None listed
Conditions
Brief summary
In 2018, the NZ cervical screening age will increase from 20 to 25 years. This will lead to a delay in the diagnosis and treatment of high grade cervical abnormalities in young women of up to 5 years. Cervical cancer is rare in young women and cervical screening in women aged 20-24 has been shown to have little to no impact on rates of invasive cervical cancer up to age 30. Despite this, currently, ~1100 NZ women aged 20-24 years are diagnosed with high grade cervical cell abnormalities (CIN2 and 3) each year. Usually these women are treated and we have a poor understanding of the impact of deferred diagnosis on these lesions. However, there is growing evidence that a high proportion of CIN2 lesions naturally resolve in young women. In contrast, data regarding CIN3 regression rates are lacking and the impact of delayed CIN3 diagnosis and treatment in young women is poorly understood. The primary aims of the pilot study are to document over 12 months, for a cohort of n=50 women under the age of 25 with a diagnosis of CIN3; safety of delayed identification and treatment of CIN3 in young women, recruitment rate, and to give an indication of CIN3 regression rates. Women <25 years with biopsy-diagnosed CIN3 (including CIN2/3) will be identified in large colposcopy centres in NZ and invited to participate. Pathology and cytology specimens will be reviewed at a multidisciplinary meeting. Provided they meet eligibility criteria, consenting women will undergo observational management (i.e., repeat colposcopy, cytology, and cervical biopsy performed every 6 months for up to 12 months). Treatment is indicated if the patient becomes symptomatic, there is suspicion of invasive or glandular disease, the patient requests treatment, the patient completes 12 months follow-up or at their first follow-up after their 25th birthday (whichever is sooner) without demonstrating persistent regression. Regression is defined as two consecutive colposcopy follow-ups showing CIN1 or less. The trial will be terminated prematurely if; invasive carcinoma of the cervix (>1a) is diagnosed in any study participant; or microinvasive squamous carcinomas are diagnosed >2% of study participants. Primary outcome measures: Proportion of participants 1) whose lesions regress to CIN1 or less, 2) who progress to invasion, 3) who require treatment, and 4) who are lost to follow up. We hypothesise that CIN3 observational management can be safely performed for women aged less than 25 years and that within this hypothesis, we estimate that no women will develop >1a carcinoma, <5% of participants will be lost to follow up and the recruitment rate will be at least 40% of eligible participants.
Interventions
Observational management of Cervical Intraepthelial Neoplasia (CIN) grade 3 in women aged under 25 years for 12 months i.e., 6-monthly colposcopy examination with a directed cervical biopsy (histology), and cervical smear (cytology) undertaken by a trained colposcopist at a hospital-based colposcopy clinic for a total of 1 year (or until the woman turns 25 years old, whichever is sooner).
Attention will be paid to ensure the whole transformation zone and lesion are seen and that there is no col
Observational management of Cervical Intraepthelial Neoplasia (CIN) grade 3 in women aged under 25 years for 12 months i.e., 6-monthly colposcopy examination with a directed cervical biopsy (histology), and cervical smear (cytology) undertaken by a trained colposcopist at a hospital-based colposcopy clinic for a total of 1 year (or until the woman turns 25 years old, whichever is sooner). Attention will be paid to ensure the whole transformation zone and lesion are seen and that there is no colposcopic evidence of glandular or invasive disease. If a lesion persists, representative biopsies must be taken, two if possible and one from each quadrant in larger lesions. If the colposcopy is normal, we encourage the taking of a biopsy from the transformation zone in the previously affected area. Treatment is indicated if the patient becomes symptomatic, there is colposcopic or cytological suspicion of invasive or glandular disease, the colposcopy is unsatisfactory and abnormal cytology persists, the histology is reported as invasive or glandular disease, the patient requests treatment, turns 25 years old without demonstrating persistent regression, or is unable to attend further follow up and the lesion persists. If treatment is performed a trial Completion Form is filled in and the patient subsequently managed as per normal practice. If CIN2 or 3 persists, or cytology is reported as ASCH or HSIL, colposcopy should be repeated at 6 monthly intervals for 1 year. If CIN2 or 3, or ASCH or HSIL cytology persists, at this point, the patient should be treated. At this point, a trial Completion form is filled in. Regression is: - normal colposcopy, normal/low grade cytology, no biopsy taken OR - normal colposcopy, normal/low grade cytology, normal/low grade histology OR - low grade colposcopy, normal/low grade cytology, normal/low grade histology OR - CIN 2 colposcopy but normal/low grade cytology, normal/low grade histology Regression is not confirmed: - CIN 3 colposcopy but normal/low grade cytology, normal/low grade histology - if a lesion is present and a biopsy not taken - if cytology is ASCH or worse or - a smear is not taken or unsatisfactory If regression is documented women must have a follow-up at 6 months with; - a repeat colposcopy and smear and - a biopsy if a lesion is present If following the repeat colposcopy, criteria for regression is again met, the lesion has demonstrated persistent regression. Following persistent regression and after discussion between the colposcopist and the woman, the patient may be discharged from the colposcopy clinic. If this is the case, a trial Completion Form is filled and follow-up is then as per National Cervical Screening Programme (NCSP) guidelines following high grade abnormality with a smear in 6 months (by primary smear taker). If the woman is not discharged from colposcopy clinic, a repeat colposcopy occurs at 6-12 months. Management should be based on the NCSP guidelines. If regression is demonstrated at the 12 month follow up for the first time, the colposcopist will discuss either immediate treatment or follow up at 6 months. However at this point, a trial Completion form will be filled in, and the patient subsequent management should be based on the results of this colposcopy and the NCSP guidelines. If following apparent regression, at the next follow up CIN2 or worse is seen or cytology is reported as ASCH or worse, 6 monthly follow up must continue unless the woman elects to be treated or continues on the trial protocol.
Sponsors
University of Otago, Christchurch
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
15 Years to 24 Years
Healthy volunteers
No
Inclusion criteria
- Age under 25 at date of initial biopsy. - Attending colposcopy clinic as a result of an abnormal smear but without a history of prior high grade abnormality. - Biopsy proven CIN3 (or CIN2/3). - Entire lesion accessible to colposcopy. - Participants in trial agree to six monthly colposcopy and cervical smear and biopsy for a total of two years. - Cytology and pathology reviewed and CIN3 confirmed at a multidisciplinary meeting and no other clinical factor was identified that would exclude them from the trial. - Signed informed consent
Exclusion criteria
- High grade cytological or histological abnormality prior to this referral. - Unsatisfactory colposcopy. - Large complex colposcopic abnormality where adequate histological sampling difficult. - Cytology suspicious of invasion or glandular abnormality. - Patients unwilling or unable to attend follow up. - Patients whose cytology and histology have not been reviewed at MDM. - Clinical suspicion of invasion or AIS. - Any glandular histological or cytological abnormality. - Concern on behalf of treating doctor that patient is unlikely to attend follow up. - Immunosuppression. - Pregnancy - Post-coital bleeding or any other irregular vaginal bleeding not attributable to oral contraceptive related break through bleeding
Outcome results
None listed