Health-related quality of life in women after colposcopy: results from a longitudinal patient survey.

BACKGROUND: Information concerning the health-related quality-of-life (HRQoL) consequences of colposcopy is limited, particularly over time. In a longitudinal study, we investigated women's HRQoL at 4, 8 and 12 months post colposcopy and the factors associated with this. METHODS: Women attending colposcopy at two large hospitals affiliated with the national screening programme in Ireland were invited to complete questionnaires at 4, 8 and 12 months post colposcopy. HRQoL was measured using the EQ-5D-3L and compared across a range of socio-demographic, clinical and attitudinal variables. A mixed-effects logistic multivariable model was employed to investigate associations between these variables and low HRQoL. RESULTS: Of 584 women initially recruited, 429, 343 and 303 completed questionnaires at 4, 8 and 12 months, respectively. The mean overall HRQoL score for the sample across all time points was 0.90 (SD 0.16). Approximately 18% of women experienced low HRQoL at each of the three time points. In multivariable testing, over the entire 12-month follow-up period, non-Irish nationals (OR 8.99, 95% CI 2.35-34.43) and women with high-grade referral cytology (OR 2.78, 95% CI 1.08-7.13) were at higher odds of low HRQoL. Women who were past (OR 0.20, 95% CI 0.07-0.58) or never (OR 0.42, 95% CI 0.16-1.12) smokers were at lower odds of low HRQoL than current smokers. As women's satisfaction with their healthcare increased their odds of experiencing low HRQoL fell (OR per unit increase 0.51, 95% CI 0.34-0.75). CONCLUSIONS: Women's HRQoL did not change over the 12 months post colposcopy, but some subgroups of women were at higher risk of experiencing low HRQoL. These subgroups may benefit from additional support.

Physical after-effects of colposcopy and related procedures, and their inter-relationship with psychological distress: a longitudinal survey.

OBJECTIVE: To estimate prevalence of post-colposcopy physical after-effects and investigate associations between these and subsequent psychological distress. DESIGN: Longitudinal survey. SETTING: Two hospital-based colposcopy clinics. POPULATION: Women with abnormal cytology who underwent colposcopy (±related procedures). METHODS: Questionnaires were mailed to women 4, 8 and 12 months post-colposcopy. Details of physical after-effects (pain, bleeding and discharge) experienced post-colposcopy were collected at 4 months. Colposcopy-specific distress was measured using the Process Outcome-Specific Measure at all time-points. Linear mixed-effects regression was used to identify associations between physical after-effects and distress over 12 months, adjusting for socio-demographic and clinical variables. MAIN OUTCOME MEASURES: Prevalence of post-colposcopy physical after-effects. Associations between the presence of any physical after-effects, awareness of after-effects, and number of after-effects and distress. RESULTS: Five-hundred and eighty-four women were recruited (response rate = 73, 59 and 52% at 4, 8 and 12 months, respectively). Eighty-two percent of women reported one or more physical after-effect(s). Multiple physical after-effects were common (two after-effects = 25%; three after-effects = 25%). Psychological distress scores declined significantly over time. In adjusted analyses, women who experienced all three physical after-effects had on average a 4.58 (95% CI: 1.10-8.05) higher distress scored than those who experienced no after-effects. Women who were unaware of the possibility of experiencing after-effects scored significantly higher for distress during follow-up. CONCLUSIONS: The prevalence of physical after-effects of colposcopy and related procedures is high. The novel findings of inter-relationships between awareness of the possibility of after-effects and experiencing multiple after-effects, and post-colposcopy distress may be relevant to the development of interventions to alleviate post-colposcopy distress. TWEETABLE ABSTRACT: Experiencing multiple physical after-effects of colposcopy is associated with psychological distress.

Triage of LSIL/ASC-US with p16/Ki-67 dual staining and human papillomavirus testing: a 2-year prospective study.

OBJECTIVE: To investigate human papillomavirus (HPV) DNA testing and p16/Ki-67 staining for detecting cervical intraepithelial grade 2 or worse (CIN2+) and CIN3 in women referred to colposcopy with minor abnormal cervical cytology low-grade squamous intraepithelial lesions (LSIL) and atypical squamous cells of undermined significance (ASC-US). The clinical performance of both tests was evaluated as stand-alone tests and combined, for detection CIN2+ and CIN3 over 2 years. METHODS: ThinPrep(®) liquid-based cytology (LBC) specimens were collected from 1349 women with repeat LSIL or ASC-US. HPV DNA was performed using Hybrid Capture. Where adequate material remained (n = 471), p16/Ki-67 overexpression was assessed. Clinical performance for detection of histologically diagnosed CIN2+ and CIN3 was calculated. RESULTS: Approximately 62.2% of the population were positive for HPV DNA, and 30.4% were positive for p16/Ki-67. p16/Ki-67 showed no significant difference in positivity between LSIL and ASC-US referrals (34.3% versus 28.6%; P = 0.189). Women under 30 years had a higher rate of p16/Ki-67 compared to those over 30 years (36.0% versus 26.6%; P = 0.029). Overall HPV DNA testing produced a high sensitivity for detection of CIN3 of 95.8% compared to 79.2% for p16/Ki-67. In contrast, p16/Ki-67 expression offered a higher specificity, 75.2% versus 40.4% for detection of CIN3. Combining p16/Ki-67 with HPV DNA improved the accuracy in distinguishing between CIN3 and

Age related influence on screening coverage and satisfaction. with CervicalCheck.

The aim of this study was to evaluate levels of satisfaction of women attending the CervicalCheck programme and reasons for the age differential in screening uptake. A questionnaire was sent to 5,000 randomly selected attenders with a normal smear test (3,500 aged 25-44, 1,500 aged 45-60). Almost all in both age groups said they would return to CervicalCheck if invited (98.5%; 98.5%) and recommend the service to family/friend (99.6%; 99.5%). The single independent predictor of 'would recommend to family/friend' was willingness to return to CervicalCheck (OR = 31 (5.2-183.7)). Predictors of 'would return if invited' were knowledge of when due to return (OR = 2.5 (1.3-5.0)) and having contacted or having received a letter of invitation from CervicalCheck (OR = 3.1 (1.6-6.1)). Independent predictors of 'knowledge of when due to return' were older age group (OR = 0.5 (0.4-0.7)) and willingness to return to CervicalCheck (OR = 3.2 (1.2-6.3)). The GP is particularly important in informing older women and encouraging attendance.

Apparent improvement in survival for carcinoma of the cervix following the introduction of chemoradiation--a Will Rogers phenomenon.

The improved survival for bulky cervical cancers (> 4cm) reported with combination platinum based chemoradiation (1999) prompted a move away from surgery as these cases frequently received adjuvant radiotherapy and were exposed to the morbidity of multimodality treatment. The period pre-1999 (Group 1) was compared with post-1999 (Group 2) when chemoradiation was the preferred treatment for bulky operable cervical cancer. Significantly more cases were treated surgically among Group 1 compared with Group 2 (79% vs. 62%; P < 0.001). Switching from surgery to radiotherapy improved survival in both treatment categories (73% vs. 78% and 37% vs. 44%, respectively) but with no improvement in overall survival (70%/ov.s 70%). Survival (86%) was similar in both groups among surgically treated women with tumors < 4 cm, but significantly more in Group 2 with negative nodes received postoperative adjuvant chemoradiotherapy (Groups 1 vs. 2; 16% vs.37.5%: P < 0.001) and overall the surgically treated patients received more not less multimodality treatment (46.5% vs. 59%; P = 0.7).

Diagnostic and therapeutic dilemma associated with atypical glandular cells on liquid-based cervical cytology.

BACKGROUND: In 2008, the management of women in Ireland with atypical glandular cells changed to immediate referral to colposcopy. The optimal management of these women is unclear. A balance between the detection of occult disease and overtreatment is required. METHODS: Our study aim was to document the experience of this policy at the National Maternity Hospital, Dublin. Information from the computerized data management system was analysed with the statistical package SPSS. RESULTS: In 2009, 156 women attended colposcopy following a single atypical glandular cell diagnosis on liquid-based cytology. The mean age was 41 years. Thirty (19.2%) women had abnormal vaginal bleeding, 31 (19.9%) were smokers and 34 (21.8%) had received previous treatment. The colposcopy was satisfactory in 125 (80.1%) and unsatisfactory in 31 (19.9%). Cervical histology was available for 146 (93.6%) women: 57 excisional procedures and 89 diagnostic biopsies. Abnormal histology was detected in 46 women (31.5%). Four women (2.7%) had invasive cancer, five (3.4%) had adenocarcinoma in situ, 21 (14.4%) had cervical intraepithelial neoplasia (CIN) grade 2 or 3 and 16 (11.0%) had CIN1. No abnormality was detected in 100 women (68.5%), including 35 (61.4%) of those who had undergone excisional procedures. The colposcopic impression in this group was unsatisfactory in 10 women (28.6%), glandular abnormalities in six (17.1%), high- and low-grade changes in 12 (34.2%) and six (17.1%) women, respectively, and normal in one (2.9%). The findings were essentially negative in the remaining 10 women: overall, 30 (19.2%) of the 156 women referred to colposcopy had at least CIN2. CONCLUSION: This study confirmed significant levels of high-grade disease in women referred to colposcopy with atypical glandular cells on cytology. Concerns about undetected endocervical disease resulted in high levels of negative excisional biopsies. Alternative strategies, including endometrial sampling, human papillomavirus testing and discussion at clinicopathological meeting, should be considered.

Survival in women with ovarian cancer before and after the introduction of adjuvant paclitaxel; a 25-year, single institution review.

Adjuvant chemotherapy regime for ovarian cancer patients remains to be a contentious issue. The aim of this study was to compare the overall and progression-free survival of women with ovarian cancer before and after introduction of paclitaxel in our unit in 1992. A sample of 112 women who received adjuvant therapy following surgery for ovarian cancer was collected, 68 (61%) received platinum+alkylating agent before 1992 and later 44 (39%) received platinum+paclitaxel. Five-year survival was same in both treatment groups when there was no macroscopic disease after surgery (78% versus 70%) and when residual disease was <2 cm (50% versus 40%). Survival was greater in women with residual disease >2 cm in the platinum+paclitaxel group (50% versus 24%), (p = 0.04). However, progression-free survival was similar in both groups irrespective of stage or residual volume of disease. Therefore consideration to selective use of paclitaxel could reduce patient morbidity and costs significantly.

Lymphovascular space involvement in early stage well-differentiated endometrial cancer is associated with increased mortality.

OBJECTIVE: To study the relationship between lymphovascular space involvement (LVSI) in stage 1a or 1b well-differentiated endometrial cancer and survival. DESIGN: Retrospective study consisting of a search of an oncology database to identify women with endometrial cancer between January 1990 and December 2004. SETTING: Tertiary referral centre, Dublin, Ireland. SAMPLE: Women who had well-differentiated stage 1a or 1b endometrial cancer. METHODS: During the period 1990-2004, 226 patients with endometrial cancer were treated in the National Maternity Hospital, Dublin. We looked at all patients who had well-differentiated endometrioid adenocarcinoma of the endometrium with invasion of <50% thickness of the myometrium. Forty-one patients fulfilled these inclusion criteria. The presence or absence of LSVI was determined by review of haematoxylin and eosin sections. Patients were followed for 5 years or till death if earlier. Mortality was calculated. Statistical analysis was performed using Fisher's exact test. An odds ratio and 95% confidence interval was calculated using fixed effect Mantel-Haenszel model. MAIN OUTCOME MEASURES: Death from recurrence of endometrial cancer. RESULTS: Of the 41 patients, five (12%) were found to have (LVSI). Of the five patients with LVSI, three (60%) patients died of recurrence. All patients with recurrence died of disease and none of the patients without LVSI died (0 of 36). Overall, the survival rate was 92.7%. The presence of LVSI was a highly significant predictor of recurrence (P < 0.001). CONCLUSION: In patients with early stage well-differentiated adenocarcinoma of the endometrium, the presence of LVSI is associated with a high risk of death.

Management of minor cervical cytological abnormalities: a systematic review and a meta-analysis of the literature.

BACKGROUND: A significant number of women are diagnosed with a low grade cytological abnormality on cervical screening. Many authorities recommend surveillance as spontaneous regression might occur. However, protracted attendance for cytological follow-up decreases with time and might put some women at risk of developing invasive disease. The aim of this review was to assess management options for women with minor cervical disease. METHODS: An electronic literature search was conducted. All randomised controlled studies comparing immediate colposcopy to cytological surveillance in women with cervical atypia/borderline nuclear changes or low-grade lesions were included. The main outcomes studied were the default rates from the colposcopy clinic and the histological status of biopsies within immediate management protocols compared to biopsies taken on completion of surveillance. Pooled relative risks and 95% confidence intervals were calculated using a random-effect model and inter-study heterogeneity was assessed with Cochrane's Q-test. RESULTS: Three randomised controlled trials identified from the literature search with different surveillance periods were combined. The analysis revealed that compliance with follow-up declines over time and reaches significance at the end of 24 months of surveillance (RR: 74.10 [10.36, 529.79]). There was a significantly higher incidence of HPV and CIN 1 in those women referred to immediate colposcopy/treatment compared to those at the end of 24 months surveillance period (32% vs 21%) (RR 1.49, 95% CI 1.17-1.90) and (21% vs 8%) (RR 2.58, 95% CI 1.69-3.94), respectively, possibly explained by spontaneous regression of clinically non-important lesions. Finally, there was no significant difference in the incidence of CIN2 or worse at initial colposcopy compared with the observation group (24 months) (RR 1.72, 95% CI 0.85-3.48). CONCLUSION: Cytological surveillance puts women at risk as many show poor compliance and such women might have occult high grade abnormalities. A general policy should be immediate colposcopy for all women after a single low grade cervical smear.

Early stage endometrial carcinoma--a study of management and outcome.

The surgical management of early stage endometrial carcinoma is controversial. The benefits of pelvic lymphadenectomy and administration of radiotherapy in this group have been disputed. We aimed to document the experience of stage 1 endometrial carcinoma at the National Maternity Hospital during the 10 year period 1989-1998 and to evaluate and compare clinical outcomes between retrospectively-assigned low and high-risk tumour groups. Seventy seven women were diagnosed with Stage 1 endometrial carcinoma in this period. Thirty-nine women had low-risk and 38 had high-risk tumours. Women with high-risk tumours were older and had a higher rate of lymph-vascular space invasion by tumour on histological examination. Three women (3.9%) developed disease recurrence and died of their disease; one low-risk and two high-risk tumour patients. Survival without recurrence did not differ between the two risk groups. No consistent pattern existed in surgical staging between the two risk groups. A prospectively-assigned definition of risk would minimise variations in clinical practice by providing a basis for a more tailored approach to adjuvant treatments.

Cervical screening history in patients with early stage carcinoma of the cervix.

This study aimed to examine whether a decade of heightened publicity on issues relating to cervical screening has changed the screening profile of women presenting with cervical cancer at the National Maternity Hospital. The screening history of 100 women diagnosed with early/surgically treated cervical cancer between 1998 and 2002 was compared with a similar study conducted in 1982 /1990. The percentage of women never screened was similar - 24 %( 2002) and 23% (1990). The interval between last recorded smear and diagnosis of disease was greater than 5 years in 45.6% and 41.7% respectively. Overall 60% of women in the recent period had either failed to avail of screening or were not screened within 5 years of diagnosis compared with 64% in 1990. Multiparous women comprised 90% of the study group and 50% of those inadequately screened were attending their general practitioner on a regular basis - therefore affording a potential for opportunistic screening The current method of screening has failed in this group and has not improved in 10 years despite of increased population awareness and greater opportunities for screening than ever before and would support an argument for a National Screening Program.

Prevalence of Epstein-Barr virus in the cervix.

Cervical smears from 327 women were examined using the polymerase chain reaction (PCR) targeted to a sequence in the Bam H1 W region of the Epstein-Barr virus (EBV) to determine the prevalence of the virus in the cervix. EBV was detected in 131 (40%) of the 327 women. Of the 235 women with normal cytology, 98 (42%) were positive. Of the 92 women with dyskariotic smears, 33 (36%) were positive.

En bloc radical vulvectomy and lymphadenectomy with modifications of separate groin incisions.

A new modification of radical vulvectomy and lymphadenectomy through separate groin incisions involves dissection of the intervening skin bridge and allows an en bloc dissection. The results in 26 women treated with this technique are compared with those of seven treated with separate incisions without an en bloc dissection. All 33 women had squamous carcinoma of the vulva and were treated between 1985-1989. The incidence of advanced disease was high, with nodal metastases present in 52% of cases. Dissection of the tissue beneath the skin bridge did not alter the morbidity of the procedure in terms of the incidence of wound infection, number of units of blood transfused, or duration of hospitalization. The only case of an isolated recurrence in the skin bridge occurred in a woman who did not have an en bloc dissection, although there was no significant difference in the overall local recurrence rate between the groups. Further evaluation with larger numbers is required, but we suggest that an en bloc dissection using separate incisions may reduce the risk of isolated recurrence in the skin bridge, particularly in patients with advanced disease.

Prognostic factors in surgically treated stage IB-IIB carcinoma of the cervix with negative lymph nodes.

Comerci G, Bolger BS, Flannelly G, Maini M, de Barros Lopes A, Monaghan JM. Prognostic factors in surgically treated stage IB-IIB carcinoma of the cervix with negative lymph nodes. Int J Gynecol Cancer 1998; 8: 23-26. Two hundred and seventy-five females with stage IB-IIB negative lymph node cervical cancer, treated between January 1988 and December 1994 by radical hysterectomy and pelvic lymph node dissection, form the basis of this analysis. The clinical records were reviewed for all patients including histopathology, clinical features at presentation, and follow-up. Tumors were re-staged according to the 1995 FIGO classification. Median follow-up was 55 months and 85.8% were followed for longer than two years. There were 21 recurrences, 12 of which were true central recurrence (disease-free survival at 5 years: 91.66%). Fifteen of 25 deaths were due to cervical cancer (crude survival at 5 years: 93.27%). In univariate log-rank analysis, stage (P = 0.005), tumor size (P = 0.0002), and lymph-vascular space involvement (LVSI) (P = 0.01) appeared to be statistically significant factors for tumor recurrence. Other factors including age, histology type, differentiation, adjacent cervical intraepithelial neoplasia or cervical glandular intraepithelial neoplasia, and presence of intraepithelial disease at resection margin were not found to be statistically significant. In multivariate analysis (Cox regression) tumor size (P = 0.02) and LVSI (P = 0.03) were the only independent variables. In the presence of negative lymph nodes and complete surgical excision, tumor size and LVSI are important predictors of local recurrence.

Outpatient loop diathermy conization as an alternative to inpatient knife conization of the cervix.

A knife cone biopsy of the cervix is usually performed as an inpatient procedure under general anesthesia and is associated with significant morbidity. Loop diathermy conization was performed under local anesthesia on colposcopy outpatients as an alternative to knife conization. In 33 consecutive patients studied the procedure was well tolerated, there were no operative complications, and a satisfactory specimen for histologic examination was obtained in every case. One case of unsuspected invasive cancer and two of suspected microinvasive cancer were diagnosed. The diagnosis of cervical precancer was made in 24 (73%) of the cases. The introduction of outpatient loop diathermy conization of the cervix instead of knife conization would decrease hospitalization costs, avoid the need for general anesthesia and potentially reduce short-term patient morbidity.

Persistent hyperemesis gravidarum complicated by Wernicke's encephalopathy.

Wernicke's encephalopathy is a serious neurological manifestation of vitamin B1 deficiency. We report a case occurring secondary to hyperemesis gravidarum.

A clinical review of cervicography.

A new investigative modality, cervicography, has been advocated for cervical screening. In the first 51 patients referred for colposcopy because of an abnormal cervicogram, none had invasive cancer and 75% had preinvasive cancer. The cervicogram appears superior to cytology but inferior to colposcopy in the detection of cervical pathology. Based on the available evidence, however, cervicography cannot be recommended for universal screening. It may have a role in the follow-up of patients with a mildly abnormal cervical smear, but the optimum management remains early referral for colposcopy.

Management of women with mild and moderate cervical dyskaryosis.

OBJECTIVE: To compare the outcomes in women with mild and moderate dyskaryosis after increasing periods of surveillance and thereby to define a rational protocol for managing such women. DESIGN: Prospective study with randomisation of women to one of four treatment groups, each with a different period of surveillance; one group in which the women were given immediate treatment and three other groups in which the women were under surveillance for six, 12, and 24 months. SETTING: A dedicated colposcopy clinic in Aberdeen, Scotland. SUBJECTS: 902 women who presented with a mildly or moderately dyskaryotic smear for the first time. INTERVENTIONS: Cytological and colposcopic examinations at intervals of six months until the allocated period of surveillance was completed, at which time biopsy was performed. Women with severe dyskaryosis were withdrawn from surveillance and a biopsy was performed. MAIN OUTCOME MEASURES: The histological findings after punch biopsy or large loop excision of the transformation zone, and the trends in cytological appearances of serial cervical smears. RESULTS: 793 women completed the study. In all, 769 women had an adequate final smear, of which 197 were normal cytologically, 328 were still mildly or moderately dyskaryotic, and 244 were severely dyskaryotic. Seventeen of the 67 (25%) women with one repeat smear showing non-dyskaryosis had cervical intraepithelial neoplasia grade III compared with only one of the 31 (3%) women with no dyskaryosis in four repeat cervical smears (P < 0.0001). None of the women had invasive cancer. Of 158 women whose index smear showed mild dyskaryosis and who were allocated to the group under surveillance for two years, only 40 had not defaulted or still had dyskaryotic smears by the end of the two years. CONCLUSION: Cytological surveillance, although safe, is not an efficient strategy for managing women with mildly abnormal smears. Women with any degree of dyskaryosis in a smear should be referred for colposcopy.

Mild and moderate dyskaryosis: can women be selected for colposcopy on the basis of social criteria?

OBJECTIVE: To describe the distribution of cervical intraepithelial neoplasia grades among women with mild and moderate dyskaryosis after a single cervical smear and to determine whether social criteria could help identify women who are at increased risk of grade II or III disease. DESIGN: Cross sectional analysis within a randomised prospective study. Subjects had a repeat smear, a colposcopic examination, and an excision biopsy of the transformation zone. In addition, women were asked to complete a social questionnaire. SETTING: Colposcopy clinic, Aberdeen. SUBJECTS: 228 women with a single smear test showing mild or moderate dyskaryosis. MAIN OUTCOME MEASURES: Histology, age, sexual and contraceptive history, cigarette smoking. RESULTS: 159 (70%) women had cervical intraepithelial neoplasia grades II or III. Among current smokers the prevalence of grade II and III disease was higher in women who smoked greater than or equal to 20 cigarettes a day (84%) than among those who smoked less (66%; p less than 0.04). Women with more than one sexual partner also had a higher prevalence (75%) than women with only one partner (50%; p = 0.0028). Use of oral contraceptives and younger age were not significantly associated. The prevalence of grade II or III disease was up to 66% in the lower risk groups. CONCLUSIONS: Because of the high prevalence of cervical intraepithelial neoplasia grades II and III in both the high and the low risk groups social factors are not useful for selecting women with mild or moderate dyskaryosis for either early referral to colposcopy or cytological surveillance.

Cytological screening history of patients with early invasive cervical cancer.

The value of population screening for cervical cancer has recently been questioned. The purpose of this study was to examine the cytological screening history in 100 consecutive patients undergoing Wertheim's hysterectomy for early invasive cervical cancer. Twenty three per cent of the patients were never screened; the screening history was unavailable in 11%; the patient was referred appropriately in 21%; there was a delay in referral for gynaecological assessment in 21%; the patient's previous cervical smear before referral was normal in 24%. If population screening in Ireland is to have an impact on mortality from cervical cancer, the results of this study indicate that greater attention needs to be given not only to extending the number of women screened, but also to increasing the frequency of screening and to improving the clinical response to an abnormal smear.