Louise Smart

After-effects reported by women following colposcopy, cervical biopsies and LLETZ: results from the TOMBOLA trial.

OBJECTIVE Few studies have investigated physical after-effects of colposcopy. We compared post-colposcopy self-reported pain, bleeding, discharge and menstrual changes in women who underwent: colposcopic examination only; cervical punch biopsies; and large loop excision of the transformation zone (LLETZ). DESIGN Observational study nested within a randomised controlled trial. SETTING Grampian, Tayside and Nottingham. POPULATION Nine hundred-and-twenty-nine women, aged 20-59, with low-grade cytology, who had completed their initial colposcopic management. METHODS Women completed questionnaires on after-effects at approximately 6-weeks, and on menstruation at 4-months, post-colposcopy. MAIN OUTCOME MEASURES Frequency of pain, bleeding, discharge; changes to first menstrual period post-colposcopy. RESULTS Seven hundred-and-fifty-one women (80%) completed the 6-week questionnaire. Of women who had only a colposcopic examination, 14-18% reported pain, bleeding or discharge. Around half of women who had biopsies only and two-thirds treated by LLETZ reported pain or discharge (biopsies: 53% pain, 46% discharge; LLETZ: 67% pain, 63% discharge). The frequency of bleeding was similar in the biopsy (79%) and LLETZ groups (87%). Women treated by LLETZ reported bleeding and discharge of significantly longer duration than other women. The duration of pain was similar across management groups. Forty-three percent of women managed by biopsies and 71% managed by LLETZ reported some change to their first period post-colposcopy, as did 29% who only had a colposcopic examination. CONCLUSIONS Cervical punch biopsies and, especially, LLETZ carry a substantial risk of after-effects. After-effects are also reported by women managed solely by colposcopic examination. Ensuring that women are fully informed about after-effects may help to alleviate anxiety and provide reassurance, thereby minimising the harms of screening.

Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy: multicentre randomised controlled trial

Objectives To compare the effectiveness of punch biopsy and selective recall for treatment versus a policy of immediate treatment by large loop excision in the management of women with low grade abnormal cervical cytology referred for colposcopy. Design Multicentre individually randomised controlled trial, nested within the NHS cervical screening programmes. Setting Grampian, Tayside, and Nottingham. Participants 1983 women, aged 20-59, with cytology showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002. Interventions Immediate large loop excision or up to four targeted punch biopsies taken immediately with recall for treatment (by large loop excision) if these showed cervical intraepithelial neoplasia grade II or III or worse. Participants were followed for three years, concluding with an exit colposcopy. Main outcome measures Clinical end points: cumulative incidence of cervical intraepithelial neoplasia grade II or worse and grade III or worse at three years. Clinically significant anxiety and depression and self reported after effects assessed six weeks after colposcopy, biopsies, or large loop excision. Results 879 women (44%) had a normal transformation zone at colposcopy and had no further procedures at that time. Colposcopists were less likely to classify the transformation zone as abnormal when the allocation was large loop excision (603 (60%) in the biopsy and selective recall group; 501 (51%) in the immediate large loop excision group). Of women randomised to biopsy and recall, 157 (16%) required a second clinic visit for treatment. Specimens from almost 60% (n=296) of women who underwent immediate large loop excision showed no cervical intraepithelial neoplasia (31%; n=156) or showed cervical intraepithelial neoplasia grade I (28%; n=140). The percentages of women diagnosed with grade II or worse up to and including the exit examination were 22% (n=216) in the biopsy and recall arm and 23% (n=228) in the immediate large loop excision arm. There was no significant difference between the arms in cumulative incidence of cervical intraepithelial neoplasia grade II or worse (adjusted relative for risk large loop excision v biopsy 1.04, 95% confidence interval 0.86 to 1.25) or grade III or worse (1.03, 0.79 to 1.34). A greater proportion of disease was detected at initial investigation and less during follow-up and at exit in the immediate large loop excision arm, but time of detection did not differ significantly between arms. Levels of anxiety and depression and reported pain did not differ between arms. Higher proportions of women randomised to large loop excision reported moderate or more severe bleeding and discharge. Conclusion A policy of targeted punch biopsies with subsequent treatment for cervical intraepithelial neoplasia grade II or III and cytological surveillance for grade I or less provides the best balance between benefits and harms for the management of women with low grade abnormal cytology referred for colposcopy. Immediate large loop excision results in overtreatment and more after effects and should not be recommended. Trial Registration ISRCTN 34841617.

Persistent infection with human papillomavirus following the successful treatment of high grade cervical intraepithelial neoplasia

In a nested case–control study, we identified women who were successfully treated for CIN 3. Cases had biopsy proven recurrence, whilst controls remained disease free for at least five years. One hundred and seventy‐two women were β‐globin positive at diagnostic biopsy and at six‐month post‐treatment smear (90 controls and 82 cases). Thirty‐nine cases (47.6%) were HPV16/18 positive at biopsy or follow up smear and 14 (17.1%) of 82 were positive at both. Of the controls, 37 (41.1%) were HPV positive at biopsy or smear with 3 (3.3%) positive at both. The unadjusted OR associated with being HPV positive at both points compared to being HPV negative at both was 8.0 (95% CI 2.13–30.37). The persistence of HPV 16/18 infection following the confirmed eradication of CIN is a highly significant risk factor for recurrence.

Pyoderma faciale in a patient with Crohn's disease.

We wish to report the progress of a patient with pyoderma faciale and Crohns disease. The patient is interesting in that on two occasions the relapse in her skin condition coincided with the introduction of non‐steroidal anti‐inflammatory drugs. Therapy with isotretinoin was effective and well tolerated.

Erythema elevatum diutinum–an unusual association with ulcerative colitis

We report the association of erythema elevatum diutinum (EED) with ulcerative colitis (UC). The patient, whose history included rheumatoid disease, diabetes mellitus (type I) and hypothyroidism developed EED during a severe acute exacerbation of UC which resolved following colectomy. To our knowledge this is the first report of such an association. Also of interest was the observation of Köebner phenomenon occurring at the sites where blood vessels were damaged.

The role of human papillomavirus testing in the management of women with low‐grade abnormalities: multicentre randomised controlled trial

Please cite this paper as: Cotton S, Sharp L, Little J, Cruickshank M, Seth R, Smart L, Duncan I, Harrild K, Neal K, Waugh N, The TOMBOLA (Trial Of Management of Borderline and Other Low‐grade Abnormal smears) Group. The role of human papillomavirus testing in the management of women with low‐grade abnormalities: multicentre randomised controlled trial. BJOG 2010; DOI: 10.1111/j.1471‐0528.2010.02519.x.

Who defaults from colposcopy? A multi-centre, population-based, prospective cohort study of predictors of non-attendance for follow-up among women with low-grade abnormal cervical cytology

OBJECTIVE The success of cervical screening relies on women with abnormal cervical cytology attending for follow-up by colposcopy and related procedures. Failure to attend for colposcopy, however, is a common problem in many countries. The objective of this study was to identify factors associated with non-attendance at an initial colposcopy examination among women with low-grade abnormal cervical cytology. STUDY DESIGN A cohort study was conducted within one arm of a multi-centre population-based randomised controlled trial nested within the UK NHS Cervical Screening Programmes. The trial recruited women aged 20-59 years with recent low-grade cervical cytology; women randomised to immediate referral for colposcopy were included in the current analysis (n=2213). At trial recruitment, women completed a socio-demographic and lifestyle questionnaire; 1693 women in the colposcopy arm were also invited to complete a psychosocial questionnaire, including the Hospital Anxiety and Depression Scale. Women were sent up to two colposcopy appointments. A telephone number was provided to reschedule if necessary. Defaulters were defined as those who failed to attend after two appointments. Logistic regression methods were used to compute multivariate odds ratios (OR) to identify variables significantly associated with default. RESULTS 148 women defaulted (6.7%, 95%CI 5.7-7.8%). In multivariate analysis, risk of default was significantly raised in those not in paid employment (OR=2.70, 95%CI 1.64-4.43) and current smokers (OR=1.62, 95%CI 1.12-2.34). Default risk deceased with increasing age and level of post-school education/training and was lower in women with children (OR=0.59, 95%CI 0.35-0.98). Among the sub-group invited to complete psychosocial questionnaires, women who were not worried about having cervical cancer were significantly more likely to default (multivariate OR=1.56, 95%CI 1.04-2.35). Anxiety and depression were not significantly associated with default. CONCLUSIONS Women at highest risk of default from colposcopy are younger, not in paid employment, smoke, lack post-school education, have not had children and are not worried about having cervical cancer. Findings such as these could inform the development of tools to predict the likelihood that an individual woman will default from follow-up. Interventions to minimise default also deserve consideration, but a better understanding of reasons for default is needed to inform intervention development.

The unintended consequences of cervical screening: distress in women undergoing cytologic surveillance.

Objective It is well known that receipt of an initial abnormal cervical cytology test can trigger considerable anxiety among women. Less is known about the impact of follow-up by repeat cytology tests. We quantified prevalence, and identified predictors, of distress after repeat cytologic testing in women with a single low-grade test. Methods Within the framework of the TOMBOLA randomized controlled trial of alternative managements, 844 women aged 20 to 59 years with a single routine cytology test showing borderline nuclear abnormalities (BNA; broadly equivalent to atypical squamous cells of undetermined significance) were assigned to follow-up by repeat cytology in primary care (the first test was due 6 months after the initial BNA result). Women completed sociodemographic and psychosocial questionnaires at recruitment and the Impact of Event Scale (IES) 6 weeks after their first follow-up cytology test. Factors associated with significant psychologic distress (IES ≥ 9) were identified using logistic regression. Results The response rate was 74% (n = 621/844). Of all the respondents, 39% scored in the range for significant distress. Distress varied by follow-up cytology result: negative, 36%; BNA or mild dyskaryosis, 42%; other (including high grade and inadequate), 55%. After adjusting for the cytology result, risk of distress was significantly raised in women who had significant anxiety at recruitment, reported experiencing pain after the follow-up cytology, had children, or were dissatisfied with support they had received after their initial BNA test. Conclusions Substantial proportions of women experience surveillance-related psychologic distress after a follow-up cytology test, even when the result is negative. This is an important, albeit unintended, consequence of cervical screening. Strategies to alleviate this distress merit attention.

Long-term psychosocial impact of alternative management policies in women with low-grade abnormal cervical cytology referred for colposcopy: a randomised controlled trial.

Background:The debate continues regarding the best management for women with low-grade abnormal cervical cytology attending colposcopy. We compared psychosocial outcomes of alternative management policies in these women.Methods:In all, 989 women, aged 20–59 years, with low-grade abnormal cytology, were randomised to immediate large loop excision (LLETZ) or two to four targeted punch biopsies taken immediately with recall for LLETZ if these showed cervical intra-epithelial neoplasia 2/3. At 6 weeks after the last procedure, women completed the hospital anxiety and depression scale (HADS) and the impact of event scale (IES). At 12, 18, 24 and 30 months post recruitment, women completed the HADS and process outcome specific measure (POSM). Prevalence of significant depression (⩾8), significant anxiety (⩾11) and distress (⩾9) and median POSM scores were compared between arms. Multivariate odds ratios (ORs) for immediate LLETZ vs biopsy and recall were computed.Results:Over the entire follow-up, there was no significant difference between arms in cumulative prevalence or risk of significant depression (OR=0.78, 95% CI 0.52–1.17) or significant anxiety (OR=0.83, 95% CI 0.57–1.19). At 6 weeks post procedure, distress did not differ significantly between arms. At later time points, 8–11% had significant depression and 14–16% had significant anxiety but with no differences between arms. The POSM scores did not differ between the arms.Conclusions:There is no difference in long- or short-term psychosocial outcomes of immediate LLETZ and punch biopsies with selective recall.

Which women default from follow-up cervical cytology tests? A cohort study within the TOMBOLA trial.

L. Sharp, S. Cotton, A. Thornton, N. Gray, D. Whynes, L. Smart, N. Waugh, I. Duncan, M. Cruickshank and J. Little, on behalf of the TOMBOLA Group