Loop Electrosurgical Excision Procedure or Cervical Conization to Exclude Cervical Cancer Before Simple Hysterectomy.

OBJECTIVE: The aim of the study was to determine which women require loop electrosurgical excision procedure (LEEP) or cervical conization (cone) to exclude cervical cancer after colposcopy for evaluation of abnormal cervical cancer screening tests yet before simple hysterectomy. MATERIALS AND METHODS: Review of electronic medical records from colposcopy clinics followed by chart review of women with cervical cancer was conducted. RESULTS: Of 18,537 cervical colposcopies for evaluation of abnormal cervical cancer screening tests, 0.6% (103/18,537) had cervical cancer; of 103 women with cervical cancer, 57 had neither cervical biopsy nor endocervical curettage (ECC) showing cancer or rule-out cancer (occult cancers) and were diagnosed by subsequent LEEP (n = 22), cone (n = 31), failed cone (n = 1), or hysterectomy (n = 3). The relative risk of occult cervical cancer at colposcopy for ECC of cervical intraepithelial neoplasia (CIN) 2 or CIN 3 versus ECC not CIN 2 or CIN 3 was 51.5 (5.0% vs 0.1%), for cervical biopsy of CIN 3 versus not CIN 3, was 34.5 (3.9% vs 0.1%), and for colposcopic impression of CIN 2, CIN 3, or cancer (CIN 2+) versus impression not CIN 2+, was 8.5 (1.9% vs 0.2%). If the 10.9% (2,018/18,537) of colposcopies with ECC of CIN 2 or CIN 3, cervical biopsy of CIN 3, or colposcopic impression of CIN 2+ had subsequent LEEP or cone, 96.5% (55/57) of occult cervical cancers would be detected before hysterectomy. CONCLUSIONS: After colposcopy, women with ECC of CIN 2 or CIN 3, cervical biopsy of CIN 3, or colposcopic impression of CIN 2+ require LEEP or cone before simple hysterectomy.

Key Determinants of the Value of Random Cervical Biopsy at Colposcopy.

OBJECTIVE: The aim of the study was to assess whether lower proportions of cervical intraepithelial neoplasia 2+ diagnosed by random biopsy are from lower cut points defining an abnormal colposcopic impression or obtaining only one random biopsy when colposcopic impression is normal. METHODS: We compared colposcopy experiences within Shanxi Province Cervical Cancer Screening Study (SPOCCS) (n = 1,383) and Shenzhen Cervical Cancer Screening Trial (SHENCCAST) (n = 631), which had instructive differences in the cut point defining an abnormal colposcopic impression. RESULTS: The proportion of CIN 2+ diagnosed by random biopsy in SPOCCS (35.0%, 141/403) was higher than SHENCCAST (18.4%, 35/190, p < .001). Quadrant-specific receiver operating characteristic curves for diagnosis of CIN 2+ by colposcopic impression in SPOCCS and SHENCCAST were similar; a lower cut point for an abnormal colposcopic impression in SHENCCAST resulted in lower proportion of CIN 2+ diagnosed by random biopsy. Normal colposcopic impression was found in 85.1% (120/141) of cases of CIN 2+ diagnosed by random biopsy in SPOCCS and in 57.1% (20/35) of such cases in SHENCCAST. Of CIN 2+ diagnosed by random cervical biopsy with normal colposcopic impression, one cervical quadrant was involved with CIN 2+ in 66.7% (80/120) of colposcopies in SPOCCS and 80% (16/20) of colposcopies in SHENCCAST. CONCLUSIONS: Colposcopy series with higher proportions of CIN 2+ diagnosed by random biopsy likely have more stringent cut points defining an abnormal colposcopic impression and have more random biopsies when the colposcopic impression is normal. At colposcopy, we advise multiple biopsies of all acetowhite epithelium or multiple random biopsies to increase the sensitivity of colposcopy.

Evaluation of Viral Load as a Triage Strategy With Primary High-Risk Human Papillomavirus Cervical Cancer Screening.

OBJECTIVE: The aim of the study was to evaluate the human papillomavirus (HPV) viral load combined with cytology as a secondary screening strategy after primary HPV screening. MATERIALS AND METHODS: The data referring to direct Hybrid Capture 2 (HC2), cytology, and histology from Shenzhen Cervical Cancer Screening Trial II were re-analyzed to determine the correlation between viral load and cervical lesions. In addition, algorithms using different viral loads as cut points for immediate colposcopy plus cytology triage were compared with several recommended or controversial primary screening methods. RESULTS: A total of 8,556 women with a mean age of 38.9 years were included in the analysis, of which 13.67% tested high-risk HPV positive with a prevalence of 2.72% for cervical intraepithelial neoplasia 2+ (CIN 2+) and 1.65% for CIN 3+. A significant correlation was observed between increasing relative light units/control (RLU/CO) values and worsening cervical lesions. The mean RLU/CO values for negative, CIN 1, CIN 2, CIN 3, and cancer were 6.86, 119.43, 410.90, 449.39, and 853.26, respectively. A larger proportion of HPV infections with relative high viral load (≥10 RLU/CO) were found in higher-grade lesions. The algorithm using 10 or greater RLU/CO as cut point for immediate colposcopy followed by triage cytology for the other positive (≥1 < 10 RLU/CO) had sensitivity of 93.13%/96.45% and specificity of 92.32%/91.44% for CIN 2+/3+, and the colposcopy referral rate was 10.00%. CONCLUSIONS: Human papillomavirus viral load level is positively associated with cervical lesion grade. Ten relative light units/control or greater is a viable threshold for immediate colposcopy whereas 1 or greater or less than 10 RLU/CO is advised to reflex cytology for optimizing sensitivity and specificity, as well as referral rates.

p16 Immunohistochemistry in Colposcope-Directed and Random Cervical Biopsies of CIN2 and CIN3.

OBJECTIVE: The aim of this study was to determine if there is a different p16 expression pattern between colposcope-directed and random (colposcope-undetectable) biopsies of cervical intraepithelial neoplasia (CIN2) and CIN3. METHODS: Cervical biopsies that were positive for CIN2 or CIN3 were selected from a database of samples acquired during a large population-based clinical trial in Guangdong Province in China (Shenzhen Cervical Cancer Screening Study II). Blocks were recut, reread, and then immunostained for p16. Biopsies were categorized as either colposcope-directed or random biopsies. Diffuse staining was considered p16 positive, whereas focal or no staining was considered p16 negative. Differences were determined by the Fisher exact test. RESULTS: Among the patients with CIN3, there were 232 individual biopsies of CIN3. Sixty were randomly collected, and 172 were colposcopy directed. p16 positivity for the colposcope-directed and random biopsies was 97.7% and 91.7%, respectively (p = 0.052). Like the CIN3 biopsies, colposcope-directed and random CIN2 samples expressed p16 similarly (86.8% [46/53] and 82.6% [19/23], p = .73, respectively). CONCLUSIONS: Based on our data, even small colposcope-undetectable biopsies of CIN3 are significant. Random biopsies of CIN2 or CIN3 demonstrate similar p16 positivity as visible lesions and therefore might be expected to have a similar natural history.

High-Grade Cervical Intraepithelial Neoplasia Detected by Colposcopy-Directed or Random Biopsy Relative to Age, Cytology, Human Papillomavirus 16, and Lesion Size.

OBJECTIVE: The aim of the study was to determine whether p16 positive/cervical intraepithelial neoplasia (CIN) 2, 3, and cancer (p16 + CIN 2/3+) detected by colposcopy-directed or random biopsy differ by age, referral cytology, human papillomavirus (HPV) 16, and lesion size. MATERIALS AND METHODS: Data from the Shenzhen Cervical Cancer Screening Trial II where, at colposcopy, women who had directed and random cervical biopsies were reviewed to find women with CIN 2, 3, or cancer; 227 such women identified had their paraffin-embedded tissue blocks recut, reviewed, and then immune stained for p16. Data were analyzed by χ, Fisher exact test, and linear regression. RESULTS: After histopathologic review and p16 staining of CIN 2, 175 women were diagnosed with p16 + CIN 2/3+. When compared with those diagnosed by colposcopy-directed biopsy (n = 138), those diagnosed by random biopsy (n = 37) were more likely to have Cytology-Lo (cytology of negative, atypical squamous cells of undetermined significance, or low-grade squamous intraepithelial lesion; p = .07), less likely to have HPV 16 (p = .041), more likely to be 51 years or older (p = .022), and more likely to have 1 quadrant lesions (p < .001). Logistic regression analysis showed p16 + CIN 2/3+ diagnosed by random biopsy was predicted by 1 quadrant lesions (p < .0001) and age of 51 years or older (p = .03) but not by Cytology-Lo (p = .71) nor HPV 16 (p = .26). CONCLUSIONS: Women with p16 + CIN 2/3+ diagnosed by random biopsy are older and less likely to have HPV 16; hence, CIN diagnosed by random biopsy may not be as virulent as CIN diagnosed by colposcopy-directed biopsy. Regardless, we advise that CIN diagnosed by random biopsy be viewed like CIN diagnosed by colposcopy-directed biopsy.

High-Grade Squamous Intraepithelial Lesion Cytology With Negative High-Risk Human Papillomavirus Tests Rarely Diagnoses Endometrial Cancer.

OBJECTIVES: We hypothesized that women with cervical cytologic results of high-grade squamous intraepithelial lesion (HSIL) and negative high-risk human papillomavirus (HR-HPV) test results would have a high risk of having endometrial cancer and would benefit from routine endometrial biopsy. MATERIALS AND METHODS: Reports of women with cytologic results of HSIL and negative HR-HPV test results were found in an electronic colposcopy database; their charts were reviewed. Rates of endometrial cancer for cytologic results of HSIL and negative HR-HPV test results were compared to a historical series for cytologic results of HSIL with positive HR-HPV and cytologic results of atypical glandular cells (AGCs) and negative HR-HPV test results. RESULTS: Between August 10, 1998, and April 20, 2013, 56 women were evaluated in our colposcopy clinics for cytologic results of HSIL and negative HR-HPV test results; of these 56 women, 1 (1.8%) was diagnosed with endometrial cancer. No endometrial cancer was diagnosed during the follow-up (median = 63 mo) after colposcopy. The risk for endometrial cancer with cytologic results of HSIL and negative HR-HPV test results (1.8%, 1/56) did not differ from that of a historical series from 2007 to 2009 from the same colposcopy clinic in 223 women with cytologic results of HSIL and positive HR-HPV test results (0.0%, 0/223; p = .2) and was lower than the risk for endometrial cancer from the historical series from 2007 to 2009 in women with cytologic results of AGC and negative HR-HPV test results (14.4%, 4/27; p = .04). CONCLUSIONS: Women with cytologic results of HSIL and negative HR-HPV test results are more like those with cytologic results of HSIL and positive HR-HPV test results than those with cytologic results of AGC and negative HR-HPV test results and would unlikely to benefit from routine endometrial biopsy at the time of colposcopy.

Factors That Virtually Exclude Cervical Cancer at Colposcopy.

OBJECTIVES: The objective of this work was to determine the risk of invasive cervical cancer at colposcopy based on the woman's age, associated cervical cytology, and colposcopic impression. METHODS: Review of electronic medical records from colposcopy clinics followed by chart review of women with cervical cancer. RESULTS: Between March 1, 1996, and April 23, 2013, 27,381 cervical colposcopies for evaluation of abnormal cervical cytology and/or positive high-risk human papillomavirus tests were performed. Median age at colposcopy was 32 years (range, 11-91 years). Biopsy at colposcopy or at subsequent loop electrocautery excision procedure, cervical conization, or hysterectomy diagnosed cervical cancer in 0.5% (132/27,381) of women. At colposcopy, the risk of cervical cancer for women younger than 30 years was 0.07% (8/12,131), for women with Cytology-Lo (low-grade squamous intraepithelial lesion, atypical squamous cells of uncertain significance, benign endometrial cells, or negative), it was 0.17% (43/25,779); and for women with normal colposcopic impressions, it was 0.17% (18/11,389). The risk of cervical cancer for women younger than 30 years with Cytology-Lo was 0.01% (1/11,663). CONCLUSIONS: At colposcopy, cervical cancer is not excluded by a normal colposcopic examination result, Cytology-Lo, or age younger than 30 years, but is virtually excluded by the combination of age younger than 30 years and Cytology-Lo.

Which Colposcopies Should Include Endocervical Curettage?

OBJECTIVES: Although endocervical curettage (ECC) is often performed at colposcopy, it remains unclear whether it should be done in all women, only women over a certain age, only women with unsatisfactory colposcopy, or only in women with normal colposcopic impressions. To clarify the indications for ECC, we determined the proportion of colposcopies with CIN 3, or cancer (CIN 3+) detected only by ECC showing CIN 2, CIN 3, or cancer (CIN 2+). METHODS: Review of electronic medical records from colposcopy clinics. RESULTS: Between March 1, 1996, and April 23, 2013, approximately 18,537 cervical colposcopies with no missing results evaluated women with abnormal cervical cytology and/or positive high-risk human papillomavirus tests. In 7.5% (1,398/18,537) of colposcopies, the final diagnosis, based on the worst biopsy from cervix; ECC; or subsequent loop electrocautery excision procedure, cervical conization, or hysterectomy, was CIN 3+. The proportion of colposcopies with CIN 3+ detected only by ECC showing CIN 2+ was 0.5% (101/18,537). Limiting the ECC to women with unsatisfactory colposcopy, colposcopic impressions suggestive of CIN 2+, or impressions of normal resulted in fewer ECC performed but also greatly decreased the proportion of CIN 3+ that could have been detected only by ECC showing CIN 2+. Limiting the ECC to colposcopies in women age 25 years and older resulted in 29.3% (5,433/18,537) fewer ECCs while detecting 96.0% (97/101) of the CIN 3+ that could have been detected only by ECC showing CIN 2 + . CONCLUSIONS: Endocervical curettage should be performed at colposcopy in women age 25 and older.

Triage of women with negative cytology and positive high-risk HPV: an analysis of data from the SHENCCAST II/III studies.

OBJECTIVES: To determine a management strategy for women testing negative with cervical cytology and positive for high-risk human papillomavirus (HR-HPV). METHODS: Using the data from the large population-based Shenzhen Cervical Cancer Screening Trials II and III (SHENCCAST II/III), we compared the risk for cervical intraepithelial neoplasia grade 3 or cancer (CIN 3+) in women with negative cytology but testing positive for HR-HPV DNA using Cervista HPV HR or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), followed by secondary screening with type-specific Cervista HPV-16/18 or MALDI-TOF. The study aim was to seek the most sensitive and specific triage assay for referral for colposcopy. RESULTS: A total of 8,556 women had complete data. The proportion of women with negative cytology and positive HR-HPV by Cervista HR-HPV (5.30%, 453/8,556) was slightly lower than that of women with negative cytology and HR-HPV-positive tests by MALDI-TOF (5.82%, 499/8,556, p = .015). The proportion of women having negative cervical cytology and a positive HR-HPV by Cervista HR who have HPV-16 and/or -18 by Cervista HPV-16/18 (11.8%, 53/448) was less than that of women with a negative cervical cytology and positive HR-HPV by MALDI-TOF who have HPV-16 and/or -18 by MALDI-TOF (19.4%, 97/499, p = .001). The proportion of CIN 3+ within negative cervical cytology and positive HR-HPV that were HPV-16 and/or -18 for the Cervista 16/18 assay (61.5%, 8/13) was similar to that for the MALDI-TOF 16/18 assay (66.7%, 10/15, p = 0.8). CONCLUSIONS: In the cytology-negative HR-HPV-positive population, Cervista 16/18 as the HPV detection method would refer 11.8% of women for colposcopy and diagnose 61.5% of the CIN 3+, while MALDI-TOF16/18 would refer 19.4% and diagnose 66.7% of the CIN 3+. Cervista HPV-16/18 seems to be the superior triage test. However, in resource-limited settings, an assay that includes 16/18 genotyping in the primary result (rather than a second test) may be more cost efficient.

Yield and mode of diagnosis of cervical intraepithelial neoplasia 3 or cancer among women with negative cervical cytology and positive high-risk human papillomavirus test results.

OBJECTIVE: In women with negative cervical cytology and positive high-risk human papillomavirus (HR-HPV) test results, we compared the risk of cervical intraepithelial neoplasia 3 (CIN 3) or cancer (CIN 3+) in women with previous abnormal cervical cytology, CIN, or HR-HPV with that in women without this history, and we determined their cumulative risk of CIN 3+. MATERIALS AND METHODS: We reviewed colposcopies for negative cytology and positive HR-HPV test results from 2007 to 2009 (colposcopy was done for previous abnormal cytology, HR-HPV, or CIN or if negative cytology and positive HR-HPV test results for 20-35 months). Women with negative cytology and positive HR-HPV test results in 2007 were reviewed to determine their cumulative risk of CIN 3+. RESULTS: Of the 513 women with colposcopy for negative cytology and positive HR-HPV test results, 367 had previous abnormal cytology, CIN, or HR-HPV greater than 35 months ago and 146 had negative cytology and positive HR-HPV test results for 20 to 35 months. Risk of CIN 3+ for women with negative cytology and positive HR-HPV test results with previous abnormal cytology, HR-HPV, or CIN who did not have previous colposcopy was 11.9% (8/67); for similar women with previous colposcopy, it was 2.7% (8/300); and for women with positive HR-HPV test result for 20 to 35 months, it was 7.5% (11/146). In 2007 to 2009, risk of CIN 3+ for women with cytology of atypical squamous cells of undetermined significance (ASC-US) with positive HR-HPV test result was 3.9% (60/1,540). Of the 1,726 women with negative cytology and positive HR-HPV test result in 2007, 381 (22.1%) were lost to follow-up. Of the 1,345 women with median follow-up of 44 months, 602 (44.8%) had 1 or 2 subsequent negative cytology and negative HR-HPV test results and 180 had subsequent positive HR-HPV test result without biopsy. Of the 563 women with biopsy, there were 711 evaluations. Invasive cancer was found in 4 and CIN 3 in 54 (cumulative CIN 3+ of 4.3%, 58/1,345). Half (29/58) of the cumulative CIN 3+ was diagnosed after subsequent abnormal cytology and positive HR-HPV test result. CONCLUSIONS: If referral to colposcopy of women with cervical cytology of ASC-US and positive HR-HPV test result (CIN 3+, 3.9%) is justified, referral to colposcopy of women with negative cytology and positive HR-HPV test results is justified if they have previous abnormal cervical cytology, CIN, or HR-HPV greater than 35 months ago but have not had previous colposcopy (CIN 3+=11.9%) or are persistently HR-HPV positive for 20 to 35 months (CIN 3+, 7.5%). The risk of CIN 3+ in women with previous abnormal cytology, CIN, or HR-HPV who have previous colposcopy (2.7%) is lower because these women have incident rather than prevalent CIN 3+.

Improved sensitivity of vaginal self-collection and high-risk human papillomavirus testing.

Self-collected vaginal specimens tested for high-risk human papillomavirus (HR-HPV) have been shown to be less sensitive for the detection of cervical intraepithelial neoplasia or cancer (≥CIN 3) than physician-collected endocervical specimens. To increase the sensitivity of self-collected specimens, we studied a self-sampling device designed to obtain a larger specimen from the upper vagina (POI/NIH self-sampler) and a more sensitive polymerase chain reaction (PCR)-based HR-HPV assay. Women (10,000) were screened with cervical cytology and HR-HPV testing of vaginal self-collected and endocervical physician-collected specimens. Women were randomly assigned to use either a novel self-collection device (POI/NIH self-sampler) or conical-shaped brush (Qiagen). The self-collected and clinician-collected specimens were assayed by Cervista (Hologic) and the research only PCR-based matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). Women with any abnormal screening test underwent colposcopy and biopsy. Women (8,556), mean age of 38.9, had complete data; 1.6% had ≥ CIN 3. For either HR-HPV assay, the sensitivity was similar for the two self-collection devices. Tested with Cervista, the sensitivity for ≥CIN 3 of self-collected specimens was 70.9% and for endocervical specimens was 95.0% (p = 0.0001). Tested with MALDI-TOF, the sensitivity for ≥CIN 3 of self-collected specimens was 94.3% and for endocervical specimens was also 94.3% (p = 1.0). A self-collected sample using a PCR-based assay with the capability of very high throughput has similar sensitivity as a direct endocervical specimen obtained by a physician. Large population-based screening "events" in low-resource settings could be achieved by promoting self-collection and centralized high-throughput, low-cost testing by PCR-based MALDI-TOF.

Population-based human papillomavirus 16, 18, 6 and 11 DNA positivity and seropositivity in Chinese women.

To optimize HPV vaccination implementation at the population-level in China, data are needed on age-specific HPV 16, 18, 6 and 11 prevalence. This cross-sectional, population-based study evaluated the age- and type-specific HPV 16, 18, 6 and 11 prevalence of DNA and serum antibodies among women in China. From July 2006 to April 2007, 17-54 year old women from three rural provinces (Xinjiang, Shanxi and Henan) and two cities (Beijing and Shanghai) provided cervical exfoliated cells for HPV DNA and liquid-based cervical cytology (SurePath). High- and low-risk HPV types were detected with HC-II (Qiagen), with genotyping of HPV-positive samples using Linear Array (Roche). HPV 16, 18, 6 and 11 serum antibodies were detected using a Luminex-based, competitive immunoassay (Merck). A total of 4,206 women with DNA and serum antibody results were included. HPV 16 DNA prevalence peaked in women aged 30-34 (4.2%) and 45-49 yr (3.8%), while HPV 18 DNA prevalence peaked at ages 40-44 yr (1.3%). Most women were dually DNA and serum antibody negative: HPV 16 (92.2%), 18 (97.2%), HPV 16 and 18 (90.2%), 6 (92.0%), 11 (96.6%), 6 and 11(89.9%) and HPV 16, 18, 6 and 11 (82.5%). Future national HPV vaccination programs in China should target younger women due to increased exposure to HPV types 16, 18, 6 and 11 with increasing age. Cumulative exposure of HPV may be underreported in this population, as cross-sectional data do not accurately reflect exposure to HPV infections over time.

Seroprevalence of human papillomavirus types 6, 11, 16 and 18 in Chinese women.

BACKGROUND: Human papillomavirus (HPV) seroprevalence data have not previously been reported for different geographical regions of China. This study investigated the cross-sectional seroprevalence of antibodies to HPV 6, 11, 16, and 18 virus-like particles in Chinese women. METHODS: Population-based samples of women were enrolled from 2006 to 2007 in 3 rural and 2 urban areas of China. Each consenting woman completed a questionnaire and provided a blood sample. Serum antibodies were detected using a competitive Luminex immunoassay that measures antibodies to type-specific, neutralizing epitopes on the virus-like particles. RESULTS: A total of 4,731 women (median age 35, age range 14-54) were included, of which 4,211 were sexually active women (median age 37) and 520 virgins (median age 18). Low risk HPV 6 was the most common serotype detected (7.3%), followed by HPV 16 (5.6%), HPV 11 (2.9%), and HPV 18 (1.9%). Overall HPV seroprevalence to any type was significantly higher among sexually active women (15.8%) than virgins (2.5%) (P = 0.005). Overall seroprevalence among sexually active women gradually increased with age. Women from rural regions had significantly lower overall seroprevalence (Odds Ratio (OR) = 0.7; 95% CI: 0.6-0.9, versus metropolitan regions, P < 0.001). With increasing number of sexual partners, women were at higher risk of seropositivity of any type (OR = 2.6; 95% CI: 1.7-3.9 for > = 4 partners versus 1 partner, P < 0.001). Wives were at higher risk of seropositivity for HPV 16/18/6/11 when reporting having a husband who had an extramarital sexual relationship (OR = 2.0; 95% CI: 1.6-2.5, versus those whose husbands having no such relationship, P < 0.001). There was a strong association between HPV 16 seropositivity and presence of high-grade cervical lesions (OR = 6.5; 95% CI: 3.7-11.4, versus normal cervix, P < 0.001). CONCLUSIONS: HPV seroprevalence differed significantly by age, geography, and sexual behavior within China, which all should be considered when implementing an optimal prophylactic HPV vaccination program in China.

Utility of random cervical biopsy and endocervical curettage in a low-risk population.

OBJECTIVE: The study aimed to determine the increase in the yield of cervical intraepithelial neoplasia 3 (CIN 3) or cancer (CIN 3+) from random cervical biopsy in quadrants without visible lesions and endocervical curettage (ECC) in a low-prevalence setting. MATERIALS AND METHODS: Random biopsy and ECC (unless pregnant) have been obtained in the colposcopy clinic of the Southern California Permanente Medical Group (SCPMG)-Fontana since 2004. We reviewed the colposcopy experience of SCPMG-Fontana for January 1, 2007, to December 31, 2009, to determine the method of diagnosis of CIN 3+. RESULTS: Between January 1, 2007, and December 31, 2009, 4677 women with median age 32 years had 4932 colposcopies in the SCPMG-Fontana colposcopy clinics. Cervical intraepithelial neoplasia 3+ was diagnosed in 295 women. Cervical biopsy detected 64.4% of CIN 3+; ECC diagnosed 5.1%; loop electrocautery excision procedure (LEEP) or cervical conization for cervical biopsy and/or ECC of CIN 2 diagnosed 27.8%; LEEP for the cytology of high-grade squamous intraepithelial lesion with cervical biopsy result of negative or CIN 1 diagnosed 1.4%; and LEEP, cervical conization, or biopsy in follow-up of CIN 2 diagnosed 1.4%. Sixty-one of the 295 cases of CIN 3+ (20.7%) were diagnosed after evaluation of random cervical biopsy and/or ECC of CIN 2+. CONCLUSIONS: Random biopsy in cervical quadrants without visible lesions and ECC increased the yield of CIN 3+ in this low-risk colposcopy setting. Endocervical curettage can be omitted in women younger than 25 years.

Regardless of skill, performing more biopsies increases the sensitivity of colposcopy.

OBJECTIVES: The objectives of this study were to compare the sensitivity of colposcopically directed biopsy (biopsy of cervical quadrants with colposcopic impressions of human papillomavirus, cervical intraepithelial neoplasia [CIN], or cancer) for CIN 3 or cancer (CIN 3+) among physicians and to estimate the increase in yield of CIN 3+ per colposcopy associated with "random" biopsies and/or endocervical curettage (ECC). METHODS: Two studies in which 7 physicians performed 1,383 colposcopic examinations on women with abnormal cervical cytology were reviewed. At colposcopy, the cervix was divided into quadrants by lines from the 12- to the 6-o'clock and from the 3- to the 9-o'clock positions. Each quadrant was assigned a colposcopic impression of normal, human papillomavirus or CIN 1, CIN 2 or CIN 3, or cancer. Each quadrant had biopsy of colposcopically detected lesions or "random" biopsy at the squamocolumnar junction if the colposcopic impression was normal. Lastly, ECC was obtained. RESULTS: Among the physicians, the sensitivity of colposcopically directed biopsy for CIN 3+ varied from 28.6% to 92.9% (p < .001). With logistic regression, the sensitivity of colposcopically directed biopsy for CIN 3+ increased as the number of cervical quadrants with CIN 3+ increased (p < .001); once corrected for the number of quadrants with CIN 3+, differences between the physician's sensitivities remained significant (p = .01). For 6 of 7 physicians, the yield of CIN 3+ per colposcopy was greater when colposcopically directed biopsy was augmented by up to 4 "random" biopsies plus ECC (p = .03 to p < .001). CONCLUSIONS: The sensitivity of colposcopy for CIN 3+ varies widely. Performing up to 4 "random" biopsies plus ECC increases the yield of CIN 3+.

Prevalence of type-specific human papillomavirus in endocervical, upper and lower vaginal, perineal and vaginal self-collected specimens: Implications for vaginal self-collection.

To determine why a vaginal self-collection tested for high-risk human papillomavirus (HR-HPV) by Hybrid Capture 2(R) (hc2) has lower sensitivity and specificity for cervical intraepithelial neoplasia Grade 2 or worse (> or = CIN 2), we collected 5 specimens (endocervix, upper and lower vagina, perineum, vaginal self-collection) from 2,625 women. Endocervical and self-collected specimens had HR-HPV tests by hc2. All 5 anogenital specimens were tested for 37 HPV genotypes [Linear Array(R), (LA)] from 397 women hc2 positive in endocervical or self-collected specimens and for a randomly selected 71 of 2,228 women hc2 negative on both specimens. Three hundred nintey-five women who screened positive by hc2 or had abnormal cytology underwent colposcopic evaluation. Of 47 women with > or = CIN 2, hc2 was positive in 97.9% (46/47) of endocervical and 80.9% (38/47), p = 0.008 of self-collected specimens. Seven of 9 women with > or = CIN 2 and negative self-collected hc2 tests were positive for HR-HPV by LA. Of 2,578 women without > or = CIN 2, hc2 was positive in 9.8% (253/2,578) of endocervical and 11.4% (294/2,578), p = 0.001 of self-collected specimens. Of the 41 more women without > or = CIN 2 that tested hc2 positive on the self-collected but negative on endocervical specimen, LA tested positive for HR-HPV in 24, negative for HPV in 11 and negative for HR-HPV but positive for low-risk HPV in 6. Lower sensitivity of self-collected specimens is secondary to lower levels of vaginal HR-HPV. The principal cause of the lower specificity of self-collected specimens is HR-HPV present solely in the vagina, which is not associated with > or = CIN 2.

Human papillomavirus testing for cervical cancer screening: results from a 6-year prospective study in rural China.

Long-term follow-up evaluations of cervical screening approaches are limited in low-resource areas. This prospective study assessed the risk of future cervical intraepithelial neoplasia grade 2 or worse (CIN2+) associated with baseline human papillomavirus (HPV) and cytologic status. In rural China, 1,997 women were screened with 6 screening tests, including colposcopic evaluations, and underwent biopsies in 1999. In December 2005, 1,612 women with cervical intraepithelial neoplasia grade 1 or less at baseline were rescreened by visual inspection, liquid-based cytology, and HPV-DNA testing. All women underwent colposcopy at follow-up, with biopsies taken from women with visually apparent lesions or cytologic abnormalities. Twenty women developed incident CIN2+. The crude relative risk of CIN2+ for baseline HPV-positive women was 52 (95% confidence interval: 12.1, 222.5). The crude relative risk of CIN2+ was 167 (95% confidence interval: 21.9, 1,265) for baseline and follow-up repeatedly HPV-positive women compared with repeatedly HPV-negative women. Among 1,374 baseline HPV-negative women, 2 and no incident CIN2+ cases were detected in baseline cytologically normal and abnormal subgroups, respectively. Among 238 baseline HPV-positive women, 6 of 18 incident cases of CIN2+ developed in the cytologically normal group. This study demonstrates that a single oncogenic HPV-DNA test is more effective than cytology in predicting future CIN2+ status.