Clinical trial NCT03177863: Expectancy as Alternative to Treatment for Cervical Intraepithelial Neoplasia Grade 2 Among Women 25 - 30 Years of Age
Official title: Expectancy as Alternative to Treatment for Cervical Intraepithelial Neoplasia Grade 2 Among Women 25 - 30 Years of Age. A Multicenter Clinical Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: CIN2
Therapy
Keywords: neoplasm
uterine cervix
Lead sponsor: Sahlgrenska University Hospital
Sponsor class: OTHER
First posted: 2017-06-06
Enrollment: 125
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In the Swedish organised cervical screening program precursors of cervical cancer are detected and treated. Most precursor lesions detected by screening heal spontaneously. Those who progress do it slowly. There are three levels from light; CIN1, moderate; CIN2 to severe; CIN3. Women with CIN3 are always treated, regardless of age, according to current clinical guidelines. Women with CIN2 who are below the age of 25 years are offered active expectance for up to two years because there is good evidence that they will spontaneously heal their lesions (regression) in 40-70% of the cases during that time.

Method of treatment is today an excisional procedure of the cervix most often by Large loop excision of the transformation zone (LLETZ/LEEP) Treatment increases the risk of premature birth in a future pregnancy. In 2015 about 1800 excisional procedures of the transformation zone of the cervix were performed in the Västra Götalands regionen (VGR) om Sweden. The average age of first-time mothers in Sweden is rising and in 2014 it was 29 years. Postponed childbearing raises the question whether it is possible to refrain from surgery even for the group of women over 25 years old, with proven CIN2. Existing studies suggest that cure of CIN2 in the age group of and above 25 takes place in the same extent as under 25 years of age.There is lack of evidence concerning clinical follow-up.

In a prospective multicenter clinical cohort study (observational study) with careful monitoring, the investigators will examine what proportion of CIN2 changes regress spontaneously within two years in women, 25-30 years old, and if human papillomavirus (HPV) type 16 may can be a marker for poor regression in this group. Instead of LLETZ, active expectance is offered to women this age with CIN2 in five gynecological clinics in VGR. The study protocol includes gynecologist visits every 6 months for two years, including cytology, colposcopy and directed biopsies of the cervix. Power calculation shows 160 women needs to be included, which is expected to occur within one year from the start.

Detailed description: Available in Swedish

Eligibility criteria: Inclusion Criteria:

* CIN 2
* Written consent

Exclusion Criteria:

* CIN (any grade) not resolved
* Former treatment of CIN
* Immunomodulating medication
* Pregnancy (at start of study)

Primary outcomes:
measure: Proportion of regress
timeFrame: 24 months from date of visit when CIN2 was diagnosed
Secondary outcomes:
measure: Proportion of regress for women with HPV16
timeFrame: Proportion of women with CIN2 at inclusion who will regress to CIN1 or no evidence of disease
Other outcomes:
Locations:
city: Borås
country: Sweden
facility: Södra Älvsborgs Sjukhus
city: Göteborg
country: Sweden
facility: Kungshöjds gynekologmottagning
city: Göteborg
country: Sweden
facility: Frölunda specialistsjukhus
city: Skövde
country: Sweden
facility: Skaraborgs sjukhus, kvinnokliniken
city: Trollhättan
country: Sweden
facility: Norra Älvsborgs sjukhus, kvinnokliniken
Study officials:
affiliation: Sahlgrenska Academy, Gothenburg University, Sweden
name: Strander
role: PRINCIPAL_INVESTIGATOR
References:
citation: Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, Solomon D, Wentzensen N, Lawson HW; 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013 Apr;121(4):829-846. doi: 10.1097/AOG.0b013e3182883a34.
citation: Kyrgiou M, Mitra A, Arbyn M, Stasinou SM, Martin-Hirsch P, Bennett P, Paraskevaidis E. Fertility and early pregnancy outcomes after treatment for cervical intraepithelial neoplasia: systematic review and meta-analysis. BMJ. 2014 Oct 28;349:g6192. doi: 10.1136/bmj.g6192.
citation: Wilkinson TM, Sykes PH, Simcock B, Petrich S. Recurrence of high-grade cervical abnormalities following conservative management of cervical intraepithelial neoplasia grade 2. Am J Obstet Gynecol. 2015 Jun;212(6):769.e1-7. doi: 10.1016/j.ajog.2015.01.010. Epub 2015 Jan 9.
citation: Ostor AG. Natural history of cervical intraepithelial neoplasia: a critical review. Int J Gynecol Pathol. 1993 Apr;12(2):186-92.
citation: Discacciati MG, de Souza CA, d'Otavianno MG, Angelo-Andrade LA, Westin MC, Rabelo-Santos SH, Zeferino LC. Outcome of expectant management of cervical intraepithelial neoplasia grade 2 in women followed for 12 months. Eur J Obstet Gynecol Reprod Biol. 2011 Apr;155(2):204-8. doi: 10.1016/j.ejogrb.2010.12.002. Epub 2010 Dec 28.
citation: Guedes AC, Zeferino LC, Syrjanen KJ, Brenna SM. Short-term outcome of cervical intraepithelial neoplasia grade 2: considerations for management strategies and reproducibility of diagnosis. Anticancer Res. 2010 Jun;30(6):2319-23.
citation: Ho GY, Einstein MH, Romney SL, Kadish AS, Abadi M, Mikhail M, Basu J, Thysen B, Reimers L, Palan PR, Trim S, Soroudi N, Burk RD; Albert Einstein Cervix Dysplasia Clinical Consortium. Risk factors for persistent cervical intraepithelial neoplasia grades 1 and 2: managed by watchful waiting. J Low Genit Tract Dis. 2011 Oct;15(4):268-75. doi: 10.1097/LGT.0b013e3182216fef.
citation: Castle PE, Schiffman M, Wheeler CM, Solomon D. Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol. 2009 Jan;113(1):18-25. doi: 10.1097/AOG.0b013e31818f5008.