Selected class I and class II HLA alleles and haplotypes and risk of high-grade cervical intraepithelial neoplasia

Human leukocyte antigens (HLAs) present foreign antigens to the immune system and may be important determinants of cervical neoplasia. Previously published associations between HLA and cervical neoplasia exhibit considerable variation in findings. The biomarkers of cervical cancer risk (BCCR) case-control study addressed the role of specific HLA alleles as cofactors in the development of high-grade cervical intraepithelial neoplasia (HG-CIN) based on the most consistent evidence from published literature. Cases (N = 381) were women with histologically-confirmed HG-CIN attending colposcopy clinics and controls (N = 884) were women from outpatient clinics with normal cytological screening smears. Subjects were mainly of French-Canadian descent. Cervical specimens were tested for human papillomavirus (HPV) DNA and HLA genotypes by PGMY L1 consensus primer PCR and a PCR sequence-specific primer method, respectively. Unlike other studies, the DQB1*03 and DRB1*13 allele groups were not associated with risk of HG-CIN. The B7-DRB1*1501-DQB1*0602 haplotype was associated with a 41% overall reduction in HG-CIN risk (odds ratio [OR] = 0.59; 95% confidence interval [CI]: 0.36-0.96), and an 83% reduction in risk of HG-CIN among HPV 16 or HPV 18-positive subjects (OR = 0.17; 95%CI: 0.05-0.54). Paradoxically, however, the same haplotype was associated with HPV 16/18 infection risk among controls (OR = 8.44, 95%CI: 1.12-63.73). In conclusion, the B7-DRB1*1501-DQB1*0602 haplotype was protective against HG-CIN, especially in individuals infected with oncogenic HPV, but the mechanism of the association seems to involve multiple steps in the natural history of HPV and CIN.     

Clearance of human papillomavirus infection after successful conization in patients with cervical intraepithelial neoplasia

The natural history of high‐risk human papillomavirus (HRHPV) infection after successful treatment of cervical intraepithelial neoplasia (CIN) is not well known. This study was performed to evaluate the rate and pattern of HRHPV infection clearance after successful conization for CIN and to analyze factors associated with such clearance. A total of 287 patients who underwent loop electrosurgical excision procedures (LEEP) owing to HRHPV‐associated CIN were included. All patients had negative resection margins on LEEP specimens and underwent HPV testing with the hybrid capture II system at 3‐, 6‐, 9‐, 12‐, 18‐ and 24‐month follow‐up visits after LEEP. Persistent HPV infections were detected in 45.6%, 14.3%, 6.3%, 2.2%, 1.5% and 1.1% of patients at 3, 6, 9, 12, 18 and 24 months after LEEP, respectively. Clearance rates did not differ by age, parity or severity of cervical lesion. However, clearance rates were significantly slower in patients with HPV DNA loads >500 RLU/PC before LEEP (p = 0.040). During 2 years of follow‐up after LEEP, 24 patients had recurrent disease revealed by biopsy. The odds ratios for recurrent disease in patients with persistent HRHPV infection increased gradually from 5.17 at the 3‐month follow‐up visit to 12.54, 15.69 and 25.90 at 6‐, 9‐, 12‐ and 24‐month follow‐up visits, respectively. We conclude that HRHPV infection cleared gradually in most patients within 6 months of treatment. Clearance rates were significantly slower in patients with HPV DNA loads >500 RLU/PC. Persistent HPV infection was a significant positive predictor of recurrence.     

光动力治疗人乳头瘤病毒感染和宫颈上皮内瘤变的临床应用进展

光动力疗法是联合应用光敏剂及其相关光源,利用光动力学反应选择性破坏肿瘤组织的治疗方法.目前光动力疗法作为一种新的疗法已经在HPV感染和CIN的治疗中广泛应用并取得了良好的治疗效果,通过对国内外光动力疗法在治疗HPV感染及CIN的临床应用的综述,可以为进一步深入研究提供理论依据.     

Chromosomal profiles of high-grade cervical intraepithelial neoplasia relate to duration of preceding high-risk human papillomavirus infection

High-grade cervical intraepithelial neoplasia (CIN2/3) represents a heterogeneous disease both with respect to clinical behavior and chromosomal aberrations detected. We hypothesized that the extent of chromosomal aberrations reflects the duration of their existence. Chromosomal profiles were determined of CIN3 of women with a known 5-year history of high-risk human papillomavirus virus (hrHPV) infection, in which duration of prior hrHPV infection was considered a proxy for duration of CIN3 existence. Eleven women had a <5 year preceding hrHPV infection (CIN3<5yrPHI) and 24 had a PHI lasting ≥5 years (CIN3≥5yrPHI). For comparison, six CIN3 adjacent to squamous cell carcinomas (CIN3-SCC), the corresponding SCCs, and six CIN1 were included. Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two clusters. One was characterized by a low number of chromosomal aberrations and included all CIN1, 81.8% of CIN3<5yrPHI and 33.3% of CIN3≥5yrPHI. Samples in the second cluster, displaying multiple aberrations, included 18.2% of CIN3<5yrPHI, 66.7% CIN3≥5yrPHI, all except one CIN3-SCC and all SCCs. The number of genomic aberrations increased according to lesion grade and also with longer duration of PHI. The increase in aberrations in CIN3≥5yrPHI compared to <5yrPHI was highly significant (p = 0.001), suggesting that CIN3≥5yrPHI represent more severe lesions. In conclusion, longer duration of preceding hrHPV infection is associated with an increased number of chromosomal aberrations. Hence, CIN3 with a longer duration of existence are likely more prone to have an increased short-term risk of cervical cancer.     

Smoking, diet, pregnancy and oral contraceptive use as risk factors for cervical intra-epithelial neoplasia in relation to human papillomavirus infection

Smoking, nutrition, parity and oral contraceptive use have been reported as major environmental risk factors for cervical cancer. After the discovery of the very strong link between human papillomavirus (HPV) infection and cervical cancer, it is unclear whether the association of these environmental factors with cervical cancer reflect secondary associations attributable to confounding by HPV, if they are independent risk factors or whether they may act as cofactors to HPV infection in cervical carcinogenesis. To investigate this issue, we performed a population-based case-control study in the Vasterbotten county of Northern Sweden of 137 women with high-grade cervical intra-epithelial neoplasia (CIN 2-3) and 253 healthy age-matched women. The women answered a 94-item questionnaire on diet, smoking, oral contraceptive use and sexual history and donated specimens for diagnosis of present HPV infection (nested polymerase chain reaction on cervical brush samples) and for past or present HPV infections (HPV seropositivity). The previously described protective effects of dietary micronutrients were not detected. Pregnancy appeared to be a risk factor in the multivariate analysis (P < 0.0001). Prolonged oral contraceptive use and sexual history were associated with CIN 2-3 in univariate analysis, but these associations lost significance after taking HPV into account. Smoking was associated with CIN 2-3 (odds ratio (OR) 2.6, 95% confidence interval (CI) 1.7-4.0), the effect was dose-dependent (P = 0.002) and the smoking-associated risk was not affected by adjusting for HPV, neither when adjusting for HPV DNA (OR 2.5, CI 1.3-4.9) nor when adjusting for HPV seropositivity (OR 3.0, CI 1.9-4.7). In conclusion, after taking HPV into account, smoking appeared to be the most significant environmental risk factor for cervical neoplasia.     

Cumulative risk of cervical intraepithelial neoplasia for women with normal cytology but positive for human papillomavirus: Systematic review and meta-analysis

Most women positive for human papillomavirus (HPV) are cytology normal. The optimal screen-management of these women is unclear given their risk of developing precancer. We performed a systematic review and meta-analysis of progression rates to precancer and cancer for HPV-positive, cytology normal women. We searched MEDLINE, EMBASE and Scopus for prospective studies measuring the cumulative incidence of precancer and cervical cancer in HPV-positive, cytology/histology normal women. Record screening was performed independently by two reviewers. We modeled the cumulative incidence over time using a multilevel random-effects meta-regression model. We used the model to predict HPV type-specific risks of precancer and cancer over follow-up. Data from 162 unique records were used in our analysis. The average incidence rate of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in high-risk HPV positive but cytology/histology normal women was 1.0 per 100 women-years (95% CI: 1.0-1.1). This corresponds to an average cumulative risk at 1, 3 and 5 years of 2.1% (95% prediction interval 0.0-9.5), 4.3% (95% prediction interval 0.0-11.5) and 6.4% (95% prediction interval 0.0-13.5). HPV type was a strong predictor of the risk of oncogenic progression. There was substantial heterogeneity in the background precancer risk across studies (P-value < .0001). Our HPV type-specific progression risk estimates can help inform risk-based cervical cancer screening guidelines for HPV-positive women. However, precancer and cervical cancer risks are highly variable and may not be generalizable between populations.     

Type‐dependent association between risk of cervical intraepithelial neoplasia and viral load of oncogenic human papillomavirus types other than types 16 and 18

Studies of the clinical relevance of human papillomavirus (HPV) DNA load have focused mainly on HPV16 and HPV18. Data on other oncogenic types are rare. Study subjects were women enrolled in the atypical squamous cells of undetermined significance (ASC‐US) and low‐grade squamous intraepithelial lesion (LSIL) triage study who had ≥1 of 11 non‐HPV16/18 oncogenic types detected during a 2‐year follow‐up at 6‐month intervals. Viral load measurements were performed on the first type‐specific HPV‐positive specimens. The association of cervical intraepithelial neoplasia grades 2–3 (CIN2/3) with type‐specific HPV DNA load was assessed with discrete‐time Cox regression. Overall, the increase in the cumulative risk of CIN2/3 per 1 unit increase in log₁₀‐transformed viral load was statistically significant for four types within species 9 including HPV31 (adjusted hazard ratio [HR _adjusted] = 1.32: 95% confidence interval [CI], 1.14–1.52), HPV35 (HR _adjusted = 1.47; 95% CI, 1.23–1.76), HPV52 (HR _adjusted = 1.14; 95% CI, 1.01–1.30) and HPV58 (HR _adjusted = 1.49; 95% CI, 1.23–1.82). The association was marginally significant for HPV33 (species 9) and HPV45 (species 7) and was not appreciable for other types. The per 1 log₁₀‐unit increase in viral load of a group of species 9 non‐HPV16 oncogenic types was statistically significantly associated with risk of CIN2/3 for women with a cytologic diagnosis of within normal limits, ASC‐US, or LSIL at the first HPV‐positive visit but not for those with high‐grade SIL. Findings suggest that the viral load‐associated risk of CIN2/3 is type‐dependent, and mainly restricted to the species of HPV types related to HPV16, which shares this association.     

深圳华侨城不同职业女性生殖道HPV感染与CIN现患率调查

背景与目的:目前全世界公认HPV感染是子宫颈癌的病因。本研究旨在了解深圳市不同职业女性人群的生殖道高危型人乳头瘤病毒(human papillomavirus,HPV)感染现状及子宫颈上皮内瘤样病变(cervical intra-epithelial neoplasia,CIN)的现患率,探讨职业因素在子宫颈癌发病中的作用。方法:2004年11月至12月,在深圳市华侨城对15～59岁1137名有性生活女性居民及辖区工厂和服务业从业妇女进行以人群为基础的流行病学调查。对所有接受筛查的妇女均行电子阴道镜检查、液基细胞薄层涂片技术(liquid-based cytology test,LCT)子宫颈脱落细胞学检查及第二代杂交捕获技术(hybrid captureⅡ,HC-Ⅱ)宫颈脱落细胞中高危型HPV检测。对HPV阳性并且LCT≥未明确诊断意义的不典型鳞状上皮细胞(atypical squamous cells of undetetemined sign,ASCUS)和/或LCT≥低度鳞状上皮内瘤样病变(low grade squamous intraepithelial lesion,LSIL)的妇女行阴道镜下活组织病理学检查,以病理结果作为诊断子宫颈上皮内瘤样病变的金标准。资料采用VFP软件录入和整理,利用χ2检验和非条件Lo-gistic回归分析危险因素和CIN的关系。结果:该人群高危HPV-DNA总检出率为14.0%,社区居民、工厂工人、服务业妇女三种人群的HPV检出率分别为14.1%、9.2%、18.9%,工厂工人HPV感染率明显低于服务业妇女和社区居民(P<0.01和P<0.05)。社区居民和工厂工人各年龄组间HPV感染率差异无显著性(P>0.05),服务业妇女15～24岁和25～29岁HPV感染率分别为23.0%和28.2%,较30～34岁和35岁以上组HPV感染率明显增高(P<0.01)。本组妇女CIN现患率为4.4%,CINⅠ现患率明显高于CINⅡ和CINⅢ(P<0.05)。社区居民、工厂工人和服务业妇女CIN现患率分别为3.8%、2.8%和7.4%,服务业妇女CIN现患率明显高于社区居民和工厂工人CIN(P<0.05)。随病变级别升高HPV感染率呈趋势性增加,CINⅡ以上HPV感染率为100%。工人CINⅠ和慢性宫颈炎的HPV感染率为40.0%和47.8%,而服务业CINⅠ的感染率是85.7%,慢性宫颈炎亦有66.7%HPV阳性。单因素和多因素非条件Logistic回归分析,HPV感染是CIN的唯一高危因素(χ2=133.751,P=0.000,OR=43.431);妇女职业、性伙伴≥3个和最经常性伙伴维持时间在1年以内等者是HPV感染的显著危险因素。结论:高危型HPV感染是本组CIN的主要原因,服务业30岁以下妇女HPV感染和CIN现患率均较高,应做重点监测。     

珠海地区妇女宫颈上皮内瘤变与高危型人乳头瘤病毒亚型关系的初步研究

目的探讨珠海地区妇女宫颈上皮内瘤变与高危型人乳头瘤病毒亚型的关系。方法采用杂交捕获二代（HC-Ⅱ）方法定量检测珠海地区宫颈疾病患者HPV-DNA的含量,全部269例患者阴道镜下多点取活组织病理检查,根据病理学诊断结果分组。结果珠海地区高危型HPV在慢性宫颈炎、C INⅠ、C INⅡ及C INⅢ的感染率分别为13.5%、48.2%、73.8%及93.7%,HPV16在四组中感染率依次为3.6%、13.4%、47.6%及65.6%,宫颈病变存在多重HPV感染。结论珠海地区宫颈上皮内瘤变患者感染HPV16、18、31、58及35型较多见,多重HPV感染可能促进宫颈上皮内瘤变的发生。     

Variant‐specific persistence of infections with human papillomavirus Types 31, 33, 45, 56 and 58 and risk of cervical intraepithelial neoplasia

In our previous study of the etiologic role of oncogenic human papillomavirus (HPV) types other than HPV16 and 18, we observed a significantly higher risk of cervical intraepithelial neoplasia Grades 2–3 (CIN2/3) associated with certain lineages of HPV types 31/33/45/56/58 [called high‐risk (HR) variants] compared with non‐HR variants. This study was to examine whether these intra‐type variants differ in persistence of the infection and persistence‐associated risk of CIN2/3. Study subjects were women who had any of HPV types 31/33/45/56/58 newly detected during a 2‐year follow‐up with 6‐month intervals. For each type, the first positive sample was used for variant characterization. The association of reverting‐to‐negativity with group of the variants and CIN2/3 with length of positivity was assessed using discrete Cox regression and logistic regression, respectively. Of the 598 newly detected, type‐specific HPV infections, 312 became undetectable during follow‐up. Infections with HR, compared with non‐HR, variants were marginally more likely to become negative [adjusted hazard ratio = 1.3; 95% confidence interval (CI), 0.9–1.8]. The adjusted odds ratio associating with the development of CIN2/3 was 3.0 (95% CI, 1.2–7.4) for persistent infections with HR variants for 6 months and 10.0 (95% CI, 3.8–38.0) for persistent infections with HR variants for 12–18 months as compared with the first positive detection of HR variants. Among women with non‐HR variants, there were no appreciable differences in risk of CIN2/3 by length of positivity. Findings suggest that the lineage‐associated risk of CIN2/3 was not mediated through a prolonged persistent infection, but oncogenic heterogeneity of the variants.     

Persistence of HPV infection and risk of high-grade cervical intraepithelial neoplasia in a cohort of Colombian women

Little is known about the dynamics of human papillomavirus (HPV) infection and subsequent development of high-grade cervical intraepithelial neoplasia (CIN2/3), particularly in women >30 years of age. This information is needed to assess the impact of HPV vaccines and consider new screening strategies. A cohort of 1728 women 15–85 years old with normal cytology at baseline was followed every 6 months for an average of 9 years. Women with squamous intraepithelial lesions were referred for biopsy and treatment. The Kaplan–Meier method was used to estimate the median duration of infection and Cox regression analysis was undertaken to assess determinants of clearance and risk of CIN2/3 associated with HPV persistence. No difference in the likelihood of clearance was observed by HPV type or woman''s age, with the exception of lower clearance for HPV16 infection in women under 30 years of age. Viral load was inversely associated with clearance. In conclusion, viral load is the main determinant of persistence, and persistence of HPV16 infections carry a higher risk of CIN2/3.     

Differences in human papillomavirus type distribution in high‐grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe

Knowledge of differences in human papillomavirus (HPV)‐type prevalence between high‐grade cervical intraepithelial neoplasia (HG‐CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV‐infected cervical lesions and the potential impact of HPV vaccination on cervical cancer prevention. More than 6,000 women diagnosed with HG‐CIN or ICC from 17 European countries were enrolled in two parallel cross‐sectional studies (108288/108290). Centralised histopathology review and standardised HPV‐DNA typing were applied to formalin‐fixed paraffin‐embedded cervical specimens dated 2001–2008. The pooled prevalence of individual HPV types was estimated using meta‐analytic methods. A total of 3,103 women were diagnosed with HG‐CIN and a total of 3,162 with ICC (median ages: 34 and 49 years, respectively), of which 98.5 and 91.8% were HPV‐positive, respectively. The most common HPV types in women with HG‐CIN were HPV16/33/31 (59.9/10.5/9.0%) and in ICC were HPV16/18/45 (63.3/15.2/5.3%). In squamous cell carcinomas, HPV16/18/33 were most frequent (66.2/10.8/5.3%), and in adenocarcinomas, HPV16/18/45 (54.2/40.4/8.3%). The prevalence of HPV16/18/45 was 1.1/3.5/2.5 times higher in ICC than in HG‐CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/‘other’ (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/‘other’ (15/23/20/17 years). In Europe, HPV16 predominates in both HG‐CIN and ICC, whereas HPV18/45 are associated with a low median age of ICC. HPV18/45 are more frequent in ICC than HG‐CIN and associated with a high median age of HG‐CIN, with a narrow age interval between HG‐CIN and ICC detection. These findings support the need for primary prevention of HPV16/18/45‐related cervical lesions.     

The role of human papillomavirus type 16/18 genotyping in predicting high‐grade cervical/vaginal intraepithelial neoplasm in women with mildly abnormal Papanicolaou results

BACKGROUND:

The authors compared the predictive value of type 16 and/or 18 human papillomavirus (HPV) versus non‐16/18 HPV types for high‐grade (grade ≥2) cervical neoplasm/vaginal intraepithelial neoplasm and carcinoma (CIN/VAIN2+) in women with mildly abnormal Papanicolaou (Pap) results (ie, atypical squamous cells of undetermined significance [ASCUS] or low‐grade squamous epithelial lesion [LSIL]).

METHODS:

The authors retrospectively selected Pap specimens with HPV testing results obtained from 243 women (155 with ASCUS and 88 with LSIL Pap results) in their Department of Pathology. HPV genotyping was performed using the EasyChip HPV blot assay. The Pap specimens with HPV16/18 and non‐16/18 HPV types were compared with follow‐up biopsy results. Follow‐up duration ranged from 1 month to 58 months (mean, 26 months).

RESULTS:

In total, 58 of 155 specimens (37%) that had ASCUS and 29 of 88 specimens (33%) that had LSIL were positive for HPV16/18. CIN/VAIN2+ biopsies were identified in 43 of 155 women (28%) with ASCUS and in 28 of 88 women (32%) with LSIL. Women with ASCUS and HPV16/18 had a significantly higher rate (43%) of CIN/VAIN2+ than women with ASCUS and non‐16/18 HPV types (19%; P = .003; odds ratio, 3.10; 95% confidence interval, 1.48‐6.53). There was no statistically significant difference in the rate of CIN/VAIN2+ between women who had LSIL and HPV16/18 (45%) and those who had LSIL and non‐16/18 HPV types (29%; P = .16; odds ratio, 1.96; 95% confidence interval, 0.77‐4.97).

CONCLUSIONS:

HPV genotyping for HPV16/18 improved risk assessment for women with ASCUS Pap results and may be used to predict the risk of CIN/VAIN2+ to better guide follow‐up management. Cancer (Cancer Cytopathol) 2013. © 2012 American Cancer Society.     

Prevalence of human papillomavirus and cervical intraepithelial neoplasia in China: A pooled analysis of 17 population-based studies

High-risk (HR) human papillomavirus (HPV) prevalence has been shown to correlate well with cervical cancer incidence rates. Our study aimed to estimate the prevalence of HR-HPV and cervical intraepithelial neoplasia (CIN) in China and indirectly informs on the cervical cancer burden in the country. A total of 30,207 women from 17 population-based studies throughout China were included. All women received HPV DNA testing (HC2, Qiagen, Gaithersburg, MD), visual inspection with acetic acid and liquid-based cytology. Women positive for any test received colposcopy-directed or four-quadrant biopsies. A total of 29,579 women had HR-HPV testing results, of whom 28,761 had biopsy confirmed (9,019, 31.4%) or assumed (19,742, 68.6%) final diagnosis. Overall crude HR-HPV prevalence was 17.7%. HR-HPV prevalence was similar in rural and urban areas but showed dips in different age groups: at age 25–29 (11.3%) in rural and at age 35–39 (11.3%) in urban women. In rural and urban women, age-standardized CIN2 prevalence was 1.5% [95% confidence interval (CI): 1.4–1.6%] and 0.7% (95% CI: 0.7–0.8%) and CIN3+ prevalence was 1.2% (95% CI: 1.2–1.3%) and 0.6% (95% CI: 0.5–0.7%), respectively. Prevalence of CIN3+ as a percentage of either all women or HR-HPV-positive women steadily increased with age, peaking in 45- to 49-year-old women. High prevalence of HR-HPV and CIN3+ was detected in both rural and urban China. The steady rise of CIN3+ up to the age group of 45–49 is attributable to lack of lesion removal through screening. Our findings document the inadequacy of current screening in China while indirectly raising the possibility that the cervical cancer burden in China is underreported.     

人乳头瘤病毒亚临床感染和宫颈上皮内瘤变的电子阴道镜和病理学观察

目的探讨电子阴道镜(EC)检查对宫颈人乳头瘤病毒亚临床感染(SPI)和宫颈上皮内瘤样变(CIN)的诊断价值及其与病理诊断的一致性。方法1420例在EC下筛查,对209例拟诊病例观察其EC图像,行宫颈活检病理学和HPV-6、11、18型免疫组化检查。结果SPI和CIN的EC图像主要是不同程度的醋酸白色上皮、血管异常改变和碘阴性染色。HPV感染的病理组织学特征是挖空细胞形成,这种病变在大部分的SPI和CIN患者中被发现(62例,74.6%)。病理形态学结合免疫组化诊断SPI56例(26.79%),CINⅠ10例(4.78%),CINⅡ9例(4.31%),CINⅢ8例(3.83%),宫颈炎126例(60.29%)。HPV-6、11、18型免疫组化的总检出率为23%(48/209)。EC诊断SPI、CIN和慢性宫颈炎与病理诊断的一致率(准确度)为88.04%(184/209,Kappa=0.755,P<0.01),灵敏度90.36%(75/83),特异度86.51%(109/126),阳性预测值81.52%(75/92),阴性预测值93.16%(109/117),两种检查结果比较差异无显著性(P>0.05)。结论EC是一种有效可靠的诊断宫颈病变的筛查方法,在EC下取活检结合免疫组织化学能提高SPI和CIN的早期诊断率。     

Long‐term risk of cervical cancer following conization of cervical intraepithelial neoplasia grade 3—A Danish nationwide cohort study

Using nationwide Danish registries we examined the long‐term risk of cervical cancer in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) (including adenocarcinoma in situ (AIS)) on the cone compared to women with a normal cytology test. Initially, we identified women born 1918–1990, who were recorded as living in Denmark between January 1, 1978 and December 31, 2012. From the Pathology Data Bank information on CIN3 on the cone, margins status, histological type of CIN3 and cervical cytology results was extracted. Cox proportional hazard model was used to estimate the relative risk of subsequent cervical cancer. We included 59,464 women with CIN3 on the cone and 1,918,508 women with a normal cytology test. Overall, women diagnosed with CIN3 had a higher risk of subsequent cervical cancer compared to women with normal cytology (HR = 2.06; 95%CI: 1.81–2.35). Analyses according to time since conization showed elevated risks in all time periods, and 25 years or more after conization the relative risk was significantly increased (HR = 2.56; 95%CI: 1.37–4.77). Twenty years or more after conization, also women with negative margins had an increased relative risk (HR = 2.49; 95%CI: 1.12–5.57). In addition, the long‐term relative risk of cervical cancer varied with the different histological types of CIN3 and was highest for AIS (HR = 7.50; 95%CI: 1.87–30.01, 10–14 years after conization). In conclusion, women diagnosed with CIN3 on the cone have a long‐lasting increased risk of cervical cancer even when the margins on the cone are negative.     

Condom use promotes regression of cervical intraepithelial neoplasia and clearance of human papillomavirus: a randomized clinical trial

Women with persistent HPV infections have increased risk of progressive CIN lesions. Transmission of HPV between sexual partners might maintain viral infection and, consequently, may influence the clinical course of CIN. We investigated the effect of condom use on regression of CIN lesions and on clearance of HPV. Women with CIN and their male sexual partners were randomized for condom use (condom group n = 72 and noncondom group n = 76). They were conservatively managed and followed every 3-6 months by colposcopy, cytology and HPV testing by GP5+/6+ PCR. Baseline cervical biopsy specimens were taken. Median follow-up time for women was 15.2 months (range 3.0-85.4). Outcomes of interest were clinical regression of CIN at colposcopy and clearance of HPV. Outcomes were assessed in 64 women of the condom group and 61 women of the noncondom group. Women in the condom group showed a 2-year cumulative regression rate of 53% vs. 35% in the noncondom group (p = 0.03). The 2-year cumulative rates of HPV clearance were 23% vs. 4%, respectively (p = 0.02). Although lower regression rates were found if women were HPV-positive and had > or =CIN2 lesions at baseline, effects of condom use were found both in women with CIN1 and in women with > or =CIN2 lesions. Condom use promotes regression of CIN lesions and clearance of HPV.     

子宫颈上皮内瘤变的高危型HPV负荷量对治疗后复发的影响

目的 探讨术前子宫颈上皮内瘤变(CIN)的高危型人乳头瘤病毒(HR-HPV)的负荷量与CIN治疗后复发的关系.方法 选择205例CIN患者,术前均采用第二代杂交捕获法(hybrid captureⅡ,HC-Ⅱ)检测HPV负荷量,术后6-8月于阴道镜下行子宫颈活检病理检查.结果 术前HR-HPV负荷量与CIN呈等级正相关(r=0.4288,P＜0.01),经6-8月随访,发现25例CIN复发,其术前HR-HPV负荷量均＞1 000 RLU/CO,术后CIN复发与术前HR-HPV负荷高负荷量有关(P＜0.01),与术前CIN级别无关(P＜0.01).结论 C1N术前HR-HPV高负荷量(＞1 000 RLU/CO)可增加术后CIN复发的危险性.     

Viral load as a predictor of the risk of cervical intraepithelial neoplasia

HPV infections are believed to be a necessary cause of cervical cancer. Viral burden, as a surrogate indicator for persistence, may help predict risk of subsequent SIL. We used results of HPV test and cytology data repeated every 4–6 months in 2,081 women participating in a longitudinal study of the natural history of HPV infection and cervical neoplasia in São Paulo, Brazil. Using the MY09/11 PCR protocol, 473 women were positive for HPV DNA during the first 2 visits. We retested all positive specimens by a quantitative, low‐stringency PCR method to measure viral burden in cervical cells. Mean viral loads and 95% CIs were calculated using log‐transformed data. RRs and 95% CIs of incident SIL were calculated by proportional hazards models, adjusting for age and HPV oncogenicity. The risk of incident lesions increased with viral load at enrollment. The mean number of viral copies/cell at enrollment was 2.6 for women with no incident lesions and increased (trend p = 0.003) to 15.1 for women developing 3 or more SIL events over 6 years of follow‐up. Compared to those with <1 copy per cell in specimens tested during the first 2 visits, RRs for incident SIL increased from 1.9 (95% CI 0.8–4.2) for those with 1–10 copies/cell to 4.5 (95% CI 1.9–10.7) for those with >1,000 copies/cell. The equivalent RR of HSIL for >1,000 copies/cell was 2.6 (95% CI 0.5–13.2). Viral burden appears to have an independent effect on SIL incidence. Measurement of viral load, as a surrogate for HPV persistence, may identify women at risk of developing cervical cancer precursors. © 2002 Wiley‐Liss, Inc.