Recurrent Cervical Intraepithelial Neoplasia Research Articles

Treatment Failure and Recurrence of Cervical Intraepithelial Neoplasia in HIV-Infected Women

Evaluation of: Reimers LL, Sotardi S, Daniel D et al.: Outcomes after an excisional procedure for cervical intraepithelial neoplasia in HIV-infected women. Gynecol. Oncol. 119, 92-97 (2010). In a retrospective cohort study of 136 HIV-infected women who had a loop electrosurgical excision procedure (LEEP) or cone procedure for cervical intraepithelial neoplasia (CIN), Reimers et al. show that treatment failure and recurrence of CIN was common. Most recurrent CIN lesions, and those detected at treatment failure, were high-grade lesions. Both treatment failure and subsequent recurrence of CIN were found to be high in women with poorly controlled HIV, after LEEP, and those with positive cervical tissue margins following treatment. Based on these data the authors suggest that cervical conization may be superior to LEEP in the treatment of CIN in HIV-infected women.

Factors associated with recurrence of cervical intraepithelial neoplasia after conization in HIV-infected and noninfected women

To identify risk factors associated with recurrence of cervical intraepithelial neoplasia (CIN) following loop electrosurgical excision procedures in women with and without human immunodeficiency virus (HIV). A total of 33 patients with recurrent CIN and 105 without recurrence were contrasted using a nested case-control design. The patients were enrolled between 1999 and 2004. Recurrence diagnosis was established after conization, and tissues were fixed in formalin and embedded in paraffin. Polymerase chain reaction was used to detect the human papillomavirus genome (HPV DNA) types 6, 11, 16, 18, 31, 33, and 35. Statistical analysis was performed using χ² test with Yates correction and the Fisher's exact test for comparison of categorical variables. Multivariate analysis was carried out using logistic regression models. Human immunodeficiency virus infection (p = 0.001), glandular involvement (p = 0.000), and compromised margins (p = 0.02) were significantly associated with CIN recurrence. HPV DNA was positive in 57.6% of patients with CIN recurrence. High-risk HPV subtypes were detected in most cases but were not associated with recurrence (p = 0.27). In multivariate analysis, HIV infection and glandular involvement were independently associated with CIN recurrence. Human immunodeficiency virus infection and glandular involvement are associated with CIN recurrence.

Cutaneous metastases of cervical adenosquamous carcinoma

To the Editor: A 32-year-old woman with a history of cervical cancer presented with skin lesions involving her lower abdomen, hips, and groin in January 2007. The patient had undergone total abdominal hysterectomy in 2004 for recurrent cervical intraepithelial neoplasia (CIN III) and microinvasive adenosquamous cervical carcinoma. Pathologic margins were negative and the patient was well until June 2006, when she developed significant constitutional symptoms. Imaging and tumor markers were consistent with metastatic cervical cancer with extensive lymph node involvement.

Significance of human papillomavirus genotyping with high-grade cervical intraepithelial neoplasia treated by a loop electrosurgical excision procedure

This study was conducted to determine whether the human papillomavirus (HPV) genotype by the HPV DNA chip test (HDC) is predictive of residual or recurrent high-grade cervical intraepithelial neoplasia (CIN) 2-3 following a loop electrosurgical excision procedure (LEEP). Between January 2001-February 2007, 672 patients with CIN2-3 were treated by a LEEP and followed up with cytology, the hybrid capture II assay, and the HDC. A total of 37 (5.5%) patients developed a recurrence, and those who developed a recurrence tested positive for the same high-risk (HR) HPV genotype before and after the LEEP. The same HR-HPV genotype by the HDC during the follow-up had a sensitivity and negative predictive value of 100% for detecting residual/recurrent disease. Persistent HPV-16 and HPV-18 were significantly associated with recurrent CIN2-3 (P < .05). Persistent infection with the same HR-HPV genotype, especially HPV-16 and HPV-18, should be considered a risk factor for developing residual/recurrent CIN2-3.

High‐risk human papillomavirus testing for monitoring patients treated for high‐grade cervical intraepithelial neoplasia

The aim of the present study was to examine the accuracy of high-risk human papillomavirus (HR-HPV) DNA detection as a predictor of residual or recurrent cervical intraepithelial neoplasia (CIN) after treatment of high-grade CIN. Ninety-five women treated by conization and loop electrosurgical excision procedure (LEEP) for high-grade CIN were followed-up with HR-HPV DNA testing (Hybrid Capture II test, Digene Diagnostics, Gaithersburg, MD, USA) and cytology at 3, 6, 12, 18 and 24 months after treatment. The outcome of our study was to detect the presence of CIN using colposcopy-directed biopsy within 24 months after treatment. Women with recurrent or residual disease did not differ from women who were cured within clinicopathologic parameters at treatment. Pre-treatment HR-HPV testing was positive in all cases. In the recurrent pre-treatment group HR-HPV loads were significantly higher than in the group with no recurrence (1065.5 +/- 852.3 vs 527.7 +/- 669.6, P = 0.003). Residual or recurrent disease was identified in 17 patients (17.9%) during a 24-month period. A Pap smear significantly predicted disease recurrence at the first follow-up visit only. At the 6-month visit, HR-HPV testing showed 100% sensitivity and negative predictive value (NPV). When both a Pap smear and a HR-HPV test were used together, 82% sensitivity, 76% specificity and 95% NPV was noted. Performance of resection margins (odds ratio (OR) 9.8; 95% confidence interval (CI), 3.0-32.7) and post-treatment HR-HPV load >100 RLU (OR 9.3; 95% CI, 2.2-38.2) were also significant. HR-HPV testing in conjunction with Pap smear offers clear advantages over single cytology when monitoring women treated for high-grade CIN.

Posttreatment human papillomavirus testing for recurrent cervical intraepithelial neoplasia: a systematic review

We conducted a systematic review to evaluate the characteristics of human papillomavirus testing, particularly Hybrid Capture 2, in follow-up evaluations after treatment for cervical intraepithelial neoplasia for the detection of residual or recurrent cervical intraepithelial neoplasia grade >/= 2. Medline was searched for relevant studies that were published between 1992 and September 2007. Of the 1107 citations that were identified, 20 articles met the inclusion criteria. Studies that used polymerase chain reaction testing were too heterogeneous to combine. We identified 5 studies that performed both Hybrid Capture 2 and colposcopy. Pooled sensitivity for Hybrid Capture 2 was 90.7% (95% CI, 75.4-96.9%), and pooled specificity was 74.6% (95% CI, 60.4-85.0%). Pooled sensitivity for cervical cytologic testing was 76.6% (95% CI, 62.0-86.8%), and pooled specificity was 89.7% (95% CI, 22.7-99.6%). Hybrid Capture 2 testing can identify approximately 91% of women with residual or recurrent cervical intraepithelial neoplasia grade >/= 2; however, approximately 30% of women would undergo colposcopy in follow-up evaluation.

Effect of margin status on cervical intraepithelial neoplasia recurrence following LLETZ in women over 50 years

Effect of margin status on cervical intraepithelial neoplasia recurrence following LLETZ in women over 50 years

Cervical intraepithelial neoplasia recurrence after conization in HIV-positive and HIV-negative women

Objectives To evaluate the recurrence rates of cervical intraepithelial neoplasia (CIN) in a cohort of HIV-infected and noninfected women who underwent the loop electrosurgical excision procedure (LEEP). Methods A prospective cohort study of 94 HIV-positive and 107 HIV-negative women, both with CIN, treated with LEEP. The diagnosis of recurrence was established after biopsy. The Kaplan-Meier method was used for survival analysis and multivariate analyses were carried out using the Cox proportional hazards regression model. Results There was a predominance of low-grade lesions in HIV-positive compared with HIV-negative women ( P < 0.01). Recurrence was more frequent with compromised margins and glandular involvement ( P < 0.01). A multivariate analysis showed that HIV-infection, glandular involvement, and positive margins were independently associated with recurrence of lesions. Conclusions Recurrence rate of CIN in HIV-positive women was higher than in HIV-negative women. The factors associated with recurrence were HIV infection, glandular involvement, and positive margins.

Effect of margin status on cervical intraepithelial neoplasia recurrence following LLETZ in women over 50 years

To establish the effect of margin status on recurrence following large loop excision of the transformation zone (LLETZ) in women over 50 years. Prospectively collected data of women over 50 years, who underwent LLETZ for suspected cervical intraepithelial neoplasia between 1998 and 2003, were analysed. Women were followed up for up to over 6 years. District colposcopy service based at a gynae-oncology cancer centre. The main outcome measure included histologically detected recurrence. Any abnormal cytology on follow up was also documented. Prospectively collected data were analysed from the colposcopy database. Recurrence was analysed using Kaplan-Meir plots and Cox regression. Fisher's exact test was used to determine the association between margins and grade. The Kruskal-Wallis and Mann-Whitney U tests were used to compare age and duration of follow up between groups. A total of 118 women underwent LLETZ and 92 were included in the final analysis. Margins were designated as clear (n = 62), involved (n = 22) or uncertain (n = 8). Histological recurrence occurred in 12 while abnormal cytology was demonstrated in 17 women. One woman with involved margins developed cervical cancer. Individuals with clear margins were less likely to have recurrence than those with involved margins (Hazard Ratio (HR) 0.18, 95% CI: 0.06-0.59). Involved margins were more common with high-grade than low-grade lesions (P = 0.002). The data show an association between disease recurrence and the finding of involved margins in this cohort.

Predictors of persistent cytologic abnormalities after treatment of cervical intraepithelial neoplasia in Soweto, South Africa: a cohort study in a HIV high prevalence population

BackgroundIn the presence of both HIV infection and cervical intraepithelial neoplasia (CIN), the risk of cancer development despite treatment may be greater. We investigated clinical predictors of persistent cytological abnormalities in women who had had a large loop excision of the transformation zone (LLETZ).MethodsWomen with high grade squamous intraepithelial lesions or worse (HSIL), less severe abnormalities which persisted and any abnormality in women who are HIV-infected, were referred to the colposcopy clinic. HIV infection was ascertained by self-report. A LLETZ was performed on all patients with HSIL or higher on Papanicolaou (Pap) smear or colposcopy, LSIL or higher in patients who are HIV-infected, where the colposcopy is inadequate, and when there was a discrepancy between colposcopy and cytology by one or more grades. Women with abnormal follow-up smears were compared to those with normal smears. We examined the association between abnormal follow-up smears and demographic and clinical predictors using logistic regressionResultsThe median time between LLETZ and first follow-up Pap smear was rather short at 122 days. Persistent cytological abnormalities occurred in 49% of our patients after LLETZ. Predictors of persistence included the presence of disease at both margins and HIV infection. Among the latter, disease at the excision margins and CD4+ cell count were important predictors. In these women, disease at the endocervical margin, both margins, and disease only at the ectocervical margin were associated with increased odds of persistent abnormalities on follow-up cervical smear.ConclusionWe showed extremely high risk of cytological abnormality at follow-up after treatment more so in patients with incomplete excision and in the presence of immunocompromise. It remains uncertain whether recurrent CIN is a surrogate marker for invasive cervical cancer.

Risk factors, diagnosis and prognosis of cervical intraepithelial neoplasia among HIV-infected women

The prevalence of cervical intraepithelial neoplasia (CIN) is high among HIV-infected women. Decreased CD4 lymphocytes, high human immunodeficiency viral load (HIVL) and human papillomavirus (HPV) infection are risk factors for CIN. We characterized the prevalence, risk factors and prognosis of histologically-verified CIN among systematically followed HIV-infected women enrolled from a low HIV-prevalence population. The study population comprised 153 HIV-infected women followed between 1989 and 2006. The mean +/- SD duration of follow-up was 5.6 +/- 3.8 years. Demographic as well as treatment-related data were derived from medical reports. During the follow-up, 51 subjects (33%) displayed CIN (16% CIN 1 and 18% CIN 2 +), whereas 102 subjects had Pap smear results of normal cells, atypical squamous cells of uncertain significance, or signs of low-grade squamous intraepithelial lesion (LSIL) but no CIN in histological specimens from the cervix. Only one case of cancer of the uterine cervix was detected. Pap smears were reliable in screening for CIN; 75% of patients with CIN had high-grade squamous intraepithelial lesion (HSIL) or LSIL in Pap smears taken at the time of dysplasia. The incidence of CIN decreased from 12.7 to 3.5 (per 100 subjects) between 2000 and 2005 (P = 0.07). The risk of CIN was not associated with decreased levels of CD4 lymphocytes, duration of HIV infection, use of antiretroviral medication or plasma HIVL. In univariate analysis, bacterial vaginosis (BV) was associated with a significantly increased risk of CIN, whereas parity was associated with lower risk of CIN. Each delivery lowered the risk of CIN by 30% (P = 0.02). The significantly lower risk of CIN among parous women (P = 0.04) persisted in multivariate analysis. CIN was treated by means of loop electrosurgical excision procedure (LEEP), (n = 34). The recurrence rate was low; seven subjects (14%) had a recurrence of CIN during follow-up. The nadir of CD4 lymphocytes was lower (P = 0.04) and the HIVL higher (P = 0.03) among subjects with recurrence of CIN. Duration of HIV infection, use of antiretroviral medication and positive margins in LEEP specimens were indistinguishable among subjects with vs. without recurrence of CIN. The prevalence of CIN is high among systematically managed HIV-infected women. However, the incidence of CIN decreased during the 21st century. BV was associated with an increased risk of CIN whereas parous women had lower risk of CIN. However, the patients with and without CIN could not be distinguished on the basis of previously described risk factors. Regular follow-up by means of Pap smears is warranted in all HIV-infected women.

Human Papillomavirus Infection in Patients with Residual or Recurrent Cervical Intraepithelial Neoplasia

The main purpose of this longitudinal study was to evaluate the frequency of HPV infection in patients with residual or recurrent CIN. 797 consecutive patients with CIN, treated with conization, were included. In 38 patients with residual or recurrent CIN in whom reconization was performed, infection with high-risk HPV types was analyzed. Reconization was performed in 4.8% of patients. Before reconization, 21 patients (55.3%) were infected with high-risk HPV and 17 patients (44.7%) were HPV negative. Among the HPV-negative patients, two (11.8%) had CIN 1, five (29.4%) CIN 2, nine (52.9%) CIN 3 and one patient (5.9%) had microinvasive cancer of the uterine cervix. The difference in frequency of infection with high-risk HPV was not significant (chi-square 0.372; P > 0.05). On the basis of the study results it is not possible to recommend the HPV test as the only method of detection of residual or recurrent CIN after conization.

Recurrence of cervical intraepithelial neoplasia grades 2 or 3 in HIV-infected women treated by large loop excision of the transformation zone (LLETZ).

Women infected by HIV are more likely to have cervical cancer and its precursors. Treatment of the precursor lesions can prevent this neoplasia. The aim of this study was to assess the likelihood of recurrent cervical intraepithelial neoplasia grades 2 or 3 (CIN 2-3) in HIV-infected women, compared with HIV-negative women, all treated by large loop excision of the transformation zone (LLETZ). A cohort study in Instituto Fernandes Figueira, Fundação Oswaldo Cruz (IFF-Fiocruz), Rio de Janeiro. 55 HIV-positive and 212 HIV-negative women were followed up after LLETZ for CIN 2-3 (range: 6-133 months). The incidence of recurrent CIN 2-3 was 30.06/10,000 woman-months in the HIV-positive group and 4.88/10,000 woman-months in the HIV-negative group (relative risk, RR = 6.16; 95% confidence interval, CI: 2.07-18.34). The likelihood of recurrence reached 26% at the 62nd month of follow-up among the HIV-positive women, and remained stable at almost 0.6% at the 93rd month of follow-up among the HIV-negative women. We were unable to demonstrate other prognostic factors relating to CIN recurrence, but the use of highly active antiretroviral therapy (HAART) may decrease the risk of this occurrence among HIV patients. After LLETZ there is a higher risk of recurrence of CIN 2-3 among HIV-positive women than among HIV-negative women. This higher risk was not influenced by margin status or grade of cervical disease treated. The use of HAART may decrease the risk of this occurrence in HIV patients.

Aberrant Promoter Methylation Can be Useful as a Marker of Recurrent Disease in Patients with Cervical Intraepithelial Neoplasia Grade III

Although studies of risk factor profiles have been conducted to identify biological markers to predict the natural history of cervical intraepithelial neoplasia (CIN) grade III, there is not sufficient information to support the routine clinical use of any biomarker. The purpose of this study was to examine aberrant promoter methylation, which is implicated in cancer development and progression, in CIN III lesions in order to identify markers associated with more aggressive biological behavior that could be used to recognize women who are at higher risk of recurrence. We used methylation-specific polymerase chain reaction to analyze promoter hypermethylation of 8 genes (p16, RARbeta, GSTP1, MGMT, p14, TIMP3, E-cad and DAPk) in 33 uterine cervix cones with CIN III that were also submitted to human papillomavirus (HPV) genotyping. All 33 patients in this study had been clinically followed after conization with Papanicolaou smears, colposcopy, and biopsy when indicated, every 6 months during 5 years. Of the 33 patients, 12 (36%) underwent immediate hysterectomy after conization for having compromised cone margins, 14 (43%) have not relapsed, and 7 (21%) presented CIN relapse. The frequency of HPV infection in this group was 97% and no significant difference between the groups was observed. HPV of high oncogenic risk was present in 29 (87.9%) cases; HPV 16 was the most frequent (69.7%), while HPV 18 was found in 33.3%; however, it was associated with HPV 16 in 15.1%. Concomitant infection by HPV 6/11 was detected in 21.2% (15.1% with HPV 16 and 6.1 with HPV 18). 85.7% (6/7) of patients with recurrence had HPV 18 vs 0% (0/14) of patients without recurrence (P = 0.0001). At least 1 of the 8 genes was found hypermethylated in all samples. Concomitant hypermethylation of several genes was frequently found. However, CIN relapse was only seen in the cases with hypermethylation of 3 or more of the 8 genes studied (P = 0.0039). We suggest that aberrant promoter methylation may play a role and may serve as a useful biomarker in the recurrence of CIN.

Increased Sensitivity of Radiated Murine Cervical Cancer Tumors to E7 Subunit Vaccine–driven CTL-mediated Killing Induces Synergistic Anti-tumor Activity

The development of therapeutic vaccines has important implications for the treatment of cancer patients. Here we investigate whether human papillomavirus (HPV) E7 subunit vaccines can enhance tumor radioresponse using an established cervical cancer animal model. Radiation plus E7 subunit vaccines improved complete response, cure, and recurrence rates of tumors dramatically compared with single therapy alone. In particular, both components of the E7 subunit vaccines (E7 protein and CpG-oligodeoxynucleotide) were required for the induction of antigen (Ag)-specific cytotoxic T-lymphocyte (CTL) responses and for therapeutic synergy with radiotherapy. Moreover, with combined therapy the radiation dose could be reduced by 16 Gy to achieve an equivalent anti-tumor efficacy to radiation treatment alone. This therapeutic synergy was found to be mediated by CD8(+) CTLs and was concomitant with histological changes (presence of apoptotic bodies and multinucleated giant cells; heavy infiltration of lymphocytes), as determined by in vivo T-cell depletion and histological analysis. Finally, phenotypic changes of radiated tumors and their increased sensitivity to CTL-mediated killing appeared to be responsible for therapeutic synergy. These results show that E7 subunit vaccines act as a potent enhancer of tumor radioresponse and that this is mediated by increased sensitivity of radiated tumors to CTL-mediated killing. This study further suggests that E7-targeted therapeutic vaccines have the potential to improve radiotherapy in patients with cervical cancer.

Persistence of human papillomavirus as a predictor for treatment failure after loop electrosurgical excision procedure

We aimed to investigate whether postconization human papillomavirus (HPV) DNA testing can predict treatment failure and improve the accuracy of conventional follow-up in women with high-grade cervical intraepithelial neoplasia (CIN). Between March 2001 and October 2005, 120 patients with confirmed CIN 2 or 3 were treated with loop electrosurgical excision procedure (LEEP) and were enrolled. Six patients were lost to the follow-up. Postconization follow-up was performed at every 3-6 months during the first year and then annually. Specimens were tested for the presence of HPV, using the Hybrid Capture 2 (Digene Co, Gaithersburg, MD) and HPV DNA chip (Mygene Co, Seoul, Korea) test. Persistent HPV infection was defined as persistently (two times or more) positive HPV tests with the same HPV subtype(s) at initial diagnosis. Twenty-two (19.3%) patients showed treatment failure after conization. The only significant risk factor for redevelopment of CIN after conization was persistence of the same HPV subtype (P < 0.0001). And women with recurrent or residual CIN had higher HPV load during the 6-month follow-up postconization. In conclusion, the persistence of the same HPV subtype after LEEP conization was an important predictor of treatment failure. The follow-up protocol after conization of CIN should include both cervical cytology and HPV test, and HPV DNA chip test is needed to detect a persistent HPV infection.

Prediction of recurrence after treatment for high‐grade cervical intraepithelial neoplasia: the role of human papillomavirus testing and age at conisation

The aim of this study was to examine the accuracy of the presence of high-risk human papillomavirus (HR-HPV) DNA (HR-HPV DNA test) postconisation as prediction of recurrent or residual cervical intraepithelial neoplasia (CIN) after treatment of high-grade cervical intraepithelial lesions (CIN2+) in a prospective study and to compare this with follow-up cytology and the marginal status of the excised tissue. Prospective follow-up study. Unselected women presenting at colposcopy clinic of University Hospital Gasthuisberg, Leuven. Seventy-two women treated with conisation for CIN2 or CIN3. Women were followed by HR-HPV DNA test (Hybrid Capture II test of Digene) every 3 to 6 months. The same vial was used for cytology and the HR-HPV DNA test (SurePath). All women were further followed by colposcopy and cytology for 24 months at 6-month intervals. The outcome of the study was presence of >CIN2, proven with colposcopy-directed biopsy occurring within 24 months after treatment. HR-HPV status was correlated with recurrent or residual CIN2+. Sensitivity, specificity, predictive values and diagnostic odds ratios to predict treatment failure or cure were computed for HR-HPV testing, marginal status and follow-up cytology. HR-HPV status was also correlated with section margins postconisation and with the first cervical smear. In 6 of the 72 treated women (8%), residual or recurrent CIN occurred. Women with recurrence were significantly older than women without a recurrence (51.5 +/- 9.6 versus 39.8 +/- 12.2 years, P= 0.007). All six women with recurrence were HR-HPV positive, four had a positive follow-up smear (>or=atypical squamous cells of uncertain significance = ASCUS+) and only two had involved section margins. Among the 66 cured women, 15 were HR-HPV positive, 6 had an abnormal smear and 12 had positive section margins. Sensitivity of cytology, positive section margins and HR-HPV DNA positivity was 66.7, 33.3 and 100% to predict treatment failure. Specificity of the three tests was, respectively, 90.9, 81.8 and 77.3%. Women with HR-HPV DNA at 3 to 6 months showed recurrent or residual CIN in 15% (2/13) if they had normal follow-up Pap smears and in 50% (4/8) if they had abnormal Pap smears. Margin status was not statistically significantly associated with human papillomavirus status. Persistence or clearance of HR-HPV DNA is an early valid prognostic marker of failure or cure after treatment for CIN2+ and is more accurate than cytology or section margin status at the time of conisation. The absence of HR-HPV DNA has a 100% negative predictive value. Higher age at conisation may be a previously unrecognised risk factor for recurrence.

Is colposcopy needed following laser ablation for dysplasia?

To evaluate the effectiveness of cytology and colposcopy in the follow up of women treated by laser CO(2) ablation for cervical intraepithelial neoplasia (CIN). A retrospective analysis of 1784 patients with CIN treated with laser CO(2) ablation from 1998 to 2003 at the Royal Women's Hospital, Melbourne. Data were collected prospectively in a computerised colposcopy database utilised in the Dysplasia Unit. There was equal distribution in the study population treated for low-grade intraepithelial neoplasia (LSIL) and high-grade intraepithelial neoplasia (HSIL), with no significant age difference in both groups (mean 27.6 years). The success rate of treatment of LSIL (94%) was similar to that of HSIL (92%). Fifty-seven per cent of all failures occurred within the first year of treatment. Colposcopy was more sensitive in detecting intraepithelial neoplasia (SIL) than cytology, whereas cytology was more specific. No case of cancer was diagnosed on follow up. CO(2) laser ablation was equally effective in treating different grades of CIN. There is a continuing incidence of recurrent CIN, even up to five years after initial treatment, which suggests that it is necessary for patients to adhere to long-term follow up. The combination of cytology and colposcopic assessment is essential for surveillance of SIL in the initial two years after treatment.

The recurrence of cervical intraepithelial neoplasia in HIV-positive women: a review of the literature

The objective of this study was to assess the available evidence on the outcome of cervical intraepithelial neoplasia (CIN) in HIV-positive women after conization. We performed a literature search of Medline and Cochrane libraries to locate published articles reporting about the rate of recurrence of CIN after excisional treatment in patients with negative surgical margins. Out of 15 articles, five studies reported recurrence rate of CIN in margin negative patients. The recurrence rate of CIN after conization in HIV-infected women ranges from 20% to 75%. No conclusions can be drawn about the impact of CD4 cell counts on the recurrence rate. Available evidence suggests that standard excisional treatments for CIN are associated with high rates of recurrence in HIV-positive women. Despite the fact that the evidence is limited because of the few number of eligible studies, this issue should be considered in the management of HIV-positive patient with CIN.

Chapter 9: Clinical applications of HPV testing: A summary of meta-analyses

Background More than ever, clinicians need regularly updated reviews given the continuously increasing amount of new information regarding innovative cervical cancer prevention methods. Material and methods A summary is given from recently published meta-analyses on three possible clinical applications of human papillomavirus (HPV)-DNA testing: triage of women with equivocal or low-grade cytological abnormalities; prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN) lesions, and last not but not least, primary screening for cervical cancer and pre-cancer. Results Consistent evidence is available indicating that HPV-triage with the Hybrid Capture-2 assay (HC2) is more accurate (significantly higher sensitivity, similar specificity) than repeat cytology to triage women with equivocal Pap smear results. When triaging women with low-grade squamous intraepithelial lesions (LSIL), a reflex HC2 test does not show a significantly higher sensitivity, but a significantly lower specificity compared to a repeat Pap smear. After treatment of cervical lesions, HPV testing easily detects (with higher sensitivity and not lower specificity) residual or recurrent CIN than follow-up cytology. Primary screening with HC2 generally detects 23% (95% confidence interval, CI: 13–23%) more CIN-2, CIN-3, or cancer compared to cytology at cut-off atypical squamous cells of undetermined significance (ASCUS) or LSIL, but is 6% (95% CI: 4–8%) less specific. By combined HPV and cytology screening, a further 4% (95% CI: 3–5%) more CIN-3 lesions can be identified but at the expense of a 7% (95% CI: 5–9%) loss in specificity, in comparison with isolated HC2 screening. Conclusions Sufficient evidence exists to recommend HPV testing in triage of women with atypical cytology and in surveillance after treatment of CIN lesions. In the United States, recently reviewed knowledge has resulted in the approval of combined cytology and HC2 primary screening in women older than 30 years. However, in Europe, cytology-based screening still remains the standard screening method. The European screening policy will be reviewed based on the longitudinal results of randomised population trials which are currently underway.