Recurrent Cervical Intraepithelial Neoplasia Research Articles

Risk of persistent and recurrent cervical neoplasia following incidentally detected adenocarcinoma in situ

Adenocarcinoma in situ of the uterine cervix is a precursor to cervical adenocarcinoma and may coexist with both adenocarcinoma and high-grade squamous dysplasia (cervical intraepithelial neoplasia 2 and 3). Up to 60% of adenocarcinoma in situ lesions are detected incidentally following excisional biopsies performed for the treatment of cervical intraepithelial neoplasia 2/3. To date there are no data regarding risk factors for persisting or progressive cervical neoplasia in these patients. We sought to investigate patient outcomes following incidentally detected cervical adenocarcinoma in situ after loop electrosurgical excision procedure or cold knife cone biopsy performed for the treatment of high-grade cervical intraepithelial neoplasia. We conducted a retrospective, population-based cohort study of Western Australian patients with an incidental diagnosis of adenocarcinoma in situ from 2001 through 2012. Primary outcomes were persistent or recurrent cervical intraepithelial neoplasia 2/3 and or adenocarcinoma in situ, and invasive adenocarcinoma during follow-up (<12 months) and surveillance (≥12 months) periods. The cohort comprised 298 patients, with 228 (76.5%) treated initially by loop electrosurgical excision procedure and 70 (23.5%) treated by cold knife cone biopsy. The mean age was 31.2 (range 18-68) years and the median length of follow-up was 2.4 (range 0.3-12.2) years. Overall, 11 (3.7%) patients had cervical intraepithelial neoplasia 2/3, 23 (7.7%) had adenocarcinoma in situ, and 3 (1.0%) had adenocarcinoma diagnosed during the follow-up and surveillance periods. Age >30 years, pure adenocarcinoma in situ lesions, and larger lesions (>8 mm) were associated with a greater risk of disease persistence or recurrence. Following the incidental detection of adenocarcinoma in situ, age >30 years, pure adenocarcinoma in situ lesions, and lesions >8 mm were significantly associated with disease persistence/recurrence.In younger women, incidentally detected adenocarcinoma in situ that coexists with cervical intraepithelial neoplasia 2/3 and is <8 mm extent with clear margins may not require reexcision.

Good performance of p16/ki-67 dual-stained cytology for surveillance of women treated for high-grade CIN.

Women treated for high-grade cervical intraepithelial neoplasia (CIN) are at risk of recurrent CIN Grade 2 or worse (rCIN2+). Currently, posttreatment monitoring is performed using cytology or cytology/high-risk (hr)HPV cotesting. This study aimed to evaluate the performance of p16/Ki-67 dual-stained cytology (p16/Ki-67) for posttreatment monitoring. Three hundred and twenty-three women treated for high-grade CIN in the SIMONATH study underwent close surveillance by cytology, hrHPV and DNA methylation marker testing up to 12 months posttreatment. Histological endpoints were ascertained by colposcopy with biopsy at 6 and/or 12 months. p16/Ki-67 dual-staining was performed on residual liquid-based cytology samples obtained at, or shortly before biopsy collection. Clinical performance estimates of cytology, hrHPV, p16/Ki-67 testing and combinations thereof for the detection of rCIN2+ were determined and compared to each other. Sensitivity of p16/Ki-67 for rCIN2+ (69.2%) was nonsignificantly lower than that of cytology (82.1%; ratio 0.84, 95% CI: 0.71-1.01), but significantly lower than that of hrHPV testing (84.6%; ratio 0.82, 95% CI: 0.68-0.99). Specificity of p16/Ki-67 for rCIN2+ (90.4%) was significantly higher compared to both cytology (70.8%; ratio 1.28, 95% CI: 1.19-1.37) and hrHPV testing (76.2%; ratio 1.19, 95% CI: 1.12-1.26). Overall, hrHPV testing showed very high sensitivity, along with a good specificity. When considering cotesting, combined p16/Ki-67/hrHPV testing showed rCIN2+ sensitivity comparable to cytology/hrHPV cotesting (87.2% vs. 89.7%; ratio 0.97, 95% CI: 0.92-1.03), but with significantly increased specificity (74.2% vs. 58.1%; ratio 1.28, 95% CI: 1.19-1.38). Thus, when considered in combination with hrHPV, p16/Ki-67 might be an attractive approach for surveillance of women treated for high-grade CIN.

Prior human papillomavirus-16/18 AS04-adjuvanted vaccination prevents recurrent high grade cervical intraepithelial neoplasia after definitive surgical therapy: Post-hoc analysis from a randomized controlled trial.

We evaluated the efficacy of the human papillomavirus (HPV)−16/18 AS04‐adjuvanted vaccine in preventing HPV‐related disease after surgery for cervical lesions in a post‐hoc analysis of the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681). Healthy women aged 15–25 years were randomized (1:1) to receive vaccine or control at months 0, 1 and 6 and followed for 4 years. Women were enrolled regardless of their baseline HPV DNA status, HPV‐16/18 serostatus, or cytology, but excluded if they had previous or planned colposcopy. The primary and secondary endpoints of PATRICIA have been reported previously; the present post‐hoc analysis evaluated efficacy in a subset of women who underwent an excisional procedure for cervical lesions after vaccination. The main outcome was the incidence of subsequent HPV‐related cervical intraepithelial neoplasia grade 2 or greater (CIN2+) 60 days or more post‐surgery. Other outcomes included the incidence of HPV‐related CIN1+, and vulvar or vaginal intraepithelial neoplasia (VIN/VaIN) 60 days or more post‐surgery. Of the total vaccinated cohort of 18,644 women (vaccine = 9,319; control = 9,325), 454 (vaccine = 190, control = 264) underwent an excisional procedure during the trial. Efficacy 60 days or more post‐surgery for a first lesion, irrespective of HPV DNA results, was 88.2% (95% CI: 14.8, 99.7) against CIN2+ and 42.6% (−21.1, 74.1) against CIN1+. No VIN was reported and one woman in each group had VaIN2+ 60 days or more post‐surgery. Women who undergo surgical therapy for cervical lesions after vaccination with the HPV‐16/18 vaccine may continue to benefit from vaccination, with a reduced risk of developing subsequent CIN2+.

Diagnostic value of human papillomavirus E6/E7 mRNA for residue and recurrence after cervical conization

To explore the diagnostic value of human papillomavirus E6/E7 mRNA for residue and recurrence of cervical intraepithelial neoplasia (CIN) patients after cervical conization. A total of 154 patients, who underwent cervical conization and possessed complete follow-up data of high-grade cervical intraepithelial neoplasia (CINII, III), were subjected to thin-prep cytology test (TCT), HPV-DNA typing and HPV E6/E7 mRNA test in 3-6 months and 12 months after cervical conization. Abnormal cytology (≥ASC-US) or high-risk HPV-DNA (+) or HPV E6/E7 mRNA (+) cases were found by colposcopy and cervical biopsy pathological diagnosis. Nine patients had residue and 22 recurred. HPV-DNA detections after cervical conization in 57 patients were positive. Among them, 30 patients had residual/recurrent lesions. HPV E6/E7 mRNA detections in 26 patients were positive. Among them, 24 patients had residual/recurrent lesions. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of diagnosis in the detection of HPV-DNA were 96.8%, 78%, 52.6%, 99%, and 81.8%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of diagnosis in the detection of HPV E6/E7 mRNA were 77.4%, 98.4%, 92.3%, 94.5%, and 94.2%, respectively. The specificity and positive predictive value of HPV E6/E7 mRNA test were greater than those of HPV-DNA typing test. There was a significant difference between the two groups (P<0.05). Detection of HPV E6/E7 mRNA during the follow-up period could timely and effectively forecast the risk of residue and recurrence of CIN after cervical conization, and reduce excessive examination and treatment.

Risk factors for residual disease after cervical conization in patients with cervical intraepithelial neoplasia grades 2 and 3 and positive surgical margins

ObjectiveTo evaluate risk factors for the persistence of cervical intraepithelial neoplasia (CIN) grade ≥2 following repeat surgical procedures in patients with CIN grades 2 and 3 and positive surgical margins. Study designThis study included patients with CIN grades 2 and 3 and positive surgical margins following loop electrosurgical excision procedures (LEEP), who had undergone additional surgery between 2007 and 2014. Factors associated with CIN grade ≥2 on biopsy results after the second operation were assessed by multiple logistic regression analysis. Factors considered included patient age, parity, menopausal status, smoking, referral cytology, initial LEEP pathology, time interval between LEEP and surgical procedures, presence of disease on endocervical sampling, endocervical surgical margins, glands, disease surrounding ≥50% of the cervical circumference and requirement for multiple sweeps on initial LEEP to excise a lesion. The forward likelihood ratio method was used and significance was set at p<0.05. ResultsRepeat surgical procedures were performed in 104 patients, 75 with CIN 2 and 29 with CIN 3, with 43 (41.3%) reported as normal or CIN 1. However, 57 (54.8%) patients had CIN ≥2 lesions and four (3.8%) had previously undiagnosed cervical cancer. Factors associated with CIN ≥2 lesions included requirement for multiple sweeps (vs. a single sweep; odds ratio [OR] 5.967; 95% confidence interval [CI] 2.183–16.311, p<0.001) and involvement of ≥50% of the cervical circumference (vs. <50%; OR 5.073; 95% CI 1.501–17.146, p=0.009). ConclusionAs lesions requiring multiple sweeps for excision and/or surrounding ≥50% of the cervical circumference during initial conization are associated with recurrent CIN ≥2 lesions, attention should be paid during resection to prevent margin positivity. If surgical margins are positive, however, repeat surgical procedures should be considered in patients with CIN 2 and CIN 3 lesions and these risk factors.

Human papillomavirus genotyping as a reliable prognostic marker of recurrence after loop electrosurgical excision procedure for high-grade cervical intraepithelial neoplasia (CIN2-3) especially in postmenopausal women.

This study was conducted to determine, using the HPV DNA Chip (HDC) test, whether the human papillomavirus (HPV) genotype is predictive of recurrent high-grade cervical intraepithelial neoplasia (CIN; CIN2-3) after a loop electrosurgical excision procedure (LEEP) in postmenopausal women. Between January 2007 and February 2013, 206 postmenopausal women with CIN2-3 were treated with LEEP, followed by cytology, Hybrid Capture II (HC2) assay, and HDC test. Post-LEEP follow-up was performed at 3, 6, 9, 12, 18, and 24 months during the first 2 years and yearly thereafter. Among 206 women, HC2 yielded positive results in 199 women (96.6%) and HDC yielded positive results in 201 women (97.6%) before LEEP. The overall agreement between HDC and HC2 was 99.0%. The area under the receiver operating characteristic curve for high-risk HPV (HR-HPV) viral load measured by HC2 predicting recurrent CIN2-3 was 0.567 (P = 0.335). Twenty-six women (12.6%) developed recurrence, and those who developed recurrence tested positive for the same HR-HPV genotype before and after LEEP. The same HR-HPV genotype by HDC during follow-up had a sensitivity and negative predictive value of 100% in detecting recurrent disease. HPV-18 was significantly associated with recurrent CIN2-3 (P < 0.05). Among postmenopausal women, persistent infection with the same HR-HPV genotype, especially HPV-18, should be considered a risk factor for developing recurrent CIN2-3. After LEEP, such women warrant special attention with intense follow-up.

Posttreatment human papillomavirus testing for residual or recurrent high-grade cervical intraepithelial neoplasia: a pooled analysis.

ObjectiveWe conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3).MethodsSource articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013.ResultsThe pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p<0.001).ConclusionOur findings recommend the addition of high-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins.

New technologies in diagnosis of preinvasive cervical lesions

Results of efficiency assessment of different diagnosis for preinvasive cervical lesions are represented in the article. During investigation the retrospective analysis of 353 patient histories of women with cervical intraepithelial neoplasia (primary and recurrent), who have been observed in Ivanovskiy regional oncological dispensary from 2002 to 2011, was performed. The accuracy rates of diagnosis of cervical intraepithelial neoplasia for one or several methods including cytological study, colposcopy and fluorescence cystoscopy were compared. Fluorescence diagnosis was performed with drug fotoditazin (LLC «VETA-GRAND», marketing authorisation №LS 001246) at dose of 1,0 mg/kg body weight. The final diagnosis was determined by results of histological study. The accuracy of cytological study accounted for 67,5–80,7%. Using colposcopy the exact diagnosis was determined in 67,9–74,4% of cases. Combination of cytological study with colposcopy improved the accuracy of diagnosis up to 82.1–88.9%. The superior results were for concurrent use of cytological study with colposcopy and fluorescence diagnosis – in such case the diagnosis was correct in 92,0–96,7% of patients. The analysis of results showed that using all methods of diagnosis the accuracy of diagnosis for recurrent cervical intraepithelial neoplasia was lower than for primary lesions. The decrease of diagnosis accuracy is probably related to previous diagnosis and therapeutic manipulations on cervix. Thus, multimodal diagnosis investigation with methods of fluorescence spectroscopy allows to improve accuracy of diagnosis for preinvasive cervical lesions.

Clinical effectiveness of VIA and colposcopy based management of cervical intraepithelial neoplasia

Cervical cancer develops from early precancerous lesion known as cervical intraepithelial neoplasia (CIN). Khulna Medical college Hospital provides primary screening for preventing cervical cancer and a secondary referral centre for management of CIN by colposcopy. Primary objective of this study was to do an audit between January 2012 to February 2014 to update clinical efficacy of colposcopy based diagnosis, treatment and follow up of 510 CIN cases and also to document any shortcomings in existing services and suggestion for early rectification. Colposcopic findings in our study group were: 309(60.6%) cases were CIN-1, 124 (24.3%) cases was CIN II, and 49 (9.6%) cases were CIN III. Suspicious of invasive lesion was in 7 (1.4%) abnormal looking cervix and biopsy was done in 21(4.1%). Treatment procedure was done with individualization of cases and options were cold coagulation, Loop electrosurgical excision procedure (LEEP), hysterectomy, biopsy and post treatment follow up. Histopathological diagnosis was documented in 387 cases, where CINI was found in 161 (31.6%), CIN II in 92 (18%), CIN III in 26 (5.1%), non specific Inflammatory cervicitis in 87(17.1%), Squamous cell carcinoma in 15(2.9%), abnormalities consistent with koilocytic atypia in 6 (12%) and reports missed in 123 (24.1%). Cases results showed Positive predictive value (PPV) of 53% and 68% respectively for low grade (CIN I) and high grade lesion (CIN II, III). 481 patient were eligible for post treatment follow up but only 99 (20.5%) patient came and among them 74 (74.7%) were colposcopically negative, 25 (25.2%) had residual CIN and Risk Ratio (RR) was 0.25. Colposcopy is gold standard for diagnosis of CIN but our screening program is opportunistic and far way from population based. Histopathological correlation were often inaccurate with colposcopic diagnosis in practice and about one third case reports were missed. Majority of women did not complete follow up protocol. Residual or recurrent CIN lesion in dropped out cases would be a concern in near future. DOI: http://dx.doi.org/10.3329/bmjk.v47i1-2.22557 Bang Med J (Khulna) 2014; 47 : 16-20

Follow-up strategies after treatment (large loop excision of the transformation zone (LLETZ)) for cervical intraepithelial neoplasia (CIN): Impact of human papillomavirus (HPV) test

Development of cancer of the cervix is a multi-step process as before cervical cancer develops, cervical cells undergo changes and become abnormal. These abnormalities are called cervical intraepithelial neoplasia (CIN) and are associated with increased risk of subsequent invasive cancer of the cervix. Oncogenic high-risk human papillomavirus (hrHPV), the causative agent of cervical cancer and its precursor lesions, is present in up to one-third of women following large loop excision of the transformation zone (LLETZ) treatment and is associated with increased risk of residual disease and disease recurrence.HPV testing may serve as a surveillance tool for identifying women at higher risk of recurrence. High-risk human papillomavirus testing will enable us to identify women at increased risk of residual or recurrent CIN and therefore will allow us to offer closer surveillance and early treatment, when indicated. • To evaluate the effectiveness and safety of hrHPV testing after large loop excision of the transformation zone (LLETZ) treatment• To determine optimal follow-up management strategies following LLETZ treatment according to hrHPV status We searched the Cochrane Gynacological Cancer Review Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed and PsycINFO up to August 2013. We searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies, and we contacted experts in the field. We searched for randomised control trials (RCTs) that compared follow-up management strategies following LLETZ treatment for CIN. Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found; therefore no data were analysed. The search identified 813 references on MEDLINE, 418 on EMBASE, 22 on CINAHL, 666 on PubMed, 291 on PsycINFO and 145 on CENTRAL. When all references were imported into EndNote and duplications were removed, 1348 references remained. Initial screening of titles and abstracts of these references revealed that 42 references were potentially eligible for this review. After reading the full-text versions, we identified no relevant trials comparing hrHPV and cytology testing versus cytology testing alone for detecting residual or recurrent disease during follow-up to LLETZ treatment of adult women with CIN.We found no evidence on the effects of hrHPV and cytology testing on residual or recurrent CIN2 or higher lesions, anxiety and psychosexual morbidity outcomes in women undergoing colposcopy and treatment for CIN. We found no evidence from RCTs to inform decisions about the best surveillance strategy for women following treatment for CIN. A prognostic systematic review is needed to investigate the risk of developing recurrent cervical intraepithelial neoplasia 2+ (CIN2+) in women with a positive hrHPV test after large loop excision of the transformation zone (LLETZ) treatment.

Analysis of factors associated with recurrence of cervical intraepithelial neoplasia after loop electrosurgical excision procedure

To explore the factors associated with recurrence of cervical intraepithelial neoplasia (CIN) after loop electrosurgical excision procedure (LEEP). A total of 236 patients with CIN owing to high-risk human papillomavirus (HPV) infection underwent LEEP and followed up with thinprep cytologic test (TCT), HPV genotype test and biopsy histology. Among them, 22 patients (9.3%) developed recurrent disease at 12 months post-LEEP. And the persistent infection rate of high-risk HPV was 10.6% (25/236). The odds ratio for recurrent CIN in patients with persistent infection of high-risk HPV was 38.9 (P < 0.01). Recurrent rate was associated with HPV DNA load pre-LEEP (P < 0.05), HPV16 infection (P < 0.01) and positive margin (P < 0.05). HPV DNA load >1 000 RLU/CO, HPV 16 infection and positive margin are risk factors for recurrence. And persistent infection of high-risk HPV is a significant predictor of recurrent CIN.

Successful pregnancy and full-term delivery after atypical polypoid adenomyoma of the uterus and recurrent cervical intraepithelial neoplasia 3

We describe a conservative treatment for atypical polypoid adenomyoma (APA) of the uterus and cervical intraepithelial neoplasia (CIN) 3 followed by a spontaneous pregnancy and full-term delivery in a 27-year-old woman. The patient presented with CIN 3 and underwent repeated Shimodaira–Taniguchi conization and treatment for APA. Medroxyprogesterone acetate (MPA) and low-dose aspirin were administered for 9 months followed by a hysteroscopic transcervical resection (TCR) of residual lesions. Atypical glands were <1 % of all glands. Three months later, the endometrium was fully recovered and biopsies revealed no atypical cells. Further 3 months later, the patient spontaneously conceived and gave birth to a healthy baby boy at full term. To the best of our knowledge, this is the first report on the use of MPA and TCR for treatment of APA patients, followed by a successful pregnancy outcome.

Prognostic scores after surgical treatment for cervical intraepithelial neoplasia: a proposed model and possible implications for post-operative follow-up.

To develop a prognostic model for women who underwent surgical treatment for cervical intraepithelial neoplasia. Cohort study. Patient inclusion and follow-up occurred retrospectively and prospectively. Barretos Cancer Hospital, Barretos, São Paulo, Brazil. Women (n=242) diagnosed with cervical intraepithelial neoplasia who were submitted to conization. Immediately prior to surgical treatment, a cervical cytology sample was collected from each individual included in the study by endocervical brushing and stored in a preservative solution with methanol. A human papilloma virus-DNA test was conducted using an aliquot of the endocervical brushings. The surgical specimens were subjected to immunohistochemical analysis of p16 (immunohistochemical analysis 4a) protein expression. Two-year disease-free survival rates calculated for each study variable. Identified variables in the multivariate Cox model were used for elaboration of prognostic scores. Variables associated with outcome included age (p=0.033), tobacco use (p<0.001), final histopathological diagnosis (p=0.007), surgical margins (p<0.001), high-risk human papilloma virus status (p=0.008), human papilloma virus-16 status (p<0.001) and immunoexpression of p16 in the cytoplasm (p=0.049). By the Cox model, independent risk factors for disease recurrence/persistence were: tobacco use (hazard risk=3.0; 95% confidence interval 1.6-5.6), positive surgical margins (hazard risk=3.2; 95% confidence interval 1.6-6.1), human papilloma virus-16 (hazard risk=3.3; 95% confidence interval 1.6-6.9) and age over 45years (hazard risk=2.7; 95% confidence interval 1.1-6.6). Establishment of a prognostic score can represent a valuable tool for determining the risk of cervical intraepithelial neoplasia recurrence after conization. The use of clinical (age and tobacco use), pathological (surgical margins) and molecular (human papilloma virus-16 genotyping) factors can facilitate more appropriate patient follow up according to risk stratification.

Unique recurrence patterns of cervical intraepithelial neoplasia after excision of the squamocolumnar junction.

Recent studies have identified a putative cell of origin for cervical intraepithelial neoplasia (CIN) and cervical cancer at the squamocolumnar junction (SCJ) and suggest that these cells may not regenerate after excision (loop electrosurgical excision procedure). Our study addressed the impact of SCJ excision on the temporal dynamics, histologic and viral (human papillomavirus, HPV) characteristics of recurrent CIN. One hundred and thirty-one consecutive patients treated by excision and attending follow-up visits were enrolled. We compared recurrent and initial CIN with attention to excision margins, timing of recurrence, CIN grade, HPV types, p16 immunophenotype and SCJ immunophenotype. During the follow-up period (up to 4 years), 16 (12.2%) recurrences were identified. Four (25%) were identified at the first follow-up visit, closely resembled the initial CIN 2/3 in grade and HPV type and were typically SCJ marker positive [SCJ(+)], suggesting nonexcised (residual) disease. Twelve (75%) manifested after the first postoperative visit and all were in the ectocervix or in mature metaplastic epithelium. All of the 12 delayed recurrences were classified as CIN 1 and were SCJ (-). In total, 9 out of 11 SCJ (-) recurrences (82%) followed regressed spontaneously. Taken together, these results show that new lesions developing from any HPV infection are delayed and occur within the ectocervix or metaplastic epithelium. This markedly lower risk of CIN 2/3 after successful SCJ excision suggests that the removal of the SCJ could be a critical variable in reducing the risk of subsequent CIN 2/3 and cervical cancer.

Cervical intraepithelial neoplasia in a cohort of HIV-positive women at the University Hospital of the West Indies: management and outcome.

To determine the rate of recurrence of cervical intraepithelial neoplasia (CIN) in HIV-positive women evaluated at the University Hospital of the West Indies (UHWI). A chart review of all non-pregnant HIV-positive women who attended the gynaecologic and colposcopic clinics between January 1994 and December 2004 identified 21 such women. Fifteen of these patients who had CIN and had at least one follow-up Pap smear were the main subjects of this study. These patients were compared to 21 HIV-negative controls who were seen during the same period and who also had at least one follow-up Pap smear. Treatment modalities for the groups included cold coagulation and large loop excision of the transformation zone (LLETZ). Cox proportional hazards analysis was used to determine the effect of HIV status on the time to first recurrence of CIN. The mean ages of the subjects were 32.7 ± 8.0 and 33.2 ± 8.1 years, respectively. With a mean follow-up period of 1.7 years, the rate of recurrence of CIN in patients with and without HIV was 66.24 (95% CI 27.6, 159.1) and 3.0 (95% CI 1.3, 7.3) per 100 person years. The hazards rate ratio for recurrence in subjects with HIV after adjusting for age and CIN stage was 19.1 (95% CI 4.4, 82.1). HIV increases the risk of recurrence of CIN.

Factors Associated With Recurrence of Cervical Intraepithelial Neoplasia 2+ After Treatment Among HIV-Infected Women in Western Kenya

HIV-infected women are at increased risk for recurrence of cervical dysplasia after treatment. Short-term recurrence rates may reflect treatment efficacy and therefore impact screening protocols and follow-up planning. We conducted a prospective study of 297 HIV-infected women undergoing loop electrosurgical excision procedure for cervical intraepithelial neoplasia 2+ (CIN2+) in an HIV clinic in Kisumu, Kenya. By 6 months after the procedure, 20 (7.1%) of women had recurrent CIN2+. Recurrence was significantly associated with CD4 nadir but not with highly active antiretroviral therapy use. Longer-term follow-up of this cohort will illustrate the potential impact of highly active antiretroviral therapy and immune status on CIN2/3 disease recurrence.

Recurrent high-grade cervical lesion after primary conization is associated with persistent human papillomavirus infection in Norway

ObjectiveThis retrospective registry-based study aimed to assess the human papillomavirus (HPV)-type distribution in primary and recurrent high-grade cervical intraepithelial neoplasia (CIN2+), and to discriminate pre-existing from newly-acquired infections. MethodsCervical specimens from 58 women (median age (Q1–Q3): 37.6 (31.7–44.9)) who underwent primary (1998–2003) and repeat conizations were confirmed as CIN2+ during expert pathology review. HPV testing was performed using PCR MP-TS123 Luminex for 16 HPV types. Molecular HPV16 E6 and HPV18 LCR DNA sequencing was performed on specimens with persistent HPV16/18. ResultsAll 58 paired cones were HPV positive; 49 had CIN3+ in the primary cone. Forty-seven (95.9%) women with primary CIN3+ and recurrent CIN2+ had persistent high-risk (hr) HPV infection, of which 74.5% were HPV16/18. Two women had probable newly-acquired HPV16/52/56 and HPV39 infections. One woman with persistent HPV52 also had a probable new HPV16 E6 variant in the recurrent CIN2+. Median time delay (Q1–Q3) between conizations was 2.0years (1.1–4.0), being shorter for women older than 40years: 2.6years (1.1–3.7) than for women younger than 40years: 6.0years (2.0–8.7). Primary conization histology revealed CIN3, cervical adenocarcinoma in situ and microinvasive carcinomas in 43 (87.8%), 5 (10.2%) and 1 (2.0%) women, respectively. Primary HPV16- and HPV18-infected CIN3+ had a shorter delay between conizations: 1.8years (1.2–4.4) and 2.2years (0.4–NE), respectively, compared to HPV33-: 3.8years (3.3–7.8) or other HPV type-infected: 8.2years (6.0–NE) CIN3+. ConclusionsRoutine post-conization hr-HPV DNA testing together with cervical cytology may provide a better prediction for potential recurrent disease. Further, primary prevention through adolescent vaccination may prevent CIN2+ and its recurrence.

Human papillomavirus type‐specific persistence and recurrence after treatment for cervical dysplasia

Human papillomavirus (HPV) infection is a necessary factor in the cervical cancer development. Also after treatment for cervical dysplasia, HPV can be present and promote the recurrence of cervical disease. In the present study, the aim was to perform a long-term follow-up on the ability of HPV testing with genotyping, as compared with cytology, to predict recurrence of high-grade cervical intraepithelial neoplasia and to evaluate the effectiveness of treatment with loop electrosurgical excision procedure (LEEP) conization. Cervical samples for HPV DNA testing and cytological analysis were obtained from 178 women with abnormal smears referred for treatment with LEEP conization. These women were scheduled for HPV DNA testing and Pap smears before and 3, 6, 12, 24, and 36 months after treatment. Three years after treatment 3.1% (N = 4) of women were still persistently HPV-positive with the same type as had been detected at treatment. Recurrent or residual cervical intraepithelial neoplasia II+ in histopathology was found among 9 (5.1%) women during follow-up. All of these women had type-specific HPV-persistence (sensitivity 100% [95% CI 63-100%] and specificity 94.7% [89.8-97.4%]), but only 7/9 had abnormal cytology (sensitivity 77.8% [40.2-96.1%] and specificity 94.7% [89.8-97.4%]). No recurrent or residual disease was found among women with any other patterns of HPV positivity (e.g., type change or fluctuating positivity) (sensitivity 0% [95% CI 0-37.1%] and specificity 80.5% [73.5-86.0%]). In conclusion, only type-specific HPV persistence predicted recurrent or residual disease, and HPV genotyping appears useful to improve the specificity when using HPV testing in post-treatment follow-up.

Photodynamic therapy for management of cervical intraepithelial neoplasia II and III in young patients and obstetric outcomes

To evaluate the response and efficacy of photodynamic therapy (PDT) with or without loop electrosurgical excision procedure (LEEP)/conization (Cone) to preserve fertility in young patients with cervical intraepithelial neoplasia (CIN) II and III. We reviewed the medical records of patients with CIN who had been treated by PDT. Among a total of 73 patients who received PDT for CIN II/III between September 2000 and August 2011, 59 patients aged 40 or younger and who wished to preserve fertility were included. Patients were divided into four groups: group (I) only PDT without LEEP (n = 13), group (II) PDT combined with LEEP/Cone (n = 15), group (III) PDT due to positive LEEP/Cone margin (n = 25), group (IV) PDT for recurrent CIN after LEEP/Cone (n = 6). Surface photoillumination with red laser light at a wavelength of 630 nm was applied to the uterine cervix and endocervical canal of patients 48 hours after an intravenous injection of 2 mg/kg of photosensitizer. The median age of the 59 patients (CIN 2: 4, CIN 3: 22, carcinoma in situ: 31, adenocarcinoma in situ: 2) was 30.4 years. Twenty-two patients were unmarried and 38 were nulliparous. The complete remission (CR) rate was 98.1% (52/53) at 1 year follow-up except six patients followed up loss. The remaining one had recurred at 1 year after PDT, and one residual case at 3 months follow-up was regarded as CR showing NED after secondary PDT. Human papilloma virus (HPV) typing was performed. Before treatment HPV infection rate was 96.3% (52/54). HPV DNA could be no longer detected in 89.8% (44/49) and 87.0% (40/46) at 3 and 12 months after PDT. Among 29 patients who tried to be pregnant, 18 patients achieved 25 pregnancies (6 abortions, 1 ectopic, 1 preterm, 15 term, and 2 ongoing pregnancies.) There has been no fetal loss due to incompetent internal os of cervix. For adverse events, photosensitivity occurred in 13.6% (8/59) and cervical stenosis occurred in one patient. PDT combined with or without LEEP/Cone may be a potential alternative for effective conservative treatment of CIN in young patients who wish to preserve fertility.

Prevalence, characteristics, and outcomes of HIV-positive women diagnosed with invasive cancer of the cervix in Kenya

ObjectiveTo determine the prevalence of invasive cervical cancer (ICC) and assess access to, and outcomes of, treatment for ICC among HIV-infected women in Kisumu, Kenya. MethodsWe performed a retrospective chart review to identify women diagnosed with ICC between October 2007 and June 2012, and to examine the impact of a change in the referral protocol. Prior to June 2009, all women with ICC were referred to a regional hospital. After this date, women with stage IA1 disease were offered treatment with loop electrosurgical excision procedure (LEEP) in-clinic. ResultsOf 4308 women screened, 58 (1.3%) were diagnosed with ICC. The mean age at diagnosis was 34years (range, 22–50years). Fifty-four (93.1%) women had stage IA1 disease, of whom 36 (66.7%) underwent LEEP, 7 (12.9%) had a total abdominal hysterectomy, and 11 (20.4%) had unknown or no treatment. At 6, 12, and 24months after LEEP, 8.0% (2/25), 25.0% (6/24), and 41.2% (7/17) of women had a recurrence of cervical intraepithelial neoplasia 2 or worse, respectively. ConclusionMost HIV-positive women diagnosed with ICC through screening had early-stage disease. The introduction of LEEP in-clinic increased access to treatment; however, recurrence was high, indicating the need for continued surveillance.