Absence of dysplasia in the excised cervix by a loop electrosurgical excision procedure in the treatment of cervical intraepithelial neoplasia

Objective

Absence of dysplasia in the excised specimen following loop electrosurgical excision procedure (LEEP) for treatment of cervical intraepithelial neoplasia (CIN) 2/3 is an occasional finding of uncertain clinical significance. We evaluated several factors including age, liquid-based Pap (LBP) test, human papillomavirus (HPV) load before treatment, and HPV typing as predictors for absence of dysplasia. Absence of dysplasia in LEEP specimens was analyzed in terms of factors for recurrent disease after LEEP conization

Methods

In total, 192 women (mean age, 39.3±8.4 years; range, 24 to 70 years) with biopsy-proven CIN 2/3 were treated by LEEP conization. Age, LBP test, histological grade, HPV load, and HPV DNA typing were evaluated as possible predictors of the absence of residual dysplasia or recurrent disease.

Results

Of the LEEP specimens, 34 (17.7%) showed no dysplasia in preoperative biopsies from patients with proven CIN 2/3. Low HPV load (<100 relative light units [RLU]) was significantly related to the absence of dysplasia in LEEP specimens, using logistic regression. Margin involvement and high HPV load (≥400 RLU) were significant factors for recurrence.

Conclusion

Absence of dysplasia in LEEP specimens occurred in 17.7% of our specimens. Prediction of the absence of dysplasia in LEEP specimens was associated with low HPV load. Residual/recurrent disease after LEEP was associated with a positive resection margin and high viral load, and was not associated with absence of dysplasia in LEEP specimens. Even if there is no dysplasia in conization specimens, close follow-up for residual/recurrent disease is needed.     

A human papillomavirus (HPV)-16 or HPV-18 genotype is a reliable predictor of residual disease in a subsequent hysterectomy following a loop electrosurgical excision procedure for cervical intraepithelial neoplasia 3

Objective

This study was conducted using the human papillomavirus (HPV) DNA chip test (HDC), in order to determine whether the HPV genotype is a predictor of residual disease in a subsequent hysterectomy following a loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia (CIN) 3.

Methods

Between January 2002 and February 2015, a total of 189 patients who underwent a hysterectomy within 6 months of LEEP caused by CIN 3 were included in this study. We analyzed their epidemiological data, pathological parameters, high-risk HPV (HR-HPV) load as measured by the hybrid capture II assay, and HR-HPV genotype as measured by the HDC. A logistic regression model was used to analyze the relationship between covariates and the probability of residual disease in subsequent hysterectomy specimens.

Results

Of the 189 patients, 92 (48.7%) had residual disease in the hysterectomy specimen, CIN 2 in seven patients, CIN 3 in 79 patients, IA1 cancer in five patients, and IA2 cancer in one patient. Using multivariate analysis, the results were as follows: cone margin positivity (odds ratio [OR], 2.43; 95% CI, 1.18 to 5.29; p<0.05), HPV viral load ≥220 relative light unit (OR, 2.98; 95% CI, 1.38 to 6.43; p<0.01), positive endocervical cytology (OR, 8.97; 95% CI, 3.81 to 21.13; p<0.001), and HPV-16 or HPV-18 positivity (OR, 9.07; 95% CI, 3.86 to 21.30; p<0.001).

Conclusion

The HPV-16 or HPV-18 genotype is a reliable predictive factor of residual disease in a subsequent hysterectomy following a LEEP for CIN 3.     

Factors associated with HPV persistence after conization in patients with negative margins

Objective

The clearance rate of human papillomavirus (HPV) after conization is generally high, although some HPV infections persist. We investigated the factors that affect the clearance of HPV after conization in patients with negative margins.

Methods

We retrospectively analyzed 77 patients (mean age 39.9 years, range 25 to 51 years) with CIN 2/3 who underwent loop electrosurgical excision procedure (LEEP) conization with negative margins. All patients had a Pap smear and high-risk (HR) HPV testing using Hybrid Capture II system and HPV DNA chip before conization. We used≥1 relative light units (RLUs) as the cutoff for persistence of HPV after conization.

Results

High-risk HPV was detected in 73 of 77 (94.8%) patients before conization. At the 6-months follow-up, the high-risk HPV was eliminated in 60 of 73 (82.2%) patients. The HPV persistence rate after conization was 17.8% (13/73). Univariate analysis showed that persistent HPV infection after conization with negative margins was more likely to occur when the pretreatment viral load was high (RLU/positive control >100 (p=0.027) and the HPV was type 16 (p=0.021). Logistic regression analysis showed that preoperative HPV type 16 infection was the only significant independent factor (p=0.021) for HPV persistence out of age, cytology, punch biopsy histology, HPV viral load, and conization histology.

Conclusion

Conization effectively removes HR-HPV infection. HPV type 16 infection before conization was significantly related to HR-HPV persistence after conization with negative margins. Therefore, patients with HPV 16 infection before conization need to be followed closely.     

Triaging borderline/mild dyskaryotic Pap cytology with p16/Ki-67 dual-stained cytology testing: cross-sectional and longitudinal outcome study

Background:

Women with borderline/mildly dyskaryotic (BMD) cytology smears are currently followed up with repeat testing at 6 and 18 months. The objective of this study is to analyse the cross-sectional and longitudinal performance of p16/Ki-67 dual-stained cytology for the detection of cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) and CIN2+ in women with BMD, and to compare the results with baseline human papillomavirus (HPV) testing.

Methods:

Conventional Pap cytology specimens of 256 women with BMD were dual stained for p16/Ki-67 retrospectively, and compared with baseline HPV results and long-term follow-up results.

Results:

p16/Ki-67 dual-stained cytology showed a sensitivity of 100%, a specificity of 64.4% and a negative predictive value (NPV) of 100.% for CIN3+. Human papillomavirus testing demonstrated similar sensitivity (96.3%), and NPV (99.1%), but a significantly lower specificity (57.6% P=0.024) for CIN3+. Sensitivity, specificity and NPV for CIN2+ of dual-stained cytology were 89.7%, 73.1% and 95.1%, respectively, which was similar when compared with HPV testing. Dual-stained cytology showed a significant lower referral rate than HPV testing (43.6% vs 49.1% P=0.043). During long-term follow-up, no CIN3+ lesions developed in HPV-positive, dual-stained negative women.

Conclusions:

Comparable sensitivity and NPV of dual-stained cytology for CIN3+, combined with a significantly higher specificity, makes p16/Ki-67 dual-stained cytology a viable alternative to HPV testing for triaging BMD.     

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

Objective

We 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).

Methods

Source 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.

Results

The 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).

Conclusion

Our 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.     

Association between bacterial vaginosis and cervical intraepithelial neoplasia

Objective

The aim of this study was to determine whether the presence of bacterial vaginosis (BV) is associated with cervical intraepithelial neoplasia (CIN) and human papilloma virus (HPV) infection.

Methods

A total of 588 women who had abnormal Pap smears and had finally undergone loop electrosurgical excision procedure (LEEP) in our institute from September 2002 to May 2006 were selected. The screening tests for BV were done in 552 of the 588, and BV was diagnosed if three of the following four findings were satisfied: presence of abnormal discharge, vaginal pH>4.5, presence of clue cells, positive amine or whiff test. Five hundred and five patients had HPV typing tests by the HPV DNA chip. Forty two patients diagnosed with invasive cancer were excluded from this study. CIN was subdivided into low-grade CIN (CIN I) and high-grade CIN (CIN II/III) groups.

Results

There was no statistically significant difference in patient characteristics between BV-present and BV-absent group. The incidence of CIN was significantly higher in the BV-present group (p=0.043), however, no statistical significance of BV on CIN was observed on multivariate analysis. HPV infection showed no significant relationship with BV. BV with or without HPV infection did not influence the incidence of CIN, regardless of the severity.

Conclusion

There was significant correlation between BV and the presence of CIN, regardless of the severity of CIN. In addition, there was no significant association between the presence of BV and HPV infection.     

Pap Smear Combined with HPV Testing: A Reasonable Tool for Women with High-grade Cervical Intraepithelial Neoplasia Treated by LEEP

Background: To evaluate HPV testing by Hybrid Capture II (HCII) in conjunction with cytology in detectingthe residual/recurrence disease after treatment of high-grade cervical intraepithelial neoplasia (CIN II-III) withloop electrosurgical excision procedure (LEEP). Materials and Methods: A retrospective review of 158 patientswith histologically confirmed CIN II-III who underwent LEEP between January 2011 and October 2012 wasconducted. Post-treatment control was scheduled at the 3rd, 6th, 12th and 18th month. All patients were followedup by Pap smear and HR-HPV genotype and viral load testing. Results: Pre-treatment, HR-HPV DNA, wasdetected in all specimens of the patients. At follow-up, 25 patients were diagnosed as the residual/recurrent diseaseduring the FU visit, among whom, 16 patients with positive margin: 13 patients (52%) with HR-HPV DNA+/cytology+, 2 patients (8%) with HR-HPV DNA+/cytology-, 1 patient (4%) with cytology+/ HR-HPV DNA-; 9patients with clean margin – 5 patients (55.6%) with HR-HPV DNA+/cytology+; 2 patients (22.2%) with HRHPVDNA+/cytology-, 2 patients (22.2%) with cytology+/ HR-HPV DNA-. None of them persisting HR-HPVDNA-/cytology- with positive or negative margin was identified as the residual/recurrent disease. The majorityof residual/recurrent disease was detected at the 12th and 18th month FU, and there was almost no differencein the sensitivity and negative predictive value (NPV) between at the 3rd month and the 6th month FU visits. 14residual/recurrence disease (14/46:30.4%) had pre-treatment high viral load (>5 000 RUL/PC) and 11 (11/112,9.8%) with pre-treatment low viral load, P<0.05. Conclusions: (1) The persistence HR-HPV DNA is the rootcause of the residual/recurrent disease for the women treated for high-grade CIN; the pre-treatment viral loadand margin can be seen as the predictor. (2) The FU visit beginning at the 6th month post-treatment and lastingat least 24 months with the combination of cytology and HPV testing. (3) Patients with high pre-treatment HPVload, which is considered as one risk of developing the residual/recurrent disease, should be paid more attention(especially above 500RUL/PC) to by clinicians.     

The accuracy of cervical cancer and cervical intraepithelial neoplasia diagnosis with loop electrosurgical excisional procedure under colposcopic vision

Objective

The colposcopic vision guided loop electrosurgical excisional procedure (LEEP) was studied for the effective diagnosis of cervical cancer and cervical intraepithelial neoplasia (CIN).

Methods

A total of 199 patients participated in this study. Individual cases were from gynecologic outpatients at Thammasat University Hospital, Thailand. These had diagnoses for CIN and were selected for treatment with colposcopic guided LEEP. The average age of patients in this study was 45. Menopausal women represented 31%, (61/199) of the patients. The most frequently found Pap smear result among these women (44%, 88/199), was that of high-grade squamous intraepithelial lesion. The next most frequent Pap smear result (32%, 64/199) was low-grade squamous intraepithelial lesion. Patients'' medical records and outcomes were evaluated for consistency of pathological examination between colposcopic directed biopsy and LEEP. Discrepancies between initial diagnosis and the final diagnosis were also analyzed.

Results

The colposcopic guided LEEP accurately determined 100% of the cervical cancer cases and 84.8 % of the high-grade squamous intraepithelial lesion cases. Involvement of the ectocervical or endocervical margin regions was found to be 5% and 10% respectively, in this study. Excessive bleeding complication, either during the excision and/or postoperative recovery was found in 3% and 6% of cases, respectively.

Conclusion

LEEP under colposcopic vision is a recommended technique for ambulatory management of precancerous lesion and early diagnosis of cervical cancer. This technique significantly reduces rate of positive ectocervical cone margin involvement.     

hr-HPV testing in the follow-up of women with cytological abnormalities and negative colposcopy

Background:

The follow-up after abnormal Pap smear and negative colposcopy is not clearly defined. This study aimed at investigating the role of hr-HPV testing in the management of abnormal Pap test and negative colposcopy for Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+).

Methods:

The study enroled 1029 women with abnormal screening cytology (years 2006–2010) and negative colposcopy for CIN2+, which subsequently performed a hr-HPV test. Incident CIN2+ lesions were identified through linkage with cancer registry, hospital discharge records, neoplastic pathology reports and the archive of screening programme (2006–2011).

Results:

During the follow-up, the cohort developed 133 CIN2+ lesions; only one among hr-HPV-negative women. The probability of developing CIN2+ on follow-up time was 0.44% (95% confidence interval (CI) 0.1–3.1) and 41.8% (95% CI 31.8–53.5) for hr-HPV-negative women and hr-HPV-positive women, respectively. A woman with a positive hr-HPV test had about 105 times higher probability of developing a CIN2+ lesion than a woman with a negative hr-HPV test (hazard ratio (HR)=104.5, 95% CI 14.5–755.1), adjusted for index Pap test result, age and cervix squamocolumnar junction visualisation.

Conclusion:

Our results confirm that hr-HPV testing is able to select the real group of women at risk of developing CIN2+ lesions in the follow-up of abnormal cytology and first negative colposcopy.     

Expression of the p16INK4a and Ki-67 in relation to the grade of cervical intraepithelial neoplasia and high-risk human papillomavirus infection

Objective

The purposes of this study were to evaluate the expression of p16^INK4a (referred as to p16) and Ki-67 in cervical intraepithelial neoplasia (CIN), and the correlation between high-risk human papillomavirus (HPV) infection and the above biomarkers.

Methods

We analyzed 31 patients who were diagnosed with CIN at Kwandong University Myongji Hospital from October 2006 to September 2007. CIN specimens (CIN1, 12; CIN2, 6; CIN3, 13) were obtained by colposcopy-directed biopsy (CDB) or loop electrical excision procedure (LEEP). The expressions of p16 and Ki-67 were evaluated by immunohistochemical methods with antibodies to p16 and Ki67. The immunohistochemical staining results were classified into four grades: 0, 1, 2 and 3. HPV genotyping or Hybrid Capture-II test was used to detect high-risk HPV.

Results

The expression of p16 (p<0.001) and Ki-67 (p=0.003) were positively associated with CIN grade. p16 expressions increased significantly with high-risk HPV infection (p=0.014), especially HPV type 16 and 58. Ki-67 expression was not related with high-risk HPV. There was positive correlation between the expression of the p16 and Ki-67 (p=0.007).

Conclusion

CIN grade were positively related to the expression of p16 and Ki-67. p16 expressions of high-risk HPV specimens significantly increased more than Ki-67. Therefore, in the diagnosis of CIN and high-risk HPV infection, p16 can be a useful biomarker.     

End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine in adult women 24-45 years of age

Background:

Previous analyses from a randomised trial in women aged 24–45 years have shown the quadrivalent human papillomavirus (qHPV) vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN), and external genital lesions (EGLs) related to HPV 6/11/16/18. In this report, we present end-of-study efficacy, safety, and immunogenicity data with a median follow-up time of 4.0 years.

Methods:

We enrolled 3819 24–45-year-old women with no history of cervical disease or genital warts in the past 5 years. Women received quadrivalent vaccine or placebo at day 1, and at months 2 and 6. Ascertainment of CIN/EGL was accomplished through Pap testing, genital inspection, and cervicovaginal sampling (every 6 months). The main analysis was conducted in a per-protocol efficacy population (that received three doses, was naive to the relevant HPV types at day 1, and remained free of infection through month 7). Efficacy was also estimated in other naive and non-naive populations.

Results:

Vaccine efficacy against the combined incidence of persistent infection, CIN/EGL related to HPV6/11/16/18 in the per-protocol population was 88.7% (95% CI: 78.1, 94.8). Efficacy for women who were seropositive and DNA negative for the relevant vaccine HPV type at the time of enrolment who received at least 1 dose was 66.9% (95% CI: 4.3, 90.6). At month 48, 91.5, 92.0, 97.4, and 47.9% of vaccinated women were seropositive to HPV 6/11/16/18, respectively. No serious vaccine-related adverse experiences were reported.

Conclusions:

The qHPV vaccine demonstrated high efficacy, immunogenicity, and acceptable safety in women aged 24–45 years, regardless of previous exposure to HPV vaccine type.     

Type- and age-specific distribution of human papillomavirus in women attending cervical cancer screening in Finland

Background:

Large-scale data on type-specific HPV prevalences and disease burden are needed to monitor the impact of HPV vaccination and to plan for HPV-based cervical screening.

Methods:

33 043 women (aged 25–65) were screened for HPV by a Hybrid Capture 2 (HC2) in a population-based programme. HPV-positive women (n=2574) were triaged by cytology and HPV genotyped using PCR-Luminex. Type-specific prevalence of HPV infection and its correlation to findings in cytology triage and histology as well as Population Attributable Fractions for a referral to colposcopy and findings in histology were calculated.

Results:

Among HC2-positive women, 61.5% had normal, 23.1% had ASC-US and 15.5% had LSIL or more severe (LSIL+) results in cytology. Out of HC2-positive samples, 57% contained the 13 Group 1/2A HPV types, which were targeted by the HC2, 15% contained Group 2B types, 8.5% Group 3 types and 30% were found to be negative in HPV genotyping. The proportion of samples positive for HPV by the HC2, but negative in HPV genotyping increased with age and decreased with increasing cytological abnormality. The most frequent types were HPV 16 (0.9% of screened women and 12.1% of the HC2-positive women), HPV 31 (0.7% and 8.9%, respectively) and HPV 52 (0.5% and 6.3%, respectively). The prevalence of Group 1/2A HPV types increased with increasing CIN grade and attributed 78.3% (95% CI 53.4–89.9) of the CIN 3+ lesions, while HPV 16 attributed 55.8% (40.0–67.5) of them.

Conclusion:

The type-specific prevalence of HPV were slightly lower than the average in international meta-analyses. Genotyping for HPV 16 better identified women with CIN 3+ than cytology triage at the threshold of LSIL+. The high proportion of women that were HC2-positive but HPV-negative in genotyping suggests that HPV genotyping may be useful also for validation of results in HPV screening. The large-scale HPV genotyping data were found to be directly useful for planning further preventive efforts for cervical cancer.     

Primary cervical cancer screening with HPV testing compared with liquid-based cytology: results of round 1 of a randomised controlled trial �C the HPV FOCAL Study

Background:

Round 1 data of human papillomavirus (HPV) FOCAL, a three-arm, randomised trial, which aims to establish the efficacy of HPV DNA testing as a primary screen for cervical cancer, are presented.

Methods:

The three arms are: Control arm – liquid based cytology with atypical squamous cells of unknown significance (ASC-US) triage with hrHPV testing; Intervention Arm – hrHPV at entry with liquid-based cytology (LBC) triage of hrHPV positives, with exit screen at 4 years; Safety check arm – hrHPV at entry with LBC triage of hrHPV positives with exit screen at 2 years.

Results:

A total of 6154 women were randomised to the control arm and 12 494 to the HPV arms (intervention and safety check). In the HPV arm, the baseline cervical intraepithelial neoplasia (CIN)2+ and CIN3+ rate was 9.2/1000 (95%CI; 7.4, 10.9) and 4.8/1000 (95%CI; 3.6, 6.1), which increased to 16.1/1000 (95%CI 13.2, 18.9) for CIN2+ and to 8.0/1000 (95%CI; 5.9, 10.0) for CIN3+ after subsequent screening of HPV-DNA-positive/cytology-negative women. Detection rate in the control arm remained unchanged after subsequent screening of ASC-US-positive/hrHPV DNA-negative women at 11.0/1000 for CIN2+ and 5.0/1000 for CIN3+.

Conclusion:

After subsequent screening of women who were either hrHPV positive/cytology negative or ASC-US positive/HPV negative, women randomised to the HPV arms had increased CIN2+ detection compared with women randomised to the cytology arm.     

Incomplete follow-up of positive HPV tests: overview of randomised controlled trials on primary cervical screening

Background:

It has been suggested that adjustment for incomplete compliance with follow-up in women with positive human papillomavirus (HPV) tests would be appropriate for estimating the true sensitivity of cervical screening with HPV testing. We assessed the compliance and its impact on ⩾CIN3 detection in all eight randomised controlled trials (RCT) with published baseline-round data.

Methods:

We extracted data on recommended follow-up procedures, follow-up compliance, and ⩾CIN3 detection for both arms of each RCT, and assessed their correlation.

Results:

Compliance with a direct referral for colposcopy was around 90% in all RCTs, whereas compliance with repeated testing among HPV-positive/cytology-negative women was around 60% in three RCTs and 73% in one RCT. Detection of ⩾CIN3 was significantly increased in two out of six RCTs with reported data. The correlation between compliance with follow-up in HPV-positive women and relative ⩾CIN3 detection was 0.48 (P=0.33).

Conclusion:

There is at present scant evidence to support the view that the measured sensitivity of HPV screening is a simple reflection of compliance with follow-up. Adjustment of measured cervical intraepithelial neoplasia detection on the basis of compliance data may not always be justifiable, and if adjustment is made, it should be used very judiciously.     

Short-time repeat high-risk HPV testing by self-sampling for screening of cervical cancer

Background:

Testing for high-risk human papillomavirus (HPV) in primary screening for cervical cancer is considered more sensitive, but less specific, in comparison with Pap-smear cytology. Women with persistent HPV infections have a higher risk of developing cervical intraepithelial neoplasia 2+ (CIN2+) lesions. This study was performed to evaluate the gain in specificity for detection of histologically confirmed CIN2+ lesions achieved by short-time repeat testing for high-risk HPV in women aged 30–65 years, with the primary sample for HPV analysis taken by self-sampling.

Methods:

A total of 8000 women in Uppsala County, aged 30–65 years, who had not attended organised screening for 6 years or longer, were offered self-sampling of vaginal fluid at home and the samples sent for HPV typing. Of these, 8% (669) were not possible to contact or had performed hysterectomy. Women positive for high-risk HPV in the self-sampling test were invited for a follow-up HPV test and a cervical biopsy on average 3 months after the initial HPV test.

Results:

In all, 39% (2850/7331) of invited women chose to perform self-sampling of vaginal fluid at home. High-risk HPV infection was found in 6.6% (188) of the women. In all, 89% of the women testing HPV positive performed a follow-up examination, on average 2.7 months, after the first test and 59% of these women were HPV positive in the follow-up test. The prevalence of CIN2+ lesions in women with an initial HPV-positive test was 23% (95% CI 18–30%) and in women with two consecutive HPV-positive tests was 41% (95% CI 31–51%). In women with two positive HPV tests, the prevalence of CIN2+ lesions varied from 49% in women at age 30–39 years to 24% in women at age 50–65 years. Short-time repeat HPV testing increased the specificity for detection of CIN2+ lesions from about 94.2% to 97.8%. The most prevalent HPV types were HPV16 (32%), followed by HPV18/45 (19%) and HPV 33/52/58 (19%).

Conclusion:

The short-time persistence of high-risk HPV infection in this age group was about 60%. Repeat testing for high-risk HPV using self-sampling of vaginal fluid can be used to increase the specificity in the screening for cervical cancer in women aged 30–65 years.     

The clinical performance of APTIMA human papillomavirus and Hybrid Capture 2 assays in the triage of lesser abnormal cervical cytologies

Objective

This study was performed to evaluate the clinical performance of APTIMA human papillomavirus (AHPV) assay and Hybrid Capture 2 (HC2) assay in screening for cervical disease, especially in women with atypical squamous cell of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL).

Methods

A total of 411 women diagnosed with ASC-US or LSIL were referred and further triaged by HC2 test. Prior to colposcopy, liquid-based cytology specimens were collected for the AHPV assay. Sensitivity and specificity were established based on the histological findings of cervical intraepithelial neoplasia (CIN).

Results

In all 411 subjects, the positive detection rate of AHPV assay was 70.8% (95% confidence interval [CI], 66.4 to 75.2), which was significantly lower than the positive detection rate of 94.9% obtained using HC2 test (95% CI, 92.3 to 96.8). Only one CIN 3-positive case was detected among the 120 AHPV-negative women, which was then confirmed by Pap smear test to be LSIL. The sensitivities of AHPV and HC2 for CIN 3 were similar (94.1% and 100%, respectively). However, AHPV showed a significantly higher specificity than HC2 test (30.2% and 5.3%, respectively; p<0.001).

Conclusion

AHPV assay is effective in identifying CIN 3-positive cases because of its high specificity and lower false-negative rate. The use of AHPV for the triage of ASC-US and LSIL might help to reduce the referral rate of colposcopy during cervical cancer screening.     

Prevalence and determinants of human papillomavirus infection and cervical lesions in HIV-positive women in Kenya

Background:

We assessed the association of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) with various characteristics, CD4 count and use of combination antiretroviral therapy (cART) among HIV-positive women.

Methods:

Cross-sectional study of 498 HIV-positive women who underwent HPV PCR-based testing, cytology, and systematic cervical biopsy.

Results:

In all, 68.7% of women were HPV-positive, 52.6% had high-risk (hr) HPV, and 40.2% multiple type infections. High-risk human papillomavirus-positivity did not vary significantly by age but it was negatively associated with education level. The most frequent types in 113 CIN2/3 were HPV16 (26.5%), HPV35 (19.5%), and HPV58 (12.4%). CD4 count was negatively associated with prevalence of hrHPV (P<0.001) and CIN2/3 among non-users of cART (P=0.013). Combination antiretroviral therapies users (⩾2 year) had lower hrHPV prevalence (prevalence ratio (PR) vs non-users=0.77, 95% confidence interval (CI): 0.61–0.96) and multiple infections (PR=0.68, 95% CI: 0.53–0.88), but not fewer CIN2/3. The positive predictive value of hrHPV-positivity for CIN2/3 increased from 28.9% at age <35 years to 53.3% in ⩾45 years.

Conclusion:

The burden of hrHPV and CIN2/3 was high and it was related to immunosuppression level. Combination antiretroviral therapies ( ⩾2 year) use had a favourable effect on hrHPV prevalence but cART in our population may have been started too late to prevent CIN2/3.     

HPV testing as a triage for borderline or mild dyskaryosis on cervical cytology: results from the Sentinel Sites study

Background:

Earlier pilot studies of human papillomavirus (HPV) triage concluded that HPV triage was feasible and cost-effective. The aim of the present study was to study the impact of wider rollout of HPV triage for women with low-grade cytology on colposcopy referral and outcomes.

Methods:

Human papillomavirus testing of liquid-based cytology (LBC) samples showing low-grade abnormalities was used to select women for colposcopy referral at six sites in England. Samples from 10 051 women aged 25–64 years with routine call or recall cytology reported as borderline or mild dyskaryosis were included.

Results:

Human papillomavirus-positive rates were 53.7% in women with borderline cytology and 83.9% in those with mild dyskaryosis. The range between sites was 34.8–73.3% for borderline cytology, and 73.4–91.6% for mild dyskaryosis. In the single site using both LBC technologies there was no difference in rates between the two technologies. The positive predictive value of an HPV test was 16.3% for CIN2 or worse and 6.1% for CIN3 or worse, although there was considerable variation between sites.

Conclusion:

Triaging women with borderline cytological abnormalities and mild dyskaryosis with HPV testing would allow approximately a third of these women to be returned immediately to routine recall, and for a substantial proportion to be referred for colposcopy without repeat cytology. Variation in HPV-positive rates results in differing colposcopy workload.     

Reflex Human Papillomavirus Test Results as an Option for the Management of Korean Women With Atypical Squamous Cells Cannot Exclude High‐Grade Squamous Intraepithelial Lesion

Background.

Current guidelines recommend initial colposcopy with biopsy regardless of human papillomavirus (HPV) test results in women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). The purpose of this study was to evaluate the value of HPV testing in women with ASC-H based on colposcopic pathology results.

Materials and Methods.

A multicenter cross-sectional study was carried out at three academic hospitals and involved 40,847 Korean women who underwent cervical cancer screening with cytology and HPV tests with or without subsequent colposcopic biopsies between January 2007 and December 2013.

Results.

ASC-H was diagnosed in 276 women (0.7%). Only 6 of 68 (8.8%) women with ASC-H who were HPV negative had cervical intraepithelial neoplasia grade ≥2 (CIN ≥2) lesions, whereas 47.4% of the women with ASC-H who were HPV positive had CIN ≥2 lesions. No cases of invasive cervical cancer were diagnosed among women with ASC-H who were HPV negative. Logistic regression analysis was performed using the group with normal Papanicolaou test results and HPV-negative status as the reference group. Women with ASC-H who were HPV positive had a significantly increased risk of CIN ≥2 lesions, whereas no significant increase was observed in patients with ASC-H and HPV-negative status.

Conclusion.

If the result of the HPV test was negative, the risk of CIN ≥2 lesions in Korean women with ASC-H cytology was low. Reflex HPV testing should be an option for the management of women with cytology showing ASC-H to decrease unnecessary colposcopic biopsies, which are expensive and invasive.

Implications for Practice:

Current American Society for Colposcopy and Cervical Pathology guidelines recommend universal colposcopy for the management of women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on cytology, regardless of human papillomavirus (HPV) test results. The present study suggested that HPV cotesting in patients with ASC-H cytology can provide more detailed and useful information regarding the risk of high-grade cervical intraepithelial neoplasia (CIN) lesions and the need for further treatment. When the result of the HPV test was negative, the risk of CIN lesions of grade ≥2 in women with ASC-H cytology was low. Consequently, reflex HPV testing, rather than immediately performance of invasive and expensive colposcopy with biopsy, should be an option for the management of women with ASC-H.