Factors associated with failed 'test of cure' in the NHS Cervical Screening Programme: A retrospective cohort study.

OBJECTIVE: To determine predictive factors associated with failed 'test of cure' (TOC) in the NHS Cervical Screening Programme (NHSCSP). METHODS: Retrospective cohort study of all patients treated by large loop excision of transformation zone (LLETZ) between 1st April 2014 and 1st April 2019. Those with no documented HPV genotype on referral, no TOC outcome, those having a hysterectomy, chemotherapy and/or radiotherapy were excluded from final analysis. RESULTS: Patients referred with a singular HPV genotype of HPV 16, HPV 18, or HPV Other types (HPV O) were significantly more likely to pass TOC than those referred with multiple HPV genotypes (p < 0.0001). Those with HPV genotypes including HPV O were significantly more likely to fail TOC as compared to those with genotypes of solely HPV 16 and/or 18 (p < 0.0001). Patients aged ≥51 years were significantly more likely to fail TOC when compared to all other age groups (p < 0.0001). CONCLUSION: Age >51 yrs. and infection with multiple hr-HPV types were predictors of post treatment hr-HPV persistence. Knowledge of HPV genotype both at referral, and following treatment, could allow a more individualised, and patient-centred, approach to both the management and follow up of CIN. HPV genotype should be reported as standard on all cervical screening sample results. The term HPV O should not be utilised and instead actual HPV genotype should be reported. This would enable us to optimise not only future research but would also allow future monitoring of the efficacy of vaccination programmes.

Invasive cervical cancer audit: What lessons can we learn locally and where would we stand with regard to duty of candour?

OBJECTIVE: To identify lessons learned locally from the invasive cervical cancer audit. To estimate the impact that the application of 'Duty of Candour' may have upon our future service provision. METHODS: Retrospective cohort study with interval analysis of all women diagnosed with cervical cancer at Sheffield Teaching Hospitals NHS Foundation Trust between 1 April 2007 to 31 December 2019. Data were collected prospectively with retrospective categorisation by screening history and invasive cervical cancer audit outcomes as satisfactory, satisfactory with learning points, and unsatisfactory. Statistical analysis was performed using the chi-squared test and paired t-test. RESULTS: Cervical cancer was diagnosed in 344 women. Seventy-eight (23%) had no record of prior cervical cytology, 108 (31%) had delayed attendance to the screening programme, 102 (30%) were detected by routine screening, and 56 (16%) were screening programme compliant. Satisfactory management was undertaken in 301 (87.5%) cases, 26 cases (7.5%) were satisfactory with learning points, and 17 cases (5%) were considered as unsatisfactory. CONCLUSIONS: Seventeen cases were applicable to the Duty of Candour process equating to 1.3 cases per year, incurring minimal impact upon future service provision. Invasive audit categorisation is subject to bias, however, with the potential for considerable intra- and inter-observer variation; the authors accordingly recommend that a further study be conducted to investigate both the consistency and reproducibility of the invasive cervical cancer audit categorisation.

Clinical indications referrals - what is the risk of premalignant and malignant female genital tract disease in women referred to a dedicated nurse-led colposcopy service? A retrospective cohort study.

Post-coital bleeding (PCB) is a poor predictive factor for cancer and should not be managed as urgent referral. Urgent referral to colposcopy is justified however, in the presence of a visible suspicion of cervical cancer. This retrospective cohort study of women attending a clinical indications referral service aims to identify the risk of pre-malignant and malignant disease in women with clinical indication referrals to colposcopy. Thirty-seven of 3521 women (1%) were diagnosed with pre-malignant cervical or endometrial disease; 14 women (0.4%) were diagnosed with cancer (11 cervix, three endometrial). To detect one cancer in women referred with an abnormal cervix, one would need to see 70 women; to detect one cancer in women referred with PCB one would need to see 790 women. Improved education in primary care and obstetrics and gynaecology training is key to improving clinical indications referral services, which is otherwise an effective and efficient service.Impact StatementWhat is already known on this subject? Post-coital bleeding is a poor predictive factor for cancer and should not be considered an urgent referral.What do the results of this study add? The presence of a visible suspicion of cervical cancer however does warrant urgent referral as approximately one in 70 women will have a malignancy detected.What are the implications of these findings for clinical practice and/or further research? Improved education in primary care and obstetrics and gynaecology training is the key to improving clinical indications referral services.

Are we managing our patients correctly following treatment for cervical glandular intraepithelial neoplasia? A review of practice at the Jessop Wing Colposcopy Unit.

OBJECTIVE: Women diagnosed with cervical glandular intraepithelial neoplasia (CGIN) remain at risk of further pre-malignant and malignant disease and require rigorous post-treatment follow-up. We assess the effectiveness and safety of community cervical sampling follow-up in women treated for CGIN. METHODS: A retrospective study was conducted of women diagnosed with CGIN between April 1, 2013, and March 31, 2019, at Jessop Wing Colposcopy Unit, Sheffield, UK. RESULTS: Of 140 women diagnosed with CGIN, 76 had co-existing cervical intraepithelial neoplasia (CIN). Cytologists were significantly more likely to report glandular neoplasia in the absence of co-existing CIN, and high-grade dyskaryosis in its presence (Ps < 0.0001). Co-existing CIN was significantly more likely to be present with high or low-grade compared to normal colposcopy findings (P < 0.0001). The 6-month test of cure (TOC) was attended by 67% of women (84% within 12 months), and the 18-month post-treatment sampling by 52.5% of women (70% within 24 months). Colposcopy recalled 96% of women correctly for the 18-month sampling, but 20% of women undertaking primary care samples were incorrectly recalled at 3 years instead. CONCLUSIONS: When CGIN is diagnosed, two dates for recall should be provided at 6 and 18 months post-treatment to the Cervical Screening Administration Service and the centralised screening laboratory ensuring the 18-month post-treatment sample is correctly appointed, preventing women with HPV-negative TOC samples being returned to 3-year recall. Follow-up of CGIN should be closely audited by the centralised laboratories ensuring women with CGIN are not put at additional risk.

Can We Be Less Radical with Surgery for Early Cervical Cancer?

Although a rare cancer in the developed world due to the success of cervical screening programmes, cervical cancer remains one of the most common cancers diagnosed in women under the age of 35 years old. Radical hysterectomy and more recently radical trachelectomy have been highly effective in curing the majority of women with early stage disease. Many, however, are left with long-term 'survivorship' issues including bowel, bladder and sexual dysfunction. In view of these chronic co-morbidities, many clinicians now consider whether a less radical approach to surgery may be an option for some women. This review focuses on the current evidence for the safety of conservative surgery for early stage cervical cancer with regard to cure rates in comparison to standard management, as well as any improvement in short and long-term morbidity associated with a more conservative approach.

Management and Outcomes of Patients with Stage I and IlIl Low-Risk Gestational Trophoblastic Neoplasia Treated in Sheffield, UK, from 1997-2006.

OBJECTIVE: To review the outcome of patients treated for low-risk gestational trophoblastic neoplasia (GTN) over a 10-year period with the particular aim of assessing response to treatment in Stages I and III disease. Approximately 90% of women requiring treatment for GTN have low-risk disease. Methotrexate is the treat- ment of choice in the UK and achieves complete response rates of 50% and 90%. STUDY DESIGN: A retro- spective review of management and outcomes of patients treated for low-risk GTN at the Trophoblastic Disease Centre, Sheffield, UK, from 1997 to 2006. RESULTS: Overall 280 patients were treated for low- risk GTN during this time; 8.6% had stage III disease. Single-agent methotrexate was used as first-line therapy in 99% of cases, with a remission rate of 56%. There was no significant difference (p=0.67) in the complete response rate after first-line methotrexate between those with stage I and those with stage III disease. CONCLUSION: The overall cure rate for women with low-risk GTN was high (99.6%), and the complete response rate after first-line management was not sig- nificantly different between stages I and III disease.

Endometrial cancer rate in Hormone replacement therapy users with postmenopausal bleeding: Retrospective cohort study.

OBJECTIVE: To establish the endometrial cancer detection rate in women using hormone replacement therapy presenting with postmenopausal bleeding. STUDY DESIGN: Retrospective cohort study. Setting and populationRapid access gynaecology clinic at a tertiary hospital. Women aged under 60 years referred with postmenopausal bleeding. METHODS: Retrospective study of referrals received between 1 January 2019 and 31 December 2020 including Hormone replacement therapy (HRT) use and histological diagnosis. MAIN OUTCOME MEASURES: Histological diagnosis of endometrial cancer, borderline ovarian tumour or endometrial intraepithelial neoplasia. STATISTICAL ANALYSIS: Chi squared test. RESULTS: 1363 women were included. 214 women were using HRT when they experienced PMB and only one of these had endometrial cancer at histology (cancer detection rate 0.47%). 25 of the 1124 women who were not using HRT were diagnosed with endometrial cancer on histology (cancer detection rate 2.18%). Chi squared statistical analysis confirmed this was statistically significant (p value .0156). CONCLUSIONS: The endometrial cancer detection rate in women aged under 60 years using HRT with PMB is very low. Referral on a two-week wait pathway for suspected cancer diagnosis induces stress and anxiety for the woman and may lead to more invasive initial investigation even though other diagnoses are far more likely. Women aged under 60 years with postmenopausal bleeding that have either commenced HRT or had a change to their preparation within the last 6 months should be seen on a less urgent referral pathway if necessary given the very low probability of endometrial cancer.

Stage of ovarian cancer at diagnosis. Does presentation as an emergency make a difference?

OBJECTIVES: The purpose of this study is to evaluate whether presentation of ovarian cancer as an emergency compared to presentation via referral to diagnostic clinic has an impact on stage of disease at diagnosis. Secondary outcomes include the relationship between stage of diagnosis and age as well as socioeconomic status and type of presentation (emergency or clinic referral). STUDY DESIGN: Data were obtained from the central database for all new diagnoses of ovarian, fallopian tube or primary peritoneal malignancy at a tertiary teaching hospital for 2016-2018 (n = 147). The electronic patient records were manually reviewed to determine the patient's presentation. Age and stage at diagnosis were from the central records. Socioeconomic status was determined by the multiple deprivation index deciles obtained from patient postcode data. Non parametric chi squared analysis was used to assess for any significant results. RESULTS: 51 % of women presented through a gynaecology two-week wait service; 27 % presented as an emergency admission; 12 % through a routine gynaecology outpatient clinic and 10 % after initial referral to a non-gynaecological two-week wait service. There was a significant (p = 0.008) association with later stage disease and emergency presentation. Increased age was also strongly linked to later stage at diagnosis (p = 0.00001). There was no association between stage at diagnosis and socioeconomic status. CONCLUSIONS: Emergency presentations account for just over a quarter of new diagnoses and are significantly associated with later stage disease with increased morbidity and mortality. Older women were also more likely to present at an advanced stage. Socioeconomic status did not impact on staging at diagnosis.

Choriocarcinoma after a nonterm pregnancy.

OBJECTIVE: To evaluate the characteristics and outcomes of patients with choriocarcinoma following a nonterm pregnancy and compare them to the results from the same unit of patients with choriocarcinoma following a term delivery. STUDY DESIGN: A retrospective case review of all patients with choriocarcinoma after a nonterm pregnancy referred to the Trophoblastic Screening and Treatment Centre, Sheffield, between 1976 and 2008. RESULTS: Sixty-four patients were referred after a nonterm pregnancy. Time to diagnosis was longer in the nonterm pregnancy patients compared to patients referred following a term pregnancy. Mean human chorionic gonadotrophin (hCG) level, however, was lower in the nonterm pregnancy group: 91,329 IU/L vs. 192,121 IU/L for the term pregnancy group. The number of patients with metastases at presentation was similar in both groups (57% following term pregnancy, 51% following nonterm pregnancy), although more of the nonterm pregnancy patients received methotrexate therapy only: 36% vs. 23%. Survival in both groups was > 90%. CONCLUSION: The presence of metastases, excluding pulmonary, had an adverse effect on outcome in both groups and, in accord with published data, that site and number of metastases have more impact on outcome than type of antecedent pregnancy.

Influence of high risk HPV genotype on colposcopic performance: A large prospective study demonstrates improved detection of disease with ZedScan I, particularly in non-HPV 16 patients.

OBJECTIVE: To assess the influence of high-risk Human Papilloma Virus (hrHPV) genotyping on the detection of high-grade disease (CIN2+) using colposcopic impression both with and without electrical impedance spectroscopy (ZedScan I) as an adjunct. STUDY DESIGN: A prospective cohort of women with a known hrHPV genotype referred to a single colposcopy service. RESULTS: 839 women underwent colposcopy and ZedScan I examination. 613 women were referred with abnormal cytology; 411 (67%) with low-grade dyskaryosis (67%) and 202 (33%) with high-grade dyskaryosis. 187 were referred with persistent hrHPV but negative cytology. 35 were attended for follow up and 4 for a clinical indication. 159 (19%) women were positive for HPV16 only; 54 (6%) with HPV18 only, 443 (53%) women were positive for hrHPV other types (HPV O). 183 (22%) were positive for multiple hrHPV genotypes. CIN2+ was present in 170 (84.2%) of high-grade and 69 (16.7%) of low-grade cytology referrals. Colposcopy was better at detecting HPV16 associated CIN2+ than that associated with HPV18 or HPV O (86.9% vs 79.7%, p=0.0191). ZedScan I increased the detection of CIN2+ from 85.6% to 96% irrespective of hrHPV genotype status (p<0.0001). CONCLUSION: The use of an electrical impedance spectroscopic device (ZedScan I) increases detection of CIN2+ irrespective of hrHPV genotype.