Here we report the long‐term findings from the Hammersmith study in women aged 35 or more. HPV testing by Hybrid Capture II was performed on all available samples from the baseline screening visit. Passive surveillance of subsequent cytology screening results for the 2,982 women in the study was undertaken using a national registry. Histological outcomes were sought for all women with abnormal smears. The primary outcome was duration of protection against histologically confirmed CIN2+ afforded by a negative HPV test compared to normal cytology. 2,516 women had at least one further smear at least 1 year after entry and 20 new cases of CIN2+ were identified during a median follow‐up of 6.4 years. Including disease identified at baseline, the risk of developing CIN2+ at 1, 5 and 9 years after a normal cytology was 0.33%, 0.83% and 2.20% respectively whereas it was 0.19%, 0.42% and 1.88% after a negative HPV test. HPV testing offered excellent protection from CIN2+ for at least 6 years after a negative test, whereas the protection from cytology began to wane after about 3 years. Substantially more CIN2+ lesions were found in the follow‐up period in those initially HPV positive compared to those HPV negative (HR = 6.52, p = 0.001), whereas there was little difference according to initial cytology (HR = 1.64, p = 0.51).

Is conservative treatment for adenocarcinoma in situ of the cervix safe

Objective To determine the long term results of treatment of adenocarcinoma in situ by conisation of the cervix using survival analysis.

The frequency of significant pathology in women attending a general gynaecological service for postcoital bleeding

Objectives To document the frequency of pathology in women who complain of postcoital bleeding. To determine whether negative cervical cytology excludes serious pathology in women with postcoital bleeding. To determine whether postcoital bleeding increases the risk of serious pathology in women with an abnormal smear.

Dynamic Spectral Imaging: Improving Colposcopy

Purpose: Colposcopy occupies a key role in the prevention of cervical cancer by identifying preinvasive or invasive lesions. However, colposcopy is subjective and is responsible for 52% of screening failures. Dynamic spectral imaging (DSI) is based on the objective, quantitative assessment of the acetowhitening effect. This study compared DSI with colposcopy. Experimental Design: Women referred for colposcopy were examined simultaneously with colposcopy and DSI using a precommercial DySIS model (FPC-03) in an international, multicenter trial. The colposcopy impression and DySIS values were compared with consensus histology reports of biopsies. Subjects were recruited to a training group and subsequently to a test group. Measures were taken to avoid verification bias. Results: The training and test groups comprised 82 and 308 eligible women, respectively. A cutoff value to identify high-grade disease was selected from the results of the training group and data from previous work. Receiver operator curve analysis of the test data showed an area under the curve of 0.844. DySIS detected 62.9% more high-grade cases than colposcopy (57 versus 35, P = 0.0001). DySIS exceeded end points approved by the Food and Drug Administration for similar studies, with increments in the true positive rate of 22/308 (7.1%; lower 95% CL, 4.5% versus 2%) and in the false positive rate of 32/308 (10.4%; upper 95% CL, 14.7% versus 15%). Conclusions: DySIS is more sensitive than colposcopy in detecting high-grade lesions and can provide improved guidance for biopsy. The results are obtained in a user-independent fashion, making it suitable for use by nursing personnel.

Performance of the Abbott RealTime high-risk HPV test in women with abnormal cervical cytology smears.

HPV DNA testing is known to be much more sensitive than cytology, but less specific. A range of HPV and related tests in 858 women referred for colposcopy because of an abnormal smear were evaluated to compare the performances of these tests. This article compared the Abbott test to other tests which had been previously evaluated. This test was a real true test for 14 high‐risk HPV types. The Abbott test was found to be highly sensitive for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) (98.9%) with a specificity of 31.5%. These numbers were comparable with the Qiagen HC2 test, the Roche Linear Array and Amplicor tests, and the Gen‐Probe APTIMA test. Differences between these tests appeared to be related mostly to the choice of cutoff level. An added feature of the Abbott test was the provision of type specific results for HPV 16 and 18. J. Med. Virol. 82: 1186–1191, 2010.

Endometriosis developing during tamoxifen therapy.

Tamoxifen has recently been suggested as treatment for endometriosis. We report a patient who developed endometriosis after starting tamoxifen therapy for benign breast disease.