Safety and efficacy of topical artesunate for the treatment of vulvar intraepithelial neoplasia 2/3.

OBJECTIVE: To evaluate the safety, tolerability, and efficacy of topical artesunate ointment for treatment of biopsy-confirmed Human papillomavirus (HPV)-associated Vulvar intraepithelial neoplasia (VIN) 2/3. METHODS: Participants were enrolled on a prospective, IRB-approved, dose-escalation phase I trial testing either 1, 2 or 3 treatment cycles (5 days), every other week, as applicable. Clinical assessments were completed prior to each dose cycle and included exam and review of adverse event (AE) diary cards. HPV testing and colposcopy was completed at 15 and 28 weeks. AEs were assessed according to CTCAE 4.0 criteria. Complete responders (CR) underwent biopsy of the treated site at the 28-weeks while partial (PR) and non (NR)-responders underwent surgical resection or biopsy and ablation. RESULTS: Fifteen patients consented to and began treatment. Per-protocol assessments were completed in 100% at 15- and 80% at 28-weeks. All patients completed prescribed cycles with no grade 3 or 4 AEs. Vulvovaginal burning/ was the most common AE occurring in 93.3%. AEs were grade 2 in 23.7% and included vulvovaginal pruritus (n = 3), swelling (n = 3) and candidiasis (n = 2). The highest ORR was in the 3-cycle group (88.9% with 55.6% CR). HPV-16 was detected either alone (46.7%) or with other subtypes (33.3%) in 80% of lesions and 5 of 8 (62.5%) with CR had complete viral clearance. CONCLUSIONS: Topical artesunate for treatment of high-grade VIN shows high tolerability, low toxicity and evidence for clinical response in this initial small series. The safety and observed responses support further study in a Phase II trial.

Empowering Low-Income Asian American Women to Conduct Human Papillomavirus Self-Sampling Test: A Community-Engaged and Culturally Tailored Intervention.

BACKGROUND: Asian American women face disproportionate burden of cervical cancer (CC) than non-Hispanic white women in the U.S. The goal of this study was to assess the feasibility and impact of a culturally tailored intervention to promote Human papillomavirus (HPV) self-sampling test among hard-to-reach Asian American women. METHODS: We adopted the community-based participatory research (CBPR) approach to conduct this efficacy study. A total of 156 female participants (56 Chinese, 50 Korean, and 50 Vietnamese) were recruited from community-based organizations (CBOs) in the greater Philadelphia metropolitan area. The intervention components included HPV-related education, HPV self-sampling test kit and instructions, group discussions, and patient navigations, all available in Asian languages. We examined several outcomes, including the completion of HPV self-sampling, HPV-related knowledge, perceived social support, self-efficacy, and comfort with the self-sampling test at post-intervention assessment. RESULTS: The majority of Asian American women had low annual household income (62.3% earned less than $20,000) and low educational attainment (61.3% without a college degree). We found significant increase in participants' knowledge on HPV (baseline: 2.83, post: 4.89, P <.001), social support (baseline: 3.91, post: 4.09, P < .001), self-efficacy (baseline: 3.05, post: 3.59, P < .001), and comfortable with HPV self-sample test (baseline: 3.62, post: 4.06, P < .001). CONCLUSION: To the best of our knowledge, this is the first intervention study that promoted HPV self-sampling test among Asian American women. Our findings showed that CBPR culturally tailored intervention of self-sampling was highly effective in empowering low-income Asian American women to conduct HPV self-sampling tests.

Evaluation of p16INK4a immunocytology and human papillomavirus (HPV) genotyping triage after primary HPV cervical cancer screening on self-samples in China.

OBJECTIVE: Self-sampling for human papillomavirus (HPV) testing is an effective option to increase the cervical screening coverage. How to best triage HPV-positive self-samples remains controversial. Here, we evaluated the performance of a novel p16INK4a immunocytology approach (p16) and HPV genotyping in triaging HPV-positive self-samples. METHODS: A cohort of 73699 women were screened via SeqHPV assay on self-samples. HPV-positive women who met any sequential positive result of HPV16/18 or VIA or p16 were referred for colposcopy. A triage strategy was considered favorable if the NPV for CIN3+ was ≥98%, combined with an improvement of sensitivity and specificity in comparison to the comparator, being the 'ASC-US+' triage and the guideline strategy (HPV16/18+ or ASC-US+). RESULTS: A total of 3510 HPV-positive women were included, 422 (12.0%) CIN2+ and 247 (7.0%) CIN3+ were identified. The positivity of p16 and ASC-US+ were 36.3% and 22.2%, respectively. p16 was more sensitive and less specific than ASC-US+ (P < 0.0001). However, when combined p16 with cytology or genotypes, two triage strategies were superior to the 'ASC-US+' strategy: p16 scored 3+; HPV16/33/58/31+ &p16+. Moreover, four strategies were favorable to the guideline strategy: ASC-US+ or p16+; LSIL+ or p16+; HPV16+ or p16+; HSIL+ or p16+ or HPV16+. These strategies achieved better balance between diseases detection and colposcopy referral. CONCLUSIONS: Our findings indicate the promising utility of p16 immunocytology via adjusting the staining score or serving as an ancillary tool to liquid-based cytology or combining with genotyping for the triage of HPV-positive self-samples, which promotes the precise screening of cervical cancer.

Thermocoagulation versus cryotherapy for the treatment of cervical precancers.

AIM: To compare thermocoagulation and cryotherapy for treatment of high-grade cervical intraepithelial neoplasia (CIN). METHODS: From May 2017 to May 2018, women with CIN2/3 were randomized to thermocoagulation or cryotherapy at Peking University Shenzhen Hospital. Follow-up at 4 and 8 months included cytology and human papillomavirus (HPV) testing. Women who were HPV-positive or had atypical squamous cells of undetermined significance or higher-grade disease underwent colposcopy/biopsy. RESULTS: Among 149 women enrolled, 74 were randomized to thermocoagulation, and 75 to cryotherapy (excluded four were immediately referred for thermocoagulation due to large lesions). At follow-up, there was no difference between the thermocoagulation and cryotherapy groups in HPV-negative (4/8 months: 72.5%/86.2% vs 68.6%/80.6%) and pathology-negative (97.1%/98.5% vs 94.3%/92.3%) rates (all P > 0.05). The cytology-negative rate was similar for thermocoagulation and cryotherapy at 4 months (79.7% vs 78.9%, P > 0.05), but higher for thermocoagulation at 8 months (100% vs 88.7%, P < 0.05). No lesions were observed among the four referral women at follow-up. As compared with cryotherapy, thermocoagulation was associated with shorter duration of treatment and less vaginal discharge, but higher pain during application and longer bleeding after treatment. CONCLUSION: Thermocoagulation was as effective and safe as cryotherapy and might be easily applied to treat high-grade cervical lesions.

Evaluation of Cobas HPV and SeqHPV Assays in the Chinese Multicenter Screening Trial.

OBJECTIVE: The aim of the study was to evaluate the Cobas 4800 Assay and the SeqHPV Assay with self (S) and direct (D) cervical samples in the Chinese Multicenter Screening Trial (CHIMUST). MATERIALS AND METHODS: The CHIMUST is a large population-based multicenter clinical trial, and 10,885 women aged 30-59 years from 15 sites in 7 provinces with no cervical cancer screening for 3 years were eligible. All participating women contributed one self-collected sample (S) and 1 physician-collected endocervical sample (DL). The self-collected sample was first applied to the solid media transport card (SS), and then, the brush placed in 6 mL of ThinPrepSolution (SL). All samples were tested with Cobas 4800 and SeqHPV high-risk HPV assays. Patients human papillomavirus positive (self or direct) were recalled for colposcopy and biopsies. RESULTS: A total of 10,399 women had complete data. The mean age was 43.9 years. A total of 1.4% (142/10,399) had cervical intraepithelial neoplasia (CIN) 2+ and 0.5% (54/10,339) had CIN 3+. In the liquid specimens, the overall HPV infection rates were 10.8% for Cobas and 10.9% for SeqHPV in D sample, and 13.7% for Cobas and 11.6% for SeqHPV in SL sample, respectively. The sensitivity of Cobas-DL, Cobas-SL, SeqHPV-DL, and SeqHPV-SL for CIN 2+ was 95.07%, 95.07%, 94.33%, and 96.48%, respectively. The specificity of Cobas-DL, Cobas-SL, SeqHPV-DL, and SeqHPV-SL for CIN 2+ was 90.38%, 87.35%, 90.21%, and 89.53%, respectively. There were no differences in sensitivity when applying the 2 assays to both self- and directly collected samples in liquid transport media (p > .05). CONCLUSIONS: Both Cobas and SeqHPV screening assays using both self-collected and directly endocervical collected specimens demonstrate similar sensitivity for the detection of CIN 2+ and CIN 3+.

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.

Evaluation of Liquid Versus Dry Specimen Transport With a Newly Validated Isothermal Amplification High-Risk Human Papillomavirus Assay.

OBJECTIVE: The aim of the study was to determine whether the proportion of positive high-risk human papillomavirus (HR-HPV) tests in endocervical specimens transported dry differs from paired specimens transported in liquid media. METHODS: Five hundred women aged of 30 to 55 years were recruited, Shanxi Bethune Hospital, China. Two samples were collected from the endocervix per patient, one placed into empty vial, the other into a liquid transport solution. All samples were analyzed by AmpFire HR-HPV assay. RESULTS: Total 1,000 samples collected from 500 patients were analyzed by the AmpFire HR-HPV assay. The total invalid rate was 0.2% (2/1,000). The proportion of endocervical samples testing positive for HR-HPV transported dry (42.2%, 210/498 [95% CI = 37.8%-46.6%]) was similar to the proportion of paired endocervical samples testing positive transported in liquid media (40.4%, 201/498 [95% CI = 36.0%-44.8%], p = .18 [McNemar test]). That the 2 transport methods are likely measuring the same positive (and negative) specimens is suggested by the finding that κ value for the correlation of positive HR-HPV in endocervical specimens transported dry with those transported in liquid media was 0.86 (95% CI = 0.81-0.90). CONCLUSIONS: Endocervical specimens transported dry have similar proportion of positive HR-HPV tests as those transported in liquid media. Dry brush transport of endocervical samples paired with the special characteristics of AmpFire HR-HPV may become an important addition to population based cervical cancer screening.

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.

Prevalence and sociodemographic correlates of cervicovaginal human papillomavirus (HPV) carriage in a cross-sectional, multiethnic, community-based female Asian population.

OBJECTIVES: Cervical cancer is a largely preventable disease, and the strategic implementation of a cervical cancer prevention programme is partly dependent on the impact of human papillomavirus (HPV) infection interpreted within the context of the country's sociodemographic attributes. The objective of this study is to determine the prevalence of cervicovaginal HPV infection among a healthy, community-based, multiethnic Malaysian population. The HPV prevalence was subsequently correlated to the individual's sociodemographics and sexual/reproductive history. Of significance, the observed prevalence captured was in a birth cohort not included in the national school-based HPV vaccination programme. METHODS: This was a cross-sectional study where 1293 healthy women aged between 18 and 60 years were recruited via convenience sampling from five community-based clinics in Selangor, Malaysia. Cervicovaginal self-samples were obtained and DNA was extracted for HPV detection and genotyping. A comprehensive questionnaire was administered to determine the sociodemographics and behavioural patterns of participants. RESULTS: The median age at enrolment was 37 years old (IQR: 30-47). In total, 86/1190 (7.2%) of the samples collected were positive for HPV infection, with the highest HPV prevalence (11.9%) detected in the subgroup of 18-24 years old. The top three most prevalent HPV genotypes were HPV 16, 52 and 58. The independent risk factors associated with higher rates of HPV infection included Indian ethnicity, widowed status and women with partners who are away from home for long periods and/or has another sexual partner. CONCLUSIONS: The overall prevalence of HPV infection in this Malaysian multiethnic population was 7.2%, with 6.5% being high-risk genotypes. The top three most common high-risk HPV types were HPV 16, 52 and 58. This information is important for the planning of primary (HPV vaccination) and secondary (screening) cervical cancer prevention programmes in Malaysia.

Mailed Human Papillomavirus Self-Collection With Papanicolaou Test Referral for Infrequently Screened Women in the United States.

BACKGROUND: Testing for high-risk human papillomavirus (HPV) infection using mailed, self-collected samples is a promising approach to increase screening in women who do not attend clinic screening at recommended intervals. METHODS: To assess this intervention among high-risk women in the United States, 429 women without a Papanicolaou (Pap) test in 4 or more years (overdue by US guidelines) were recruited from the general population. Participants aged 30 to 65 years were mailed a kit to self-collect a cervicovaginal sample at home, return the sample by mail, and receive HPV results by telephone, with referral to follow-up cytological Pap testing at a local clinic. Cervicovaginal self-samples were collected with a Viba brush, stored in Scope mouthwash, and tested by Hybrid Capture 2. Data were collected in 2010 to 2011 and analyzed in 2017. RESULTS: Two-thirds (64%) of participants returned a self-collected sample, of whom 15% tested HPV DNA positive. Human papillomavirus self-test-positive women reported higher rates of follow-up Pap tests (82%) than did those with self-test negative results (51%). No demographic differences were found in self-test return rate or HPV positivity. High acceptability was reported in participant surveys: most women (81%) had "mostly positive" overall thoughts about the self-test, and most reported being comfortable receiving the kit in the mail (99%), returning their self-collected sample by mail (82%), and receiving their test results by telephone (97%). CONCLUSIONS: Conducting HPV self-testing through population-based recruitment, mailed kit delivery and return by mail, and results delivery by telephone has the potential to reach a broad segment of US underscreened women.

Genotyping for Human Papillomavirus Types 16 and 18 in Women With Minor Cervical Lesions: A Systematic Review and Meta-analysis.

BACKGROUND: High-risk human papillomavirus (hrHPV) testing to triage women with minor cervical lesions generates many referrals. PURPOSE: To evaluate the accuracy of genotyping for HPV types 16 and 18 and its utility as a second triage step after hrHPV testing in women with minor cervical lesions. DATA SOURCES: Searches of 4 bibliographic databases, without language restrictions, from 1 January 1999 to 1 February 2016. STUDY SELECTION: Studies involving women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL) who were triaged with tests for hrHPV and HPV 16/18 to find cervical intraepithelial neoplasia (grade ≥2 [CIN2+] or grade ≥3 [CIN3+]). DATA EXTRACTION: Independent study selection, extraction of data, and quality assessment by 2 reviewers. DATA SYNTHESIS: Twenty-four moderate- to good-quality studies involving 8587 women with ASC-US and 5284 with LSIL were found. The pooled sensitivity of HPV 16/18 genotyping for CIN3+ was about 70% for women with either ASC-US or LSIL. The pooled specificity (with a threshold of grade <2 CIN) was 83% (95% CI, 80% to 86%) for women with ASC-US and 76% (CI, 74% to 79%) for those with LSIL. The average risk for CIN3+ was 17% and 19% in HPV 16/18-positive women with ASC-US and LSIL, respectively, and was 5% in hrHPV-positive but HPV 16/18-negative women with either ASC-US or LSIL. LIMITATION: Methodological and technical heterogeneity among studies; insufficient data to assess accuracy of separate assays. CONCLUSION: Testing for HPV 16/18 to triage women with minor abnormal cytology is poorly sensitive but may be useful as a second triage test after hrHPV testing, with direct referral if the woman is positive for HPV 16/18. Whether colposcopy or repeated testing is recommended for hrHPV-positive but HPV 16/18-negative women depends on local decision thresholds that can be derived from pretest-posttest probability plots. PRIMARY FUNDING SOURCE: 7th Framework Programme of the European Commission.

HPV L1 and P16 Expression in CIN1 to Predict Future CIN2.

The goal of this study was to use the biomarkers human papillomavirus (HPV) L1 and p16 to develop an algorithm that could triage the individual patient with CIN1 at risk for progression. A total of 82 patients initially diagnosed with CIN1 at Peking University Shenzhen Hospital in China had their initial and follow-up paraffin-embedded tissue blocks immune-stained for HPV L1 capsid protein and p16. For CIN1, any staining of abnormal epithelium was considered positive. All patients were followed until they developed CIN2+ or for ≥3 years. About 38 patients regressed (HPV-, Cytology-), 17 persisted (CIN1), and 27 progressed (≥CIN2+). At initial diagnosis, HPV L1 capsid protein was expressed in 42.7% of the CIN1 cases. There was no difference in L1 expression among the 3 groups. However, p16-positive staining in the progression group was significantly higher than in the regression group (P<0.05). In the regression group, the proportion of HPV L1-/p16- category was significantly higher than that in the progression group. In the progression group, when CIN1 lesions progressed to CIN2+, the L1-positive rate was significantly decreased from 51.9% to 18.5%, the p16+/HPV L1+ rate decreased from the initial (44.4%) to the final diagnosis (14.8%), and the p16+/HPV L1- rate increased from the initial (25.9%) to the final diagnosis (66.7%). P16 expression is a clear risk factor for the progression of CIN1. The p16-/HPV L1- pattern was significantly associated with the regression of CIN1. Moving from CIN1 to CIN2+ over time, p16+/HPV L1+ decreased, and p16+/HPV L1- increased. Unfortunately, our objective of finding a sensitive and specific triage algorithm for the individual patient with CIN1 was not achieved.

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.

Cost-Effectiveness of Primary HPV Testing, Cytology and Co-testing as Cervical Cancer Screening for Women Above Age 30 Years.

BACKGROUND: Cervical cancer screening guidelines for women aged ≥30 years allow for co-testing or primary cytology testing. Our objective was to determine the test characteristics and costs associated with Cytology, HPV and Co-testing screening strategies. MAIN METHODS: Retrospective cohort study of women undergoing cervical cancer screening with both cytology and HPV (Hybrid Capture 2) testing from 2004 to 2010 in an integrated health system. The electronic health record was used to identify women aged ≥30 years who had co-testing. Unsatisfactory or unavailable test results and incorrectly ordered tests were excluded. The main outcome was biopsy-proven cervical intraepithelial neoplasia grade 3 or higher (CIN3+). KEY RESULTS: The final cohort consisted of 99,549 women. Subjects were mostly white (78.4 %), married (70.7 %), never smokers (61.3 %) and with private insurance (86.1 %). Overall, 5121 (5.1 %) tested positive for HPV and 6115 (6.1 %) had cytology ≥ ASCUS; 1681 had both and underwent colposcopy and 310 (0.3 %) had CIN3+. Sensitivity for CIN3+ was 91.9 % for Primary Cytology, 99.4 % for Co-testing, and 94.8 % for Primary HPV; specificity was 97.3 % for Co-testing and Primary Cytology and 97.9 % for Primary HPV. Over a 3-year screening interval, Primary HPV detected more cases of CIN3+ and was less expensive than Primary Cytology. Co-testing detected 14 more cases of CIN3+ than Primary HPV, but required an additional 100,277 cytology tests and 566 colposcopies at an added cost of $2.38 million, or $170,096 per additional case detected. CONCLUSIONS: Primary HPV was more effective and less expensive than Primary Cytology. Primary HPV screening appears to represent a cost-effective alternative to Co-testing.

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.

Intimate Partner Violence and Barriers to Cervical Cancer Screening: A Gynecologic Oncology Fellow Research Network Study.

OBJECTIVES: The aims of the study were to examine barriers to cervical cancer screening among women who have experienced intimate partner violence (IPV) and accessed domestic violence shelters, to compare barriers among those up-to-date (UTD) and not UTD on screening, and to evaluate acceptability of human papillomavirus self-sampling. MATERIALS AND METHODS: This is a cross-sectional survey in which domestic violence shelters in Ohio were identified and women completed an anonymous survey assessing UTD screening status, barriers related to screening, history of IPV, intention to follow up on abnormal screening, and acceptability of self-sampling. Characteristics of UTD and not UTD women were compared using Mann-Whitney U tests. RESULTS: A total of 142 women from 11 shelters completed the survey. Twenty-three percent of women were not UTD. Women who were not UTD reported more access-related barriers (mean = 2.2 vs 1.8; p = .006). There was no difference in reported IPV-related barriers between women who were not UTD and those who are UTD (mean = 2.51 in not UTD vs 2.24 in UTD; p = .13). Regarding future screening, of the women who expressed a preference, more women not UTD preferred self-sampling than UTD women (32% vs 14%; p = .05). CONCLUSIONS: In this study, access-related barriers were more commonly reported among women not UTD with screening. Addressing these barriers at domestic violence shelters may improve screening among not UTD women. Self-sampling may also be one feasible approach to support screening in this population.

Recommendations for screening and early detection of common cancers in India.

Cancers of the breast, uterine cervix, and lip or oral cavity are three of the most common malignancies in India. Together, they account for about 34% of more than 1 million individuals diagnosed with cancer in India each year. At each of these cancer sites, tumours are detectable at early stages when they are most likely to be cured with standard treatment protocols. Recognising the key role that effective early detection and screening programmes could have in reducing the cancer burden, the Indian Institute for Cytology and Preventive Oncology, in collaboration with the US National Cancer Institute Center for Global Health, held a workshop to summarise feasible options and relevant evidence for screening and early detection of common cancers in India. The evidence-based recommendations provided in this Review are intended to act as a guide for policy makers, clinicians, and public health practitioners who are developing and implementing strategies in cancer control for the three most common cancers in India.

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.