Human papillomavirus genotype distribution and cervical squamous intraepithelial lesions among high-risk women with and without HIV-1 infection in Burkina Faso

Human papillomavirus (HPV) infection and cervical squamous intraepithelial lesions (SILs) were studied in 379 high-risk women. Human papillomavirus DNA was detected in 238 of 360 (66.1%) of the beta-globin-positive cervical samples, and 467 HPV isolates belonging to 35 types were identified. Multiple (2-7 types) HPV infections were observed in 52.9% of HPV-infected women. The most prevalent HPV types were HPV-52 (14.7%), HPV-35 (9.4%), HPV-58 (9.4%), HPV-51 (8.6%), HPV-16 (7.8%), HPV-31 (7.5%), HPV-53 (6.7%), and HPV-18 (6.4%). Human immunodeficiency virus type 1 (HIV-1) seroprevalence was 36.0%. Human papillomavirus prevalence was significantly higher in HIV-1-infected women (87 vs 54%, prevalence ratio (PR) = 1.61, 95% confidence interval (CI): 1.4-1.8). High-risk HPV types (71 vs 40%, PR = 1.79, 95% CI: 1.5-2.2), in particular HPV-16+18 (22 vs 9%, PR = 2.35, 95% CI: 1.4-4.0), and multiple HPV infections (56 vs 23%, PR = 2.45, 95% CI: 1.8-3.3) were more prevalent in HIV-1-infected women. High-grade SIL (HSIL) was identified in 3.8% of the women. Human immunodeficiency virus type 1 infection was strongly associated with presence of HSIL (adjusted odds ratio = 17.0; 95% CI 2.2-134.1, P = 0.007) after controlling for high-risk HPV infection and other risk factors for HSIL. Nine of 14 (63%) HSIL cases were associated with HPV-16 or HPV-18 infection, and might have been prevented by an effective HPV-16/18 vaccine.     

Human Papillomavirus Infection and Risk Determinants for Squamous Intraepithelial Lesion and Cervical Cancer in Japan

A case control design was used to investigate human papillomavirus (HPV) prevalence and risk factors associated with development of cervical squamous intraepithelial lesion (SIL) and cervical cancer (CC) in Japan, One hundred and twenty-three women with histologically confirmed SIL or CC were compared to a control group of 778 cytologically normal women. With the use of a polymerase chain reaction (FCR)-hased method for detection of low-risk (types 6 and 11) and high-risk (types 16, 18, 31, 33, 35, 52 and 58) HPVs, a high prevalence of HPV infection was observed in smokers among the controls. Logistic regression analysis demonstrated that high-risk HPV infection was the most significant risk determinant for LSIL (OR=9.4, 95% CI=4.5–19), HSIL (OR=77, 95% CI=28–217) and CC (OR=97, 95% CI=35–269). It also showed that unmarried women, women married for 5 to 19 years and smokers represented high risk groups for SIL, while smokers and women with a history of many pregnancies/parities had increased risk for CC. Smoking was the only HPV infection-independent factor for CC, suggesting that smoking may have a carcinogenic effect on the cervix. Since neither history of other cancer nor family cancer history was associated with SIL or CC, genetic factors appear to play little role in cervical carcinogenesis. The risk for cervical neoplasia due to HPV infection increased after marriage in Japan, suggesting a role for husbands as carriers of HPV transmission. Protection from high-risk HPV infection may be of greatest importance for prevention of cervical cancer.     

Viral load of episomal and integrated forms of human papillomavirus type 33 in high-grade squamous intraepithelial lesions of the uterine cervix

The association between total and integrated HPV-33 DNA loads and high-grade squamous intraepithelial lesions (HSIL) of the uterine cervix was investigated. Of 5,347 women recruited in 4 studies, 89 (64 without SIL, 7 low-grade SIL (LSIL), 15 HSIL, 3 unknown grade) were infected by HPV-33. HPV-33 E6, HPV-33 E2 and beta-globin DNA were measured with real-time PCR that allowed to assess total (E6), episomal (E2) and integrated (E6-E2) HPV-33 viral loads. HPV-33 E6/E2 ratios >/=>/=2.0 suggesting the presence of integrated HPV-33 were obtained for 28.6% (n = 18) of women without SIL and 21.4% (n = 3) of women with HSIL (p = 0.74). Although median viral loads were similar, there was a trend toward having a greater proportion of women with HSIL in the fourth quartile (>/=>/=10(6.69) copies/mug DNA) of total HPV-33 viral loads compared to normal women. Controlling for age, site, ethnicity and LCR polymorphism by logistic regression, HPV-33 total loads in the fourth quartile {odds ratio (OR) 4.5 [95% confidence interval (CI) 1.2-17.3]; p = 0.03} and episomal loads in the fourth quartile (>/=>/=10(6.64) copies/mug DNA) [OR 3.9 (95% CI 1.1-13.2); p = 0.05] but not integrated HPV-33 load in the fourth quartile [OR 1.0 (95% CI 0.3-3.3); p = 0.50] were associated with HSIL. Controlling for age, study site and SIL grade, HPV-33 episomal load [OR 0.2 (95% CI 0.1-0.5), p = 0.0004] was associated with the presence of HPV-33 integration. High episomal loads in HSIL and the presence of integration in women without SIL are likely to weaken the usefulness of HPV load of integrated forms in clinical practice.     

High-risk and multiple human papillomavirus infections associated with cervical abnormalities in Japanese women.

To estimate the risk of human papillomavirus (HPV) infection for cervical malignancies, we conducted a case-control study in Japan. Abnormal cervical cell (366) and normal cell samples (1562) were tested for the presence of HPV DNA using a new PCR-based test (LCR-E7 PCR). When single HPV infections were considered, 26 different HPV types were identified in normal cervices and in low-grade squamous intraepithelial lesions (LSIL); whereas HPV-16, -18, -31, -33, -35, -45, -51, -52, -56, -58 and -67 were detected in high-grade squamous intraepithelial lesions (HSIL) and in squamous cell carcinoma (SCC) of the cervix, and HPV-16 and -18 were detected in cervical adenocarcinoma. HPV-6 and -11 were detected in condyloma acuminatum tissue. In HSIL and SCC, HPV-16 was the most prevalent type and HPV-51, -52, and -58 were the next most prevalent; whereas HPV-39, -59, and -68 were not detected. Analysis by odds ratio (OR) revealed that HPV-11, -39, -42, -44, -53, -59, -62, and -66 (HPV-66: OR,139; 95% confidence interval (CI) = 6.7-168) were associated with LSIL; HPV-16, -18, -31, -51, -52 and -58 (HPV-16: OR, 69; 95%CI = 36-131) were associated with SCC; and HPV-16 and -18 (OR, 94; 95% CI = 28-317) were associated with adenocarcinoma. Multiple HPV infection was associated with LSIL (OR, 24; 95%CI = 13-44), HSIL (OR, 16; 95%CI = 8.4-32), and SCC (OR, 8.3; 95%CI = 3.2-22), although the prevalence decreased with the grade of the lesions. All results suggest that HPV-6 and -11 are condyloma types, HPV-16, -18, -31, -51, -52, -58, and perhaps -33, -35, -45, -56, and -67, are the high-risk HPV types, and many other types are LSIL-associated types in Japan. HPV typing and detection of multiple HPV infections in clinical samples may be useful as surrogate markers for cervical cell abnormalities.     

High grade cervical lesions are caused preferentially by non-European variants of HPVs 16 and 18

The intratypic variability of HPVs 16 and 18 has been extensively studied and has been used as an important tool in epidemiological studies of viral transmission, persistence and progression to clinically relevant cervical lesions. Infections by non-European variants of HPVs 16 and 18 are associated with an increased risk for the development of high grade squamous intraepithelial lesions (HSIL). Our aim was to correlate the intratypic molecular variability of both HPV types and risk of persistent infection and lesion outcome in a cohort study conducted in Brazil. We characterized molecular variants of HPV types 16 and 18 by sequencing a fragment of the LCR, and of the E6 and L1 genes, for HPV-16 variants only. For both types, European variants composed the most prevalent and diverse group. Persistent infections with HPV-18 were associated with continuous detection of European variants. However, risk for simultaneous detection of HSIL and HPV DNA was higher in women harboring non-European variants of HPV-16. The same trend was observed with HSIL detected during follow-up. Our study confirms the association between non-European variants and risk of cervical neoplasia, and highlights the importance of their geographic distribution for cervical cancer risk assessment.     

Human papillomavirus infection and other risk factors for cervical neoplasia: a case-control study

A case control design has been used to investigate risk factors associated with the development of cervical squamous intraepithelial lesions (SIL) in a population of urban women in which non-affluent minority groups were heavily represented. Eighty-five women with histologically confirmed SIL were compared to a control group of 70 cytologically normal women. HPV infection was determined using both Southern blot hybridization and polymerase chain reaction (PCR) amplification specific for HPV types 16, 18, and 33. When Southern blot was used to detect HPV, logistic regression analysis identified HPV infection (odds ratio (OR) = 17.9, 95% confidence interval (CI) = 6.2-51.6) and low educational achievement (OR = 3.4, 95% CI = 1.2-10.1) as major independent risk factors. When PCR was employed to detect HPV, the logistic regression model suggested that HPV infection (OR = 10.4, 95% CI = 3.6-30.4) and Hispanic ethnicity (OR = 5.0, 95% CI = 1.2-20.5) represented independent risk factors; low educational achievement and Black ethnicity were risk factors of borderline significance. PCR detection of simultaneous co-infection with more than one HPV type was associated with a very high risk of SIL (OR for one type = 7.2, 95% CI = 2.4-21.9; OR for greater than I type = 43.0, 95% CI = 6.9-266.6). Furthermore, increased viral load determined by either method carried an increased risk of disease. HPV infection with viral types previously reported to be related to neoplastic or dysplastic lesions carried the highest risk of SIL. The association of HPV detected by Southern blot and SIL in women less than 35 years old had an OR of 10.1, whereas in women greater than or equal to 35 the OR was 74.5 (p = 0.09 for homogeneity of ORs). We conclude that infection with HPV is the major risk factor for cervical SIL and suggest that targeted HPV screening of women over age 35 may represent an innovative strategy to detect women at high risk of cervical neoplasia.     

Human papillomavirus genotypes and HPV-16 variants distribution among Tunisian women with normal cytology and squamous intraepithelial lesions

Background

Little is known about the epidemiological characteristics of papillomavirus (HPV) infection among North African countries. Herein, we conducted a molecular epidemiological study to investigate prevalence of HPV type and HPV-16 variants among cervical-screened unvaccinated Tunisian women.

Methods

Cross-sectional study was performed on 494 Tunisian women visiting Women’s Healthcare Centers. HPV-DNA detection was carried out on cervical samples using real-time polymerase chain reaction. HPV genotyping and HPV-16 variants were characterized by direct sequencing of L1 viral capsid gene.

Results

The overall HPV prevalence was 34% (95% CI: 30–38%) with significantly higher prevalence among women with squamous intraepithelial lesions (SIL) than those with no intraepithelial lesions (NIL) 84% (95% CI: 76–92%) and 24.5% (95% CI: 20–29%) respectively. The distribution of HPV prevalence according to women’s age shows a U-shaped curve and the highest HPV prevalence rates were observed among the youngest (≤25 years; 51.2%, 95% CI: 37–67%) and the oldest women (>55 years; 41.7%, 95% The HPV-16 prevalence was 32.8% (95% CI: 22–45%) among women with SIL and 9.2% (95% CI: 6–12%) among women with NIL. Whereas, the HPV-18 prevalence was 1.3% (95% CI: 0–5%) among women with SIL and 0.3% (95% CI: 0–1%) among women with NIL. Among HPV-16 positive women, European lineage (E) was identified as the predominant HPV-16 variant (85.7%, 95% CI: 76–95%). The frequency of E variant was lower among SIL than among NIL women (81%, 95% CI: 64–99%, and 88%, 95% CI: 77–100%, respectively). Conversely, the African-2 variant frequency was higher among SIL than among NIL women (18%, 95% CI: 1–36% and 6%, 95% CI: 2–14%, respectively). In multivariate analysis, young age was the only risk factor that is independently associated with HPV infection. Moreover, HPV infection and menopause were both found to be independently associated with SIL and HSIL.

Conclusion

HPV DNA testing should be proposed to young and menopausal Tunisian women. Considering HPV prevalence, only 13% of the Tunisian women could be protected by the bivalent HPV vaccine. These results may be helpful for designing an adapted HPV testing and vaccination program in Tunisia.

     

Characterization of HPV genotype profile in squamous cervical lesions in Portugal, a southern European population at high risk of cervical cancer.

A different prevalence of human papillomavirus (HPV) types has been reported in distinct populations. Although Portugal has a relatively high incidence of cervical cancer within the European Union, no studies have been reported in the Portuguese population. Recently, a clinical trial using a vaccine targeted against HPV-16 demonstrated a high efficacy in preventing HPV-16 cervical lesions. The aim of the present study was the characterization of HPV genotype profile in squamous intraepithelial lesions (SIL) and invasive cervical cancer (ICC) from 608 patients using polymerase chain reaction (PCR) methodology. We frequently detected HPV-6/11 and HPV-16 in low-grade SIL (HPV-6/11, 18.9%; HPV-16, 44.2%). In high-grade SIL, HPV-16 was demonstrated in 74.2% of those lesions and in 80.0% of the cases with ICC. HPV-18 was found in 3.1%, 0.8% and in 15.0% of low, high SIL and ICC, respectively. The overall prevalence of multiple infections with high-risk HPV was 7.2%. Other types of HPV were detected in 7.0% of all cases. Our results demonstrate a high prevalence of HPV-16 in SIL and ICC in Portuguese women. Therefore, a prophylactic HPV-16/18 vaccine may be effective in the prevention of cervical cancer in a significant number of women from this southern European population.     

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.     

Prevalence of specific types of human papillomavirus and cervical squamous intraepithelial lesions in consecutive,previously unscreened,West-African women over 35 years of age

Previous studies among women worldwide have demonstrated that infection with specific types of human papillomaviruses (HPV) is central to the pathogenesis of cervical neoplasia. There is little data, however, concerning the prevalence of specific HPV types and the association of each type with cervical neoplasia among women in sub-Saharan Africa, who remain at very high risk of cervical cancer. We studied 2,065 consecutive patients aged 35 years or older, presenting to community health clinics in Dakar and Pikine, West Africa, who had not been screened previously for cytologic abnormalities or HPV. Cytologic diagnosis and HPV detection were accomplished using a ThinPrep Pap and a polymerase chain reaction-based reverse-line strip assay, respectively. Odds ratios (OR) and associated 95% confidence intervals (CI) were estimated using polynomial logistic regression. Cytologic abnormalities were found in 426 women (20%), including 254 (12%) with atypical squamous cells of undetermined significance, 86 (4%) with low-grade squamous intraepithelial lesions, 66 (3%) with high-grade squamous intraepithelial lesions (HSIL) and 20 (1%) with invasive cancer. HPV infection was detected in 18%. Among women with negative cytologic findings, the prevalence of high risk but not low risk HPV types increased with age. HPV16 (2.4%) and HPV58 (1.6%) were the most frequently detected HPV types in this population, as well as being the most strongly associated with risk of HSIL/cancer (HPV16: OR = 88, 95% CI = 39-200; HPV58: OR = 51, 95% CI = 16-161). These data suggest that in addition to HPV16, HPV58 should be considered in the strategic planning of vaccination against cervical cancer in this geographic region.     

Variability of high risk HPV genotypes among HIV infected women in Mwanza,Tanzania- the need for evaluation of current vaccine effectiveness in developing countries

Background

High risk (HR) human papilloma Virus (HPV) genotypes have been associated with cervical cancer. In Tanzania there is a limited data on the epidemiology of HPV and genotypes distribution among HIV infected women. Here we document varieties of HPV genotypes associated with cervical squamous intraepithelial lesions (SIL) among HIV- infected women at Bugando Medical Centre, Mwanza-Tanzania.

Methods

A cross sectional hospital based study involving HIV infected women was conducted between August and October, 2014. Exfoliated cells from ectocervix and endocervix were collected using cytobrush. HPV genotypes were detected using polymerase chain reaction (PCR) followed by sequencing using specific primers targeting broad range of HPV types. Cytology was done to establish squamous intraepithelial lesions. Log binomial regression analysis was done to establish risk ratios (RR) associated with HPV infection using STATA version 11.

Results

A total of 255 HIV infected women with mean age 39.2?±?9.1 years were enrolled in the study. HPV DNA was detected in 138/255 (54.1 %, 95 % CI: 47-60) of HIV infected women. Twenty six genotypes were detected in various combinations; of these 17(65.3 %) were of HR genotypes. HR genotypes were detected in 124(48.6 %) of HIV infected women. Common HR genotypes detected were HPV-52(26), HPV-58(21), HPV-35(20) and HPV-16(14). The risk of being HPV positive was significantly higher among women with CD4 counts <100 (RR: 1.20, 95 % CI: 1.05-1.35, P?=?0.006) and women with SIL (RR: 1.37, 95 % CI: 1.11-1.68, P?=?0.005)

Conclusion

Significant proportion of HIV infected women with low CD4 counts have various grades of cervical SIL associated with varieties of uncommon HR genotypes. There is a need to evaluate the effectiveness of the current vaccine in preventing cervical cancer in developing countries where HIV is endemic.

     

Detection of human papillomavirus DNA in cytologically normal women and subsequent cervical squamous intraepithelial lesions.

BACKGROUND: Human papillomavirus (HPV) infection has been strongly associated with cervical carcinoma and its cytologic precursors, squamous intraepithelial lesions (SIL). We investigated the risk of SIL prospectively following polymerase chain reaction (PCR)-based DNA testing for a wide range of genital HPV types in a cohort of initially cytologically normal women, to clarify the role of HPV in the etiology of SIL. METHODS: Starting in April 1989, 17,654 women who were receiving routine cytologic screening at Kaiser Permanente (Portland, OR) were followed for the development of incident SIL. During follow-up, 380 incident case patients and 1037 matched control subjects were eligible for this nested case-control study. Cervical lavages collected at enrollment and, later, at the time of case diagnosis (or the corresponding time for selection of control subjects) were tested for HPV DNA using a PCR-based method. The data were analyzed as contingency tables with two-sided P values or, for multivariable analyses, using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In comparison with initially HPV-negative women, women who tested positive for HPV DNA at enrollment were 3.8 times (95% CI = 2.6-5.5) more likely to have low-grade SIL subsequently diagnosed for the first time during follow-up and 12.7 times more likely (95% CI = 6.2-25.9) to develop high-grade SIL. At the time of diagnosis, the cross-sectional association of HPV DNA and SIL was extremely strong (OR = 44.4 and 95% CI = 24.2-81.5 for low-grade SIL and OR = 67.1 and 95% CI = 19.3-233.7 for high-grade SIL). HPV16 was the virus type most predictive of SIL, even low-grade SIL. CONCLUSIONS: These findings are consistent with the hypothesis that HPV infection is the primary cause of cervical neoplasia. Furthermore, they support HPV vaccine research to prevent cervical cancer and efforts to develop HPV DNA diagnostic tests.     

汕头市妇女HPV-52感染与宫颈鳞状上皮病变的关系

目的： 探讨汕头市妇女感染人乳头状瘤病毒（HPV）的主要亚型,及其在宫颈鳞状上皮病变中的致病特点及风险分析。方法： 收集2015~2018年在汕头市中心医院同时进行HPV分型检测和薄层液基细胞学（LCT）检查的病例37 700例,及其中3 924例进行宫颈活检的病例。HPV分型检测采用医用核酸分子快速杂交基因分型试剂盒,包含15种高危HPV,即HPV-16、-18、-31、-33、-35、-39、-45、-5l、-52、-53、-56、-58、-59、-66和-68;6种低危型HPV,即HPV-6、-11、-42、-43、-44、CP8304。细胞学检查按照伯塞斯达系统（TBS）分级（2014版）标准进行分类,分为未见上皮内病变或恶性病变（NILM）、非典型鳞状细胞-意义不明确（ASC-US）、低级别鳞状上皮内病变（LSIL）、非典型鳞状细胞-不排除高级别鳞状上皮内病变（ASC-H）、高级别鳞状上皮内病变（HSIL）和鳞状细胞癌（SCC）。使用SPSS 19.0软件建立数据库,计数资料率的比较采用频数分布进行统计,风险评估采用卡方检验2×2列表。结果： 37 700位LCT检查病例中HPV-52总感染率为3.55%（1 338/37 700）,HPV-52单一感染882例,HPV-52多重感染（指两种及以上HPV亚型感染）456例,其中包含两重感染313例,三重及以上感染143例,HPV-52多重感染最常见的3种亚型分别是HPV-58/52（12.46%,39/313）、HPV-53/52（11.18%,35/313）、HPV-16/52（11.18%,35/313）。HPV-52多重感染患者LCT筛查结果出现ASC-US及以上病变尤其是HSIL中,最多见型别为HPV-16/52。宫颈活检结果风险分析显示,与HPV-52单一感染比较,HPV-52/16多重感染患HSIL/SCC风险增加（P < 0.01,OR=8.27）,并且增加HSIL发展到SCC的发病风险（P=0.01,OR=12.65）。与包含HPV-52但不包含HPV-16的多重感染比较,HPV-52/16多重感染增加患HSIL或者SCC风险（P < 0.01,OR=3.36）,并且增加HSIL发展为SCC的风险（P=0.03,OR=1.29）。结论： HPV-52是汕头市妇女最常见的HPV感染宫颈亚型,但患者主要发生HSIL病变,当合并HPV-16感染时增加癌前病变及癌变风险。     

汕头市妇女HPV-52感染与宫颈鳞状上皮病变的关系

目的： 探讨汕头市妇女感染人乳头状瘤病毒（HPV）的主要亚型，及其在宫颈鳞状上皮病变中的致病特点及风险分析。方法： 收集2015~2018年在汕头市中心医院同时进行HPV分型检测和薄层液基细胞学（LCT）检查的病例37 700例，及其中3 924例进行宫颈活检的病例。HPV分型检测采用医用核酸分子快速杂交基因分型试剂盒，包含15种高危HPV，即HPV-16、-18、-31、-33、-35、-39、-45、-5l、-52、-53、-56、-58、-59、-66和-68；6种低危型HPV，即HPV-6、-11、-42、-43、-44、CP8304。细胞学检查按照伯塞斯达系统（TBS）分级（2014版）标准进行分类，分为未见上皮内病变或恶性病变（NILM）、非典型鳞状细胞-意义不明确（ASC-US）、低级别鳞状上皮内病变（LSIL）、非典型鳞状细胞-不排除高级别鳞状上皮内病变（ASC-H）、高级别鳞状上皮内病变（HSIL）和鳞状细胞癌（SCC）。使用SPSS 19.0软件建立数据库，计数资料率的比较采用频数分布进行统计，风险评估采用卡方检验2×2列表。结果： 37 700位LCT检查病例中HPV-52总感染率为3.55%（1 338/37 700），HPV-52单一感染882例，HPV-52多重感染（指两种及以上HPV亚型感染）456例，其中包含两重感染313例，三重及以上感染143例，HPV-52多重感染最常见的3种亚型分别是HPV-58/52（12.46%，39/313）、HPV-53/52（11.18%，35/313）、HPV-16/52（11.18%，35/313）。HPV-52多重感染患者LCT筛查结果出现ASC-US及以上病变尤其是HSIL中，最多见型别为HPV-16/52。宫颈活检结果风险分析显示，与HPV-52单一感染比较，HPV-52/16多重感染患HSIL/SCC风险增加（P < 0.01，OR=8.27），并且增加HSIL发展到SCC的发病风险（P=0.01，OR=12.65）。与包含HPV-52但不包含HPV-16的多重感染比较，HPV-52/16多重感染增加患HSIL或者SCC风险（P < 0.01，OR=3.36），并且增加HSIL发展为SCC的风险（P=0.03，OR=1.29）。结论： HPV-52是汕头市妇女最常见的HPV感染宫颈亚型，但患者主要发生HSIL病变，当合并HPV-16感染时增加癌前病变及癌变风险。     

Distribution and prevalence of human papillomavirus genotypes in routine pap smear of 2,470 korean women determined by DNA chip.

PURPOSE: We examined human papillomavirus (HPV) genotype distribution and prevalence from routine Pap smear cases in Korean women using DNA Chip.Patients and METHODS: A total of 2,470 cervical specimens from women attending routine Pap smear cytology screening in local hospitals was subjected to HPV test. HPV detection and genotyping were done using DNA Chip.RESULTS: HPV DNA was detected in 44.8% of the patients and in 58.7% of the 861 atypical lesions based on the Bethesda system, including 52.6% of 627 atypical squamous cells of undetermined significance (ASCUS), 69.0% of 168 low-grade squamous intraepithelial lesions (LSIL), and 89.4% of 66 high-grade squamous intraepithelial lesions (HSIL) cases. The most frequently found genotypes in all HPV-positive cases were HPV-16, HPV-52, and HPV-58. HPV-16 was the most prevalent type in within normal limits, ASCUS, and HSIL categories, whereas HPV-51 was most frequently found in LSIL. Multiple infection was identified in about 20% of HPV-positive cases and most of them were that by two different types. HPV-16 was present in the majority of multiple infection cases. A significant decrease in the percentage of multiple infection was observed in HSIL cases compared with ASCUS and LSIL.CONCLUSIONS: The distribution of HPV genotypes in Korean women was revealed to have differences to that of other regions, showing higher frequencies of HPV-52, HPV-58, and HPV-51. HSIL cases were mostly infected by sole HPV-16 whereas LSIL that by various HPV types, suggesting a certain type may become dominant over others as the disease progresses.     

Tobacco smoking and chewing as risk factors for multiple human papillomavirus infections and cervical squamous intraepithelial lesions in two countries (Côte d’Ivoire and Finland) with different tobacco exposure

Our objective was to compare the association between tobacco smoking and chewing and the risk of multiple human papillomavirus (HPV) infections and cervical squamous intraepithelial lesions (SILs) in two populations with different tobacco exposure. We studied 2,162 women from Côte d’Ivoire, West Africa, and 419 women from Finland, Northern Europe, with baseline data on cervical screening, HPV DNA status and smoking and chewing habits. The proportion of women who smoked and/or chewed tobacco was higher in Finland (36.8%) than in Côte d’Ivoire (3.7%), where tobacco chewing (2.6%) was more common than tobacco smoking (1.4%). Having multiple HPV infections was common in HPV16 and/or 18-infected women (60.4% in Finland and 47.2% in Côte d’Ivoire). There was no increased risk of multiple HPV infections among tobacco consumers. We found that women ≥30 years of age exposed to tobacco through smoking in Finland (OR: 2.2, 95% CI: 0.5–8.7) and chewing in Côte d’Ivoire (OR: 5.5, 95% CI: 2.1–14) had a moderately or highly increased risk of high-grade SIL, respectively. In the latter, the risk was statistically significant. Our findings emphasize the need for health initiatives targeted to prevent tobacco smoking or chewing among women especially in less industrialized countries.     

Anal squamous intraepithelial lesions are frequent among young HIV‐infected men who have sex with men followed up at the Spanish AIDS Research Network Cohort (CoRIS‐HPV)

The aim of our study was to determine the baseline prevalence of anal squamous intraepithelial lesions (SIL) and associated risk factors in HIV‐infected men who have sex with men (MSM) in a Spanish ongoing multicenter cohort. CoRIS‐HPV started in 2007, nested in the Spanish AIDS Research Network Cohort (CoRIS). Anal liquid cytology testing was performed. High‐risk human papillomavirus (HR‐HPV) infection was determined, and positive samples were genotyped. We analyzed all subjects up to April 2011. Multivariate logistic regression analyses were performed. A total of 551 subjects with baseline anal liquid cytologies were analyzed; 37.0% negative for intraepithelial lesion, 9.0% atypical squamous cells of uncertain significance (ASCUS), 41.0% low‐grade SIL, 4.0% high‐grade SIL and 9.0% inadequate. Prevalence of anal SIL (excluding ASCUS) in valid samples (n = 450) was 54.7% (95% confidence interval [CI] = 49.9–59.3). Globally HR‐HPV prevalence was 81.7% (95% CI = 78.0–85.2). Multiple infections (≥2 HR‐HPV genotypes) were documented in 77.7% (95% CI = 73.1–82.0). The only risk factor associated with anal SIL was the number of HR‐HPV types; MSM with five or more HR‐HPV genotypes had an odds ratio (OR) of anal SIL seven times greater (OR = 7.4; 95% CI = 2.8–19.6) than those with one HR‐HPV genotype. No associations were found for age, educational level, smoking, geographical origin, CD4 T‐cell count, antiretroviral treatment or number of sexual partners. The prevalence of anal SIL in young HIV‐positive MSM is high, and the main risk factor is multiple infections with HR‐HPV types.     

Multiple HPV infection in cervical cancer screened by HPVDNAChip

This study determined the distribution of high-risk HPV type infection in cervical cancer using newly developed oligonucleotide chips (HPVDNAChips). The study subjects included 80 cases of cervical neoplasia and 746 controls with a normal Pap smear. For HPV genotyping, the commercially available HPVDNAChips was used. The risk of cervical cancer was increased in women with a family history of cervical cancer (adjusted OR=2.3, 95% CI: 0.92-6.17) and in smokers (adjusted OR=3.2, 95% CI: 1.45-7.06). There was also a trend of increased risk with the number of full term pregnancies (P(for trend)<0.001). There were only 7.2% (54 of 746) infected high-risk HPV types in the control, whereas 54.5% (six of 11) and 76.5% (52 of 68) were infected in the CIN and cervical cancer, respectively. Multiple HPV infection was observed in 0.5% (three of 592) of the control group but in 9.1% (seven of 77) of cases. Multivariate analysis revealed that subjects infected with multiple HPV types had a 31.8-fold (95% CI: 7.50-134.75) higher risk of cervical cancer, while the single HPV type had a 19.9-fold increased risk (95% CI: 10.90-36.18) (P(for trend)<0.001). These results show that the detection and typing of HPV infection by HPVDNAChip can be a useful in clinical applications because it provides information on multiple infections and the types of HPV in addition to HPV infection status.     

Increased risk for cervical disease progression of French women infected with the human papillomavirus type 16 E6-350G variant.

To test the significance of human papillomavirus (HPV) type 16 and HPV16 E6 variants as risk factors for viral persistence and progression to high-grade lesion, we did a nested case-control study within a cohort study of >15,000 Caucasian French women. Three groups infected with high-risk HPV were compared: (a) women with cleared infection (controls, n = 201), (b) women with persistent infection (cases, n = 87), and (c) women who progressed into high-grade lesion (cases, n = 58). Women with persistent HPV infection and those that progressed into high-grade lesions were likelier to harbor HPV16 than other high-risk HPV types [odds ratio (OR), 2.4; 95% confidence interval (95% CI), 1.3-4.3 and OR, 4.2; 95% CI, 2.2-8.1, respectively]. Notably, especially elevated ORs of persistence (3.0; 95% CI, 1.4-6.7) and progression (6.2; 95% CI, 2.7-14.3) were found among women who harbored the HPV16 350G variant. Thus, HPV type and HPV16 variant seem to be risk factors for viral persistence and progression of infections into high-grade cervical lesions.