Follow-up Of Cervical Intraepithelial Neoplasia Research Articles

The 5-year risk of recurrence of grade 2/3 cervical intraepithelial neoplasia after treatment in a population screening programme by human papillomavirus status: A cohort study in central Italy.

(a) To estimate the risk of recurrent cervical intraepithelial neoplasia, grade 2/3 or worse (CIN2+/CIN3+), lesions within 5 years of follow-up in human papillomavirus-negative/human papillomavirus-positive cohorts; (b) to assess whether certain risk factors can predict the recurrence of CIN2+/CIN3+ lesions; and (c) to provide recommendations for follow-up after treatment of cervical intraepithelial neoplasia, grade 2/3 to prevent cervical cancer. Organized cervical cancer screening programme in Central Italy. We included 1063 consecutive first excisional treatments performed between 2006 and 2014 for screening-detected cervical intraepithelial neoplasia, grade 2/3 lesions among women aged 25-65. The study population was divided into two groups according to the human papillomavirus test results performed 6 months after treatment: Human papillomavirus-negative and human papillomavirus-positive cohorts. The 5-year risk of developing cervical intraepithelial neoplasia, grade 2/3 or worse (CIN2+/CIN3+) was estimated using the Kaplan-Meier method and the Cox regression model. Among 829 human papillomavirus-negative and 234 human papillomavirus-positive women, six (0.72%; three cervical intraepithelial neoplasia, grade 2, three cervical intraepithelial neoplasia, grade 3) and 45 (19.2%; 15 cervical intraepithelial neoplasia, grade 2, 30 cervical intraepithelial neoplasia, grade 3), respectively, developed CIN2+ recurrence within 5 years of follow-up. The cumulative risks for CIN2+ and CIN3+ were 0.9% (95% confidence interval: 0.4%-2.0%) and 0.5% (95% confidence interval: 0.1%-1.4%), respectively, for the human papillomavirus-negative cohort, and 24.8% (95% confidence interval: 18.5%-32.7%) and 16.9% (95% confidence interval: 11.4%-24.5%), respectively, for the human papillomavirus-positive cohort. Risk factors associated with increased risk of recurrence were both margins positive for the human papillomavirus-negative cohort, and positive margins, cervical intraepithelial neoplasia, grade 3 lesions, high-grade cytology and high viral load for the human papillomavirus-positive cohort. Human papillomavirus testing can identify women at increased risk of recurrence and this supports a recommendation for its use in the post-treatment follow-up of cervical intraepithelial neoplasia, grade 2/3 lesions.

Cytological Follow-Up of Cervical Intraepithelial Neoplasia 1 after Initial Management During 2-Year Period: Bhumibol Adulyadej Hospital Experience

Objective: To evaluate the frequency of cervical cytological results in patients diagnosed as low-grade squamous intraepithelial lesion (LSIL) in cytology report between women younger than 30 and woman 30 or older after initial management and the completed 2-year follow-up to suggest the proper management for Thai women. Materials and Methods: The present study was retrospectively conducted at Bhumibol Adulyadej Hospital, Bangkok, Thailand between January 2011 and December 2016. The medical records of 279 patients whose cervical cytology reported LSIL were reviewed. The prevalence of silent high grade cervical intraepithelial neoplasia (CIN 2/3) in LSIL cytology result was determined. The results of the cervical cytology after the patients completed the 2-year follow-up were evaluated. Results: During the present study period, 279 cases of LSIL in cytology result were enrolled. In women with LSIL in the cytology report, two-third were in pre-menopausal status. The prevalence of CIN 2/3 in LSIL cytology in women younger than 30 and 30 or older were 11.9% and 11.2%, respectively. At 2-year follow-up, around 97% of the patients who completed the follow-up had a spontaneous regression of the disease in both aged groups. Three percent of cases (3/85) had persistent disease in women 30 or older only. There was no progressive disease in the present study. Conclusion: Silent CIN 2/3 in LSIL cytology in the present study were high. Colposcopy should be recommended for diagnosis and follow-up in this setting. Abnormal Pap at 2-year follow-up was around three percent, therefore, abnormal cytology was still a problem. Continuous close cytology follow-up is still recommended. Keywords: Low-grade squamous intraepithelial lesion, LSIL, Cervical intraepithelial neoplasia, CIN, Cytology

Intraoperative Human Papillomavirus Test Predicts 24-Month High-Grade Squamous Intraepithelial Lesion Recurrence Saving Costs: A Prospective Cohort Study.

The human papilloma virus (HPV) test is recommended in the posttreatment follow-up of cervical intraepithelial neoplasia. The aim of the study was to assess whether the intraoperative HPV (IOP-HPV) test had a similar diagnostic accuracy that HPV test performed at 6 months to predict high-grade squamous intraepithelial lesion (HSIL) recurrence. In a prospective cohort study, 304 women diagnosed with HSIL by biopsy and/or endocervical curettage before treatment and/or confirmation in the histological specimen were included. Immediately after surgery, HPV testing was performed. This test was compared with the test at 6 months and other predictors of recurrence. Patients were followed for 24 months. An economic analysis was performed to compare the costs of IOP-HPV and HPV test at 6 months. Recurrence rate of HSIL was 6.2% (19 patients). The diagnostic accuracy of the IOP-HPV test to predict HSIL recurrence at 24 months was similar to the HPV test at 6 months, with comparative sensitivities of 100% versus 86.7%, specificities of 82.0% versus 77.9%, positive predictive values of 27.1% versus 18.1%, and negative predictive values of 100% versus 99.0%. Direct economic saving per high-grade intraepithelial lesion patient was 172.8 &OV0556;. The HPV test performed after loop electrosurgical resection procedure predicted recurrence of HSIL at 24 months with a similar diagnostic accuracy than the HPV test at 6 months. The use of the IOP-HPV test in the management of HSIL will allow early detection of the risk of recurrent disease and to save costs because of potential suppression of the need of HPV and follow-up controls at 6 months.

HPV-Based Screening, Triage, Treatment, and Followup Strategies in the Management of Cervical Intraepithelial Neoplasia

Cervical cancer is the second most common cause of death from cancer in women worldwide, and the development of new diagnostic, prognostic, and treatment strategies merits special attention. Many efforts have been made to design new drugs and develop immunotherapy and gene therapy strategies to treat cervical cancer. HPV genotyping has potentially valuable applications in triage of low-grade abnormal cervical cytology, assessment of prognosis and followup of cervical intraepithelial neoplasia, and in treatment strategies for invasive cervical cancer. It is known that during the development of cervical cancer associated with HPV infection, a cascade of abnormal events is induced, including disruption of cellular cycle control, alteration of gene expression, and deregulation of microRNA expression. Thus, the identification and subsequent functional evaluation of host proteins associated with HPV E6 and E7 oncoproteins may provide useful information in understanding cervical carcinogenesis, identifying cervical cancer molecular markers, and developing specific targeting strategies against tumor cells. Therefore, in this paper, we discuss the main diagnostic methods, management strategies, and followup of HPV-associated cervical lesions and review clinical trials applying gene therapy strategies against the development of cervical cancer.

Risk of cervical cancer after completed post-treatment follow-up of cervical intraepithelial neoplasia: population based cohort study

Objective To compare the risk of cervical cancer in women with histologically confirmed cervical intraepithelial neoplasia who returned to routine screening after having completed post-treatment follow-up with consecutive normal smear...

The role of HPV genotypes and persistence in follow-up of cervical intraepithelial neoplasia after treatment.

1561 Background: HPV testing is considered as an acceptable strategy for surveillance after treatment of cervical intraepithelial neoplasia (CIN). The role of high risk HPV (HR-HPV) genotypes and persistent infection in follow-up remains unclear. Methods: A prospective observational study was conducted on 249 patients with CIN (CIN1=11, CIN2=34, CIN3==204) after conization. Besides traditional follow-up with cytology and colposcopy, HPV genotyping test identifying 13 HR-HPVs (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) was performed every 6 months after treatment. Endpoint of this study was a histological confirmed CIN during follow-up. Results: 17 recurrences occurred during a median follow-up of 28 months. HR-HPV positive rate decreased over time (29.3% (73/249) for 6 months, 20.1% (50/249) for 12 months, and 15.3% (38/249) after 12 months, respectively). HR-HPV positive results predicted 88.2% (15/17) of recurrences. The most common HR-HPV genotypes appeared post-treatment were HPV 16 (19.3%), HPV 58 (12.0%), HPV 52 (8.0%), HPV18 (4.4%) and HPV33(4.0%). HPV 16, HPV 58 and HPV52 remained as the top three most frequent genotypes in type specific persistent infection. There was no correlation between recurrence and individual HR-HPV infections such as HPV 16, HPV 52 or HPV58 (P>0.05). Recurrent disease was more likely to occur in patients with multiple HR-HPV infection than with single infection (11/27 vs. 4/72, P<0.001). Persistent HR-HPV infection had a higher risk of recurrence than transient infection as compared to negative (hazard ratio [95%CI]: 28.8 [6.35-103.96] for persistence, 1.40 [0.12-14.35] for transition, P<0.0001). Type specific HPV infection had an elevated risk of recurrence (hazard ratio [95%CI]: 40.86 [9.01-185.36]). Conclusions: HPV genotyping test is useful in follow-up. Multiple HR-HPV infection and persistent especially type specific persistent HR-HPV infection indicates a higher risk of recurrence, unlike appearance of the most common HR-HPV genotypes (HPV16, 58, 52) post-treatment.

The role of HPV DNA testing in the follow-up of cervical intraepithelial neoplasia after loop electrosurgical excision procedure

To assess human papilloma viruses (HPV) DNA test for detection of recurrences in cervical intraepithelial neoplasia (CIN) patients after loop electrosurgical excision procedure (LEEP). Also effect of LEEP on the clearance of HPV infection was evaluated for CIN 1 lesions. HPV DNA positive 37 patients (25 CIN 2-3 and 12 CIN 1 cases proven by colposcopic biopsies) were treated with LEEP and followed prospectively with HPV DNA and cytology at third and sixth months. There were 11 patients with abnormal cytologic results in third month and 4 in sixth month. HPV DNA positivity rate declined in CIN 1 group between third and sixth month but this did not reach to statistical significance (44 vs. 36%, P = 0.41). There were 3 treatment failures out of 37 patients (8.1%). All these three patients had CIN 3 at the beginning and two of them had positive HPV DNA in two controls. There were no recurrence/treatment failure for CIN 1 patients. Regarding 37 patients, decrease in cytologic abnormality incidence between third and sixth-month control was statistically significant (29.7 vs. 10.9%, P = 0.03). All four patients with cytologic abnormality at the sixth month had HPV persistence. Cytologic abnormality was more prevelant in HPV persistent women (P = 0.01) and also there was no cytologic abnormality in case of HPV DNA negativity. LEEP does not seem to decrease HPV DNA incidence for CIN 1 at least for 6 months. But HPV DNA used in addition to cytology might help to detect recurrences.

Reasons for early interventions by gynaecologists in a clinical follow-up study on cervical intraepithelial neoplasia

Objective In a previous clinical follow-up study on psychosocial factors and cervical intraepithelial neoplasia (CIN), we had noticed a high percentage of early interventions to the cervix by gynaecologists, in discordance with the research protocol. The aim of the current study was to investigate the reasons for these interventions. Study design We retrospectively analysed the study records of the clinical study, concerning the follow-up of 98 patients with a CIN 1 or 2 lesion for 2.25 years by colposcopy and cervical smears. We recorded the number of early interventions that had occurred in the clinical study as well as the reasons for these interventions. A distinction was made between acceptable and unacceptable reasons for early intervention. Results During follow-up, 39 out of 98 women (40%) had undergone intervention in discordance with the protocol. No acceptable reason for these interventions was found for 67% of these patients (26/39). In the majority of these cases either no reason for the intervention had been given, or the gynaecologist had feared for progression of the CIN lesion. Conclusion Gynaecologists tend to intervene during follow-up of CIN, partly out of fear for progression. This tendency may complicate follow-up studies on CIN.

Comparison between the Hybrid Capture II Test and a PCR-Based Human Papillomavirus Detection Method for Diagnosis and Posttreatment Follow-Up of Cervical Intraepithelial Neoplasia

Human papillomavirus (HPV) infection is the major cause of cervical cancer and its precursor, cervical intraepithelial neoplasia (CIN), and HPV testing has therefore been proposed for improved triaging and follow-up of women treated for CIN. We compared two common HPV DNA detection tests (Hybrid Capture II [HCII] and PCR-enzyme immunosorbent assay (EIA) using the primers GP5+/GP6+ followed by HPV typing with reverse dot blot hybridization) for sensitivity and specificity for detection of CIN and of CIN recurrence after treatment. Two hundred and thirty-nine women referred to the Department of Obstetrics and Gynaecology in Västerås, Sweden, were enrolled because of atypical Pap smears; 177 of these were later treated for dysplasia by conization or loop diathermy. Samples for HPV DNA testing were taken before and 4 to 6 months after treatment. There was substantial agreement between the HCII and PCR-EIA (kappa, 0.70 before treatment and 0.72 after treatment). The sensitivity for histopathologically confirmed CIN III was 100.0% for PCR-EIA and 95.6% for HCII. For patients with CIN II or worse (CIN II+), the sensitivities were 92.9% (PCR-EIA) and 91.8% (HCII). The specificities for CIN II+ in the pretreatment setting were 30.4% for PCR-EIA and 24.1% for HCII. After treatment, the sensitivities for CIN III in cytology were 100.0% by both methods, and for CIN II+, sensitivities were 80.0% by both methods. The specificities for CIN II+ in the posttreatment setting were 83.5% for PCR and 85.4% for HCII. In conclusion, the sensitivities of both PCR-EIA and HCII are high and almost equal, suggesting that both methods are suitable as tools for detection and posttreatment follow-up of CIN II-III.

Demographic variables routinely collected at colposcopic examination do not predict who will default from conservative management of cervical intraepithelial neoplasia I

As a result of the low incidence of progression from low grade epithelial abnormalities to cervical intraepithelial neoplasia (CIN) 3 or cervical cancer, a conservative approach to management is supported, especially in young women. Loss to follow-up is a recognised problem with a conservative approach however, with women defaulting known to experience higher rates of cancer. To determine if any routinely collected demographic variables could predict which Australian women would subsequently default from care having initially elected to have conservative management of CIN 1 lesions. Prospectively collected data was audited on 279 women with a colposcopically directed biopsy diagnosis of CIN 1, confirmed on external review, who were enroled by their own choice into a conservative management program and monitored until a definitive lesion outcome was determined. Women who defaulted from follow-up and were lost to care providers despite follow-up appointments and reminder letters were compared to women who completed follow-up with either lesion resolution or progression requiring treatment, to establish if there were any demographic variables to predict default from care. Fifty-two (18.5%) women subsequently defaulted from follow-up. There were no significant differences in age, parity, proportion of women who were pregnant at diagnosis, smoking status, immunosuppressed or had a 'human papillomavirus (HPV) effect' reported on Pap-smear or colposcopic examination. We cannot easily identify a subgroup of women who are more likely to default from follow-up of CIN 1 using routinely collected demographic data. Default from follow-up is a major risk with conservative approaches and further research to reduce default rates are required.

The Ki-67 Labeling Index Is Not a Useful Predictor for the Follow-up of Cervical Intraepithelial Neoplasia 1

Our aim was to determine whether the Ki-67 immunostaining pattern, present on diagnosis of cervical intraepithelial neoplasia (CIN), predicts the change from low-grade to high-grade CIN over a 2-year period after diagnosis. Of 59 cervical biopsy samples from 59 patients diagnosed as having cervical CIN, 35 were diagnosed as CIN 1 and 24 were diagnosed as CIN 2 or CIN 3. The Ki-67 immunostain showed immunopositive cells in the upper two thirds of the epithelium in all specimens. Two hundred nuclei were counted in 25 high-power fields in each specimen, including all of the epithelial layers, to determine the mean number of Ki-67-positive cells. In situ hybridization was used to demonstrate and type human papillomavirus. The chi test, Fisher exact test, Student t test, one-way analysis of variance, and Tukey test were used for statistical analysis, with significance set at p < .05. The mean Ki-67 labeling index for CIN 1, CIN 2, CIN 3, and CIN 2,3 were, respectively, 32.5%, 43.2%, 53.2%, and 47.8%. The statistical study showed significant differences between CIN 1 versus CIN 2, CIN 1 versus CIN 3, and CIN 1 versus CIN 2,3. For CIN 1, the mean Ki-67 labeling index was 32.8% when the lesion disappeared and was 34.6% for persisting lesions. There was no statistically significant difference. Ki-67 labeling index did not predict persisting CIN 1.

Long-term follow-up of cervical intraepithelial neoplasia treated with minimal conization by carbon dioxide laser.

Minimal conization with carbon dioxide laser (CO2) for safe diagnosis and treatment of cervical intraepithelial neoplasia (CIN) 1-3 has been utilized for 15 years. To evaluate the results of 15 years' follow-up. Clinical prospective study: 2,903 non-pregnant women whose cervicovaginal smear revealed CIN 1-3, confirmed by colposcopy, were referred for minimal conization treatment (LMC). This outpatient free-hand excision is performed under local anesthesia with a 60-W continuous laser beam focused to a 0.1-mm spot size, giving a power density of 165,000 W/cm2. Adjuvant cervical curettage is done routinely. Complications after the procedure were insignificant. Histopathological investigations revealed invasive carcinoma in 1.2% of the minicones. The primary cure rate was 96.1%. In the life table analysis of the patients the cumulative risk of recurrence for all forms of CIN was 0.89% at year 5, 1.36% at year 10, and 3.02% at year 15. There was no sudden onset carcinoma during the follow-up period. Minimal conization is a safe, effective treatment for CIN and early forms of microinvasive carcinoma. Invasive carcinoma can be detected early and should be treated without delay. The cumulative risk of developing new CIN is 3.02% at year 15 and there is no risk of sudden-onset invasive carcinoma following this procedure.