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Objectives: Establishing the prevalence of abnormal and inflammation cytology reports and its association with risks factors for uterine cervical neoplasms amongst females from the Cauca department in Colombia., Methodology: After signing a consent-form, females were interviewed using a questionnaire to collect socio-demographic and clinical data, including reproductive history, sexual activity, cytology history and smoking habits. Cytology was then taken for analysis and classification according to the 2001 Bethesda System. A total of 1,735 females were recruited for the study., Results: According to the cytology report, 1061 women had normal cytology (61 %), 36 abnormal cytology (2 %) and 638 reactive cellular changes associated with inflammation (37 %). The results indicated that having sexual intercourse at an early age, multiparity, using hormonal contraceptives and not having annual cytology screening were associated with abnormal cytology reports., Conclusions: These results provided valuable information for public health institutions for developing better screening programmes to prevent risks of uterine cervical neoplasms amongst females from our region and throughout Colombia.

Purpose of Investigation: The purpose of this study is to evaluate the significance of the c-Met / Hepatocyte Growth Factor Receptor (HGFR) expression in cervical intraepithelial neoplasia (CIN)., Materials and Methods: Twenty-one patients from two types of cervical intraepithelial neoplasias (LSIL and HSIL), diagnosed in our clinic were studied with c-Met immunohistochemistry. Of the 21 cases, five were diagnosed as LSIL and 16 as HSIL. Normal cervical mucosas from five patients were studied with c-Met as control cases., Results: Overexpression of c-Met was found in all five of LSIL specimens. C-Met overexpression was observed in 11 cases of HSIL. No c-Met overexpression was seen in any of the five control cases., Conclusion: These results revealed that c-Met oncogene overexpression is an important parameter in cervical early oncogenesis and may have a role in malignant transformation of cervical epithelial cells.

Purpose: To investigate the diet of patients with cervical cancer and precancerosis in the Wufeng area, a high- incidence region in China., Methods: In the case group, 104 patients diagnosed with cervical cancer or cervical intraepithelial neoplasias (CINII/III) were recruited from the Wufeng area. Nine hundred thirty-six healthy women were selected from the same area as the matched controls. A questionnaire, which included questions about general lifestyle conditions, smoking and alcohol status, source of drinking water, green tea intake, and diet in the past year, was presented to all participants., Results: Green tea intake (P=0.022, OR=0.551, 95% CI=0.330-0.919) and vegetable intake (P=0.035, OR=0.896, 95% CI=0.809-0.993) were identified as protective factors against cervical cancer or CINII/III. There was no indication of any associations of other lifestyle factors (smoking status, alcohol status, source of drinking water) or diet (intake of fruit, meat/egg/milk, soybean food, onion/garlic, staple food and pickled food) with cervical cancer., Conclusions: The results suggest that eating more fresh vegetables and drinking more green tea may help to reduce the risk of cervical cancer or CINII/III in people of the Wufeng area.

Objective: In 2004, we launched the question and answer (Q&A) section on a human papillomavirus (HPV) website (www.hpvkorea.org) that provides ample and regularly updated information about HPV. The purpose of this study is to collect data pertaining to questions posed on this website about HPV and its related diseases and analyze the type of questions and frequency before and after introduction of HPV vaccine in Korea. Using these results, we intend to determine the clinical and practical implications for doctors treating HPV and for HPV website providers., Method: Data were collected from March 2004 to July 2011. This study analyzed all the questions that were asked on the website during this period. The questions were categorized into 2 groups, according to whether they were asked publicly or privately. The 10 categories for classification were determined on the basis of the contents of the questions by 4 researchers with medical degrees (Ph.D.) related to HPV research. The frequency of the questions was separately determined for the public and private question formats. Also, we compared the type of questions and frequency before and after introduction of HPV vaccine in Korea and evaluated the changes in the 2 groups over the 2 periods studied., Results: Of the 3,062 subjects who visited the HPV website, 2,330 subjects asked public questions and 732 asked private questions. The most frequent question was "I have been infected with HPV, and I want to know about the treatment options for HPV infection and cervical dysplasia" (n = 1156, 37.8%), and the second most common question was "What are the transmission routes of HPV?" (n = 684, 22.3%). The third most common question was "How long does it take for HPV infection to spontaneously remit?" (n = 481, 15.7%).Of the 2,330 public questions, the most common question types pertained to the treatment of HPV and cervical dysplasia, HPV transmission, HPV remission, and risk of cervical cancer (in that order). Of the 732 private questions, the most frequent question types pertained to the HPV transmission, treatment of HPV and cervical dysplasia, genital warts, and HPV & pregnancy (in that order). The type and frequency of public and private questions showed statistical differences between the 2 groups (p < 0.001)., Conclusion: Our results show that when people consult an internet site about HPV, they actually want to seek about "treatment of HPV and cervical dysplasia", "HPV transmission", "HPV remission", "genital warts", and "risk of cervical cancer" (in this order). Also, our results showed that "genital warts" and "HPV & pregnancy" may have been considered embarrassing topics. Thus, these findings can be used to make informed recommendations for future clinical or internet-based communications with patients and the general public.

Stearoyl-CoA desaturase 1 (SCD1) is an essential lipogenic enzyme that has been shown to play an intrinsic role in the development of obesity and related conditions, such as insulin resistance. Through the generation of various mouse models of SCD1 deficiency, we have come to understand that SCD1 plays a role, directly or indirectly, in diverse metabolic processes, including lipogenesis, fatty acid oxidation, insulin signaling, thermogenesis, and inflammation. This review will address recent advances in our understanding of this key regulator of cellular metabolic processes, including the role of SCD1 in maintaining skin barrier integrity and the role of skin SCD1 in the metabolic phenotype elicited by global SCD1 deficiency., (© 2011 New York Academy of Sciences.)

The discovery that certain high-risk strains of human papillomavirus (HR-HPV) cause nearly 100% of invasive cervical cancer has spurred a revolution in cervical cancer prevention by promoting the development of viral vaccines. Although the efficacy of these vaccines has already been demonstrated, a complete understanding of viral latency and natural immunity is lacking, and solving these mysteries could help guide policies of cervical cancer screening and vaccine use. Here, we examine the epidemiological and biological understanding of the natural history of HPV infection, with an eye toward using these studies to guide the implementation of cervical cancer prevention strategies.

Background: The effect of combined oral contraceptives (COCs) and depot-medroxyprogesterone acetate (DMPA) on the area of cervical ectopy is not well understood., Study Design: From 1996 to 1999, we recruited women not using hormonal contraception from two family planning centers in Baltimore, MD. Upon study entry and 3, 6 and 12 months after the initial visit, participants were interviewed and received visual cervical examinations with photography. Ectopy was measured from digitized photographs and was analyzed both continuously and categorically (small [≤0.48 cm(2)] vs. large [>0.48 cm(2)])., Results: Of 1003 enrolled women, 802 returned for at least one follow-up visit. At 12 months, the numbers of women using COCs, DMPA or no hormonal method at least 50% of the time since the prior visit were 230, 76 and 229, respectively. After multivariable adjustment, COC use (vs. no hormonal use) was associated with large area of ectopy (odds ratio [OR]: 1.8, 95% confidence interval [CI]: 1.0-3.3). No significant relationship was observed between DMPA and large area of ectopy (OR: 0.5, 95% CI: 0.2-1.3). The incidence of large area of ectopy by contraceptive exposure (COC, DMPA or no hormonal method) was 17.4 (CI: 11.8-24.6), 10.9 (CI: 4.4-22.4) and 4.6 (CI: 2.2-8.4) per 100 woman-years, respectively., Conclusions: Use of COCs, but not DMPA, was associated with large area of cervical ectopy. Area of ectopy at baseline was the strongest predictor of area of ectopy at follow-up., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We present a case of a female kidney recipient who was infected with 3 types of high-risk human papilloma viruses. An infection in the lower genital tract led to the development of both neoplastic cervical lesions and vulvar cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Testing for high-risk human papillomavirus (HPV) in primary screening for cervical cancer is considered more sensitive, but less specific, in comparison with Pap-smear cytology. Women with persistent HPV infections have a higher risk of developing cervical intraepithelial neoplasia 2+ (CIN2+) lesions. This study was performed to evaluate the gain in specificity for detection of histologically confirmed CIN2+ lesions achieved by short-time repeat testing for high-risk HPV in women aged 30-65 years, with the primary sample for HPV analysis taken by self-sampling., Methods: A total of 8000 women in Uppsala County, aged 30-65 years, who had not attended organised screening for 6 years or longer, were offered self-sampling of vaginal fluid at home and the samples sent for HPV typing. Of these, 8% (669) were not possible to contact or had performed hysterectomy. Women positive for high-risk HPV in the self-sampling test were invited for a follow-up HPV test and a cervical biopsy on average 3 months after the initial HPV test., Results: In all, 39% (2850/7331) of invited women chose to perform self-sampling of vaginal fluid at home. High-risk HPV infection was found in 6.6% (188) of the women. In all, 89% of the women testing HPV positive performed a follow-up examination, on average 2.7 months, after the first test and 59% of these women were HPV positive in the follow-up test. The prevalence of CIN2+ lesions in women with an initial HPV-positive test was 23% (95% CI 18-30%) and in women with two consecutive HPV-positive tests was 41% (95% CI 31-51%). In women with two positive HPV tests, the prevalence of CIN2+ lesions varied from 49% in women at age 30-39 years to 24% in women at age 50-65 years. Short-time repeat HPV testing increased the specificity for detection of CIN2+ lesions from about 94.2% to 97.8%. The most prevalent HPV types were HPV16 (32%), followed by HPV18/45 (19%) and HPV 33/52/58 (19%)., Conclusion: The short-time persistence of high-risk HPV infection in this age group was about 60%. Repeat testing for high-risk HPV using self-sampling of vaginal fluid can be used to increase the specificity in the screening for cervical cancer in women aged 30-65 years.

Human papillomavirus (HPV) 52 and 58 are oncogenic HPV types prevalent in Asia. Our study aims to explore intratypic variants of HPV 52 and 58 in Taiwan. A total of 11,923 women were enrolled from seven townships in 1991-1992. HPV DNA in their cervical cells was detected and typed by EasyChip® HPV blot. Among 424 participants infected with HPV 52 and/or 58, nucleotide variations were determined in cervical cell samples of 406 participants by the polymerase chain reaction sequencing of the long control region, E6 and E7 genes. Nonprototype-like variants including lineages B and C were detected in 278 (99.3%) of 280 HPV 52 samples. The prototype and prototype-like group (lineage A) of HPV58 was found in 132 (98.5%) of 134 HPV 58 samples, with sublineage A1, A2 and A3 variant in 14.2, 27.6 and 56.7%, respectively. Among women infected with single HPV 52 type, the C variant (vs. B variant) was associated with an increased prevalence of cytologically diagnosed high-grade squamous intraepithelial lesion or worse lesions showing an age-adjusted odds ratio (95% confidence interval, CI) of 5.2 (1.0-27.6) and an increased prevalence of histologically confirmed high-grade cervical intraepithelial neoplasia or more severe lesions with an age-adjusted odds ratio (95% CI) of 7.6 (1.3-43.8). It was concluded that frequency distributions of HPV 52 and 58 variants in Taiwan were different from those in European and American populations. The association between C variant of HPV 52 and prevalence of cervical neoplasia needs further validation., (Copyright © 2010 UICC.)

High-risk human papillomaviruses (HPVs) are involved in the etiopathogenesis of cervical intraepithelial neoplasia (CIN) and cervical cancer. After taking HPV into account, smoking habit appears to be the most significant environmental risk factor, and the risk of this malignancy increases significantly with intensity and duration of smoking. Women with human immunodeficiency virus (HIV) infection experience a higher incidence of CIN and invasive cervical cancer. Among HIV+ women, the highly active antiretroviral therapy increases the regression rate of CIN, but the majority of these lesions do not regress to normal. As far as oral contraceptives (OCs), a systematic review of 28 studies found that, compared with never pill users, the relative risk (RR) of cervical cancer increased with increasing duration of OC use. The results were similar for squamous cell carcinoma and adenocarcinoma, and the RRs decreased after pill discontinuation. However, by weighing risks and benefits, the World Health Organization does not recommend any change in OC practice. There is no correlation between hormone replacement therapy and cervical cancer. Experimental data have shown that estradiol and progesterone can modulate the host immune response to HPV16. Prophylactic vaccination in conjunction with cervical screening is the best prevention strategy for cervical cancer.

Purpose: The percent of young patients treated for cervical intraepithelial neoplasias (CIN) has been increasing, thus it is very important to define patients in high risk for relapse. The aim of this study was to establish any possible association of persistent human papillomavirus (HPV) infection, age, smoking, parity, use of oral contraceptives, and Chlamydia infection, with relapse of CIN., Methods: Between March 2006 and March 2009 a prospective clinical study was performed at the Clinic of Obstetrics and Gynecology in Nis, with the study group comprising the first 35 patients with disease relapse after conization and the control group consisting of 30 patients with more than one year after treatment without relapse. HPV typization was done at the Laboratory for Molecular Biology and Cytogenetics of the Clinical Centre Nis using polymerase chain reaction (PCR)., Results: A statistically significant higher percentage of recurrences with lower pathologic stage (CIN I) was found in younger women (below 29 years) (p<0.01). Women in the control group were more commonly non smokers (56.66 vs. 40%) but without statistical significance (p>0.05). The distribution of smoked cigarettes in the study and control subjects showed no statistically significant difference (p>0.05). Patients with recurrences were more commonly HPV-positive compared to controls (68.57 vs. 6.66%; p <0.05). In the study group, HPV-positive smokers recurred with more advanced grades (CIN III and microinvasive carcinoma/MIC; p<0.01). In non smokers, the severity of recurrence was not statistically correlated with HPV positivity., Conclusion: Persistent HPV infection, smoking associated with HPV infection and more advanced age were demonstrated to be of statistical significance for CIN recurrence. Parity, use of oral contraceptives, Chlamydia infection, and smoking as independent etiologic factors were not significantly associated with CIN relapse.

Background: Cervical cancer is the second biggest cause of death among human female cancers. Human papillomavirus (HPV) is the main factor in this cancer, especially HPV types 16 and 18, which constitute the high-risk group. There are 2 physical states of HPV in host cells: integrated and episomal forms. Our previous study explored the very high degree of cyclin A1 (CCNA1) promoter methylation in invasive cervical cancer in which all cases were infected by HPV., Objective: From previous evidence, it seemed that HPV might affect CCNA1 promoter methylation. Therefore, both the quantity and physical state of HPV were investigated in this study for their effects on CCNA1 promoter methylation., Materials and Methods: To determine the correlation of HPV quantity and CCNA1 methylation, the proportion of HPV L1/HAT (histone acetyltransferase, which is a human housekeeping gene) and the percentage intensity of CCNA1 promoter methylation were observed. CCNA1 promoter methylation was detected by methylation-specific primer polymerase chain reaction. To investigate the physical state, the HPV E2 region was amplified. The effect of the physical state on CCNA1 methylation was observed., Results: No correlation was found between the quantity of HPV and CCNA1 promoter methylation. Interestingly, the physical state of HPV had the potential to affect methylation of this gene. The integrated form of HPV had a significantly higher impact on CCNA1 methylation than HPV in episomal form (P=0.001; 95% confidence interval, 11.96-38.44)., Conclusion: We suggest that the integrated form of HPV might lead to CCNA1 promoter methylation in cervical cancer by some mechanisms.

Objective: This study aimed to compare cervical cytologic and histologic findings between women using depot-medroxyprogesterone acetate (DMPA) and oral contraceptives (OCs) referred for colposcopy and to determine whether there were differences in the occurrence of false-positive cytologic finding between the 2 contraceptive groups., Materials and Methods: Retrospective cohort of 1,569 premenopausal women using either DMPA or OC who were evaluated for abnormal cervical cytologic findings. Cytologic and histologic data were collected in conjunction with routine gynecologic examinations or follow-up colposcopic evaluations. χ2 tests were used to determine differences in cervical cytologic and histologic findings and the proportion of false-positive results across contraceptive groups. Nominal logistic regression was used to evaluate the association between contraceptive use, cervical, and histologic abnormalities while controlling or age and smoking status., Results: The mean age of all participants was 23.5 years, with no significant difference between OC (n = 1194) and DMPA (n = 375) users. Although there were no differences in the proportion of false-positive cytologic results (21.8% overall), DMPA users were more likely to smoke (p < .001), have atypical glandular cell (AGC) on referral cytology (p < .001), and have histologic confirmation of cervical intraepithelial neoplasia 2, 3 (p = .004). Users of DMPA remained more likely to have AGC cytology after considering smoking status; however, cervical intraepithelial neoplasia 2, 3 was found to be associated with smoking status and not use of DMPA., Conclusions: We found no difference in the proportion of false-positive cytologic results between DMPA and OC users referred for evaluation of abnormal cytology. Users of DMPA were more likely to have AGC, which necessitates a more comprehensive evaluation.

Objective: To investigate the potential value of tree classifiers for the triage of high-grade squamous intraepithelial lesions., Study Design: The dataset comprised 808 histologically confirmed cases having a complete range of the cytologic sample assessments--liquid-based cytology, reflex human papillomavirus (HPV) DNA test, E6/E7 HPV mRNA test, and p16 immunocytochemical examinations. Data include 488 histologically negative (cervical intraepithelial neoplasia [CIN] 1 and below) or clinically negative cases and 320 with histologic diagnosis of CIN 2 or worse. Cytologic diagnosis was made according to the criteria of the Bethesda System. Cases were classified in two groups according to histology: those with CIN 2 or worse and those with CIN 1 and below. Fifty percent were randomly selected as a training set and the remaining were as a test set., Results: Application of tree classifier on the test set gave correct classification of 66.9% for CIN 2 and above cases and 97.3% for CIN 1 and below, producing overall accuracy of 91.5%, outperforming cytologic diagnosis alone., Conclusion: Application of tree classifiers, based on standard cytologic diagnosis and expression of studied biomarkers, produces improved classification results for cervical precancerous lesions and cancer diagnosis and

The objective of this study was to estimate the prevalence of cytological abnormalities of the anal mucosa in women with positive cervical cytology, but without macroscopic anal lesion. Ultimately we postulated if the anal mucosa may be a reservoir of HPV, which would allow the reinfection of cervix. Forty-nine patients with abnormal cervical cytology were selected for this work. In a period not exceeding one week of collecting cervix cytology, two swab specimens of the anal canal were also collected. Women diagnosed with cervical HSIL by Pap smear were referred for colposcopy with biopsy of the lesions, to confirm the cytologic diagnosis and ablation of the lesion. We demonstrated a high prevalence of anal squamous intraepithelial lesions in patients with cervical squamous intraepithelial lesions (29 of the total of 49 patients = 59.2%). Of the 20 cases of cervical LSIL, 11 (55%) had abnormal anal cytology. Of the 26 cases with cervical HSIL, 16 (61.5%) had abnormal anal cytology. So, there was a discrete higher prevalence of abnormal anal cytology in cases of high-grade cervical squamous lesions (cervical HSIL). These results help to support the hypothesis that the anal mucosa is a reservoir of HPV, which can be a source of re-infection for the cervix. However, there was no significant association between the practice of anal sex and the prevalence of anal cytological abnormalities. These facts are epidemiologically important for future programs for population eradication of cervical lesions related to HPV. Diagn. Cytopathol. 2011;39:323-327. © 2010 Wiley-Liss, Inc., (Copyright © 2010 Wiley-Liss, Inc.)

The objective of this study was to evaluate the incidence of genital human papilloma virus (HPV) infection and cervical intra-epithelial lesions in transplanted patients. Cervical Papanicolaou (Pap) smear/HPV test and colposcopic examinations were performed in 58 patients who were candidates for renal transplant surgery; these tests were repeated one year later. Their age range was 26-53 years (mean, 37.2 years). Hypertension was the most common cause of renal insufficiency (34.4%), while in 41.4% of the patients, the causative pathology was unknown. In 24.1% of the patients, there was no history of dialysis, i.e. they had pre-emptive transplantation. The mean duration of marriage (years since first intercourse) was 16.2 years (range, 1-35). Coitus interruptus was the most common contraceptive method used (37.9%), followed by tubal ligation and condom (10.3% and 6.9%, respectively). All patients had negative Pap tests and normal gynecologic exam before undergoing transplantation. The Pap test remained normal after transplant surgery, although the HPV test became positive in four patients (6.9%). There were five cases of white epithelium on colposcopy, but biopsy showed normal metaplasia. Two cases of extensive anogenital warts were treated by CO 2 laser, and one patient had recurrent warts, which responded well to second laser surgery. None of the study patients had squamous intra-epithelial lesions (SIL) or vulvar intra-epithelial neoplasia. Our study suggests that screening with HPV and Pap test should be performed before transplant surgery and should be repeated at regular intervals in order to avoid irreversible situations such as high-grade SILs, which are difficult to treat. Avoiding high-risk sexual relations in this group of patients is highly recommended.

Background: To prove a causal link between an epigenetic change and an environmental or behavioural risk factor for a given disease, it is first necessary to show that the onset of exposure precedes the first detection of that epigenetic change in subjects who are still free of disease., Methods: Towards this end, a cohort of women aged 15-19 years, recruited soon after they first had sexual intercourse, were used to provide sequential observations on the relationship between cigarette smoking and the detection in cervical cytological samples of methylated forms of CDKN2A (p16) using nested methylation-specific polymerase chain reaction., Results: Among women who remained cytologically normal and who tested negative for human papillomavirus DNA in cervical smears during follow-up, those who first started to smoke during follow-up had an increased risk of acquiring CDKN2A methylation compared with never-smokers (odds ratio=3.67; 95% confidence interval 1.09-12.33; P=0.04)., Conclusion: Smoking initiation is associated with the appearance of methylated forms of CDKN2A.

Objective: Due to the low sensitivity of Pap smear, premalignant lesions of the cervix can be missed in women with inflammatory Pap smears. However, it is not practically possible to subject all women with inflammatory Pap smear to colposcopy. This study was carried out with the aim to evaluate whether women with persistent inflammation on Pap smear need further evaluation with colposcopy., Materials and Methods: Four hundred and twenty women were screened at a tertiary level hospital with Pap smear. Women with inflammation on Pap smear were given treatment as per WHO guidelines and Pap smear was repeated at an interval of 6-12 weeks. Women with persistent inflammation on Pap smear were then subjected to colposcopy and directed biopsy if required., Results: Of the 420 women screened, 102 (24.3%) women had a Pap smear showing inflammation. Thirty six women (8.6%) had persistent inflammatory Pap smear. Thirty women were subjected to colposcopy and 16 (53.3%) had abnormal findings on colposcopy. Five out of these 30 women (16.67%) had Cervical intraepithelial neoplasia (CIN) on biopsy., Conclusions: Nearly 16.67% women with persistent inflammation on Pap smear had cervical intraepithelial neoplasia. Hence, a large number of women with CIN would be missed if persistent inflammation on Pap smear is not evaluated further.

Objectives: The objective of the study was to determine the prevalence and clinical significance of atypical glandular cells (AGC) or atypical glandular cells of undetermined significance (AGUS) diagnosed in pregnant and postpartum women., Study Design: Smears having a diagnosis of AGC or AGUS, taken from pregnant and postpartum (within six weeks after delivery) women between 1995 and 2008 were reviewed and subclassified according to the Bethesda 2001 classification. Case records were then reviewed and a second cytology review was performed after disclosure of the follow-up data., Results: Among 91,133 smears taken from pregnant and postpartum women, 70 had AGC or AGUS (0.07%) diagnosed. Follow-up data were available in 40 cases, with mean duration of follow-up being 43 months. Among the 40 patients with follow-up data, nineteen had smears with coexisting squamous abnormalities. Thirty patients had positive pathology, including 18 (45%) cervical intraepithelial neoplasia III (CIN III), four (10%) cervical adenocarcinoma-in situ, three (7.5%) squamous cell carcinoma of cervix, four (10%) condylomas and one (2.5%) hydatidiform mole. On review, 24 out of 32 smears with AGC 'not otherwise specified' ('NOS') had significant pathology., Conclusions: AGC found on cervical smears during pregnancy and the postpartum period is uncommon. The chance of having significant cervical pathology, however, is high and colposcopy should be performed., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Smoking has been positively and fruit and vegetable intake has been negatively associated with cervical cancer, the second most common cancer among women worldwide. However, a lower consumption of fruits and reduced serum carotenoids have been observed among smokers. It is not known whether the smoking effect on the risk of cervical neoplasia is modified by a low intake of fruits and vegetables. The present study examined the combined effects of tobacco smoking and diet using a validated FFQ and serum carotenoid and tocopherol levels on cervical intraepithelial neoplasia grade 3 (CIN3) risk in a hospital-based case-control study conducted in São Paulo, Brazil, between 2003 and 2005. The sample comprised 231 incident, histologically confirmed cases of CIN3 and 453 controls. A low intake ( ≤ 39 g) of dark-green and deep-yellow vegetables and fruits without tobacco smoking had a lesser effect on CIN3 (OR 1·14; 95 % CI 0·49, 2·65) than among smokers with higher intake ( ≥ 40 g; OR 1·83; 95 % CI 0·73, 4·62) after adjusting for confounders. The OR for the joint exposure of tobacco smoking and low intake of vegetables and fruits was greater (3·86; 95 % CI 1·74, 8·57; P for trend < 0·001) compared with non-smokers with higher intake after adjusting for confounding variables and human papillomavirus status. Similar results were observed for total fruit, serum total carotene (including β-, α- and γ-carotene) and tocopherols. These findings suggest that the effect of nutritional factors on CIN3 is modified by smoking.

The present study aimed to evaluate a novel fluorescence in situ hybridization (FISH) assay for detecting the high-risk human papillomavirus (HR-HPV) DNA and signal pattern in cervical cytology specimens and for identifying cervical intraepithelial neoplasia (CIN) lesions. One hundred and ninety-six liquid-based cytology specimens with CIN were recruited. The signal pattern (punctate, mixed punctate and diffuse, and diffuse) detected by FISH was compared with E6 mRNA and correlated with histological classification. FISH and E6-type specific polymerase chain reaction (PCR) had fair to good agreement for detecting HPV DNA across all grades of CIN (kappa coefficient, 0.37-0.73). Among 44 samples of negative FISH and positive E6 type-specific PCR in HPV 16, 18, 31, 33, 52 and 58, 82% (36/44) of E6 mRNA were not detected, in contrast to 41% (48/118) of positive FISH and positive E6 type-specific PCR (p <0.0001). Among HR-HPV DNA positive cases tested by the FISH assay, the specificity of predicting CIN3 using the punctuate pattern is higher than that using E6 mRNA (96.3% vs. 44.8%). The punctate pattern was 0% in patients with

Objective: We sought to evaluate the association between passive cigarette smoke exposure and cervical cytological abnormalities in a predominantly Hispanic sample., Study Design: Data were collected as part of a larger, ongoing randomized clinical trial. Inclusion criteria were met by 4403 Hispanic (73%) and non-Hispanic (27%) women between 18-55 years of age (mean = 30.14 ± 8.7). Analysis of variance and multivariate logistic regression determined the association between passive smoke exposure and Pap abnormality., Results: Passive smoke exposure was positively associated with having an abnormal Pap smear (odds ratio, 1.70; 95% confidence interval, 1.14-2.52) as was current active smoking (odds ratio 1.45; 95% confidence interval, 1.03-2.04). Neither effect was modified by ethnicity. Increasing hours per week of passive smoke exposure was associated with low-grade squamous intraepithelial lesion (P < .05)., Conclusion: Passive smoke exposure is an important independent risk factor for cytological abnormalities in Hispanic and non-Hispanic women. This study adds to the growing body of evidence of the dangers of passive smoke exposure., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Vaginal douching is a common practice worldwide. Its effect on the natural history of the early lesion of human papillomavirus (HPV) infection, low-grade squamous intraepithelial lesion (LSIL), is unknown., Methods: In a prospective nation-wide cohort (n=1332), epidemiological variables including habit of vaginal douching after intercourse and outcomes of LSIL were studied. Colposcopy-confirmed LSIL women (n=295) were followed every 3 months. Parameters of HPV infection, sexual behavior, personal hygiene and environmental exposures were compared with the follow-up outcomes., Results: There was a 15% chance of HSIL co-existing with the LSIL cytology result. Eight percent of colposcopy-confirmed LSIL were found with HSIL in 1 year. With a follow-up of up to 36 months, 83% LSIL regressed, 11% progressed and 6% persisted. The mean time (95% CIs) to regression and progression were 5.2 (4.7-5.8) and 8.0 (5.8-10.3) months, respectively. Risk factors of the non-regression of LSIL included HPV prevalence on enrollment, habit of vaginal douching after intercourse with a hygiene product and non-regular Pap screening, with odd ratio of 4.4 (1.9-10.3), 3.14 (1.04-9.49) and 2.12 (1.24-3.62), respectively. HPV prevalence and vaginal douching also conferred a slower regression of LSIL (8.0 vs. 4.1 months, P<.001 and 8.0 vs. 5.6 months, P=0.02, respectively)., Conclusion: The study disclosed a transient but warning nature of cytological LSIL. Practicing of vaginal douching after intercourse, especially with hygiene products, is associated with non-regression of LSIL., (Copyright © 2010. Published by Elsevier Inc.)

Background: Infection with multiple types of human papillomavirus (HPV) is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1,810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively., Principal Findings: The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%), while this risk decreased in women who had given birth more than 4 times (-31.1%), or were of mestizo (-24.6%) or black (-40.9%) ethnicity., Conclusions: According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2-4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies.

Objective: To determine the incremental costs and effects of different HPV testing strategies, when compared to Papanicolau cytology (Pap), for cervical cancer screening in Mexico., Methods: A cost-effectiveness analysis (CEA) examined the specific costs and health outcomes associated with (1) no screening; (2) only the Pap test; (3) only self-administered HPV; (4) only clinician administered HPV; and (5) clinician administered HPV plus the Pap test. The costs of self- and clinician-HPV testing, as well as with the Pap test, were identified and quantified. Costs were reported in 2008 US dollars. The health outcome associated with these screening strategies was defined as the number of high-grade cervical intraepithelial neoplasia or cervical cancer cases detected. This CEA was performed using the perspective of the Mexican Institute of Social Security (IMSS) in Morelos, Mexico., Results: Screening women between the ages of 30-80 for cervical cancer using clinical-HPV testing or the combination of clinical-HPV testing, and the Pap is always more cost-effective than using the Pap test alone., Conclusions: This CEA indicates that HPV testing could be a cost-effective screening alternative for a large health delivery organization such as IMSS. These results may help policy-makers implement HPV testing as part of the IMSS cervical cancer screening program.

Recent data indicate that persistent HR-HPV infections represent a significantly increased risk of developing incident high-grade CIN and cervical cancer. Accordingly, 6-month (6M+) or 12-month (12M+) type-specific persistence of HR-HPV have been proposed as powerful surrogates of progressive disease. Because of substantial practical impact in future HPV vaccine trials using non-HPV 16/18 vaccines, studies on HR-HPV persistence as a surrogate endpoint of progressive CIN have been subject to a comprehensive meta-analyses recently. The present communication was solicited to bring this important and timely topic to the awareness of the readers, in a format consisting of a review of the recent literature, supplemented with the author's own experience from different studies. Based on a large number of relevant studies, there remains little doubt that persistence of HR-HPV for 6+ or 12+ months is associated with a significantly increased risk of developing incident high-grade CIN. However, some data also disclosed several important issues that need to be carefully considered and/or adequately resolved before adopting 6M+ or 12M+ HR-HPV persistence as a surrogate of progressive disease. These include i) definitions of HPV persistence, ii) HPV detection techniques and iii) testing intervals and iv) length of follow-up, as well as v) diagnosis of the surrogate endpoints, and vi) other study characteristics, including vii) the type of reference category used in calculating the risk estimates. All these issues are critically discussed in the present communication. Of major impact seems to be the reference category used to calculate these risk estimates, as evident from the NIS-LAMS cohort. Taken together, it is suggested that in all future studies using the 6M+ or 12M+ HR-HPV persistence as a surrogate endpoint of progressive disease, a "gold standard" should be used in calculating the risk estimates. In addition to deciding, 1) whether to use 6M+ or 12M+ persistence criteria, and 2) cytological, histological or combined surrogate endpoints (SIL, CIN1, CIN2, CIN/SIL), one should 3) use exclusively the HPV negative reference group in calculating the risk estimates for viral persistence endpoints. This is supported by the data from the recent meta-analysis as well as from the author's combined NIS-LAMS cohort, both implicating that the most consistent association to progressive disease is obtained when women with persistent HR-HPV are compared with HPV-negative women. It is the conviction of this author that the two other reference categories (HPV transient and HPV mixed outcome) are far too heterogeneous and subject to potential misclassifications to give consistent and reproducible risk estimates for HR-HPV persistence as a surrogate endpoint of progressive CIN.

With heterosexual transmission becoming the primary mode of transmission, more women are being infected with human immunodeficiency virus (HIV). Accrued data from around the world indicate that these HIV-infected women exhibit higher rates of persistent HPV infection with multiple oncogenic viruses, more abnormal Pap tests, more prevalent cervical intraepithelial neoplasia (CIN) lesions, and aggressive invasive cervical cancer compared with their HIV-negative counterparts. In countries where HAART was introduced more than a decade ago, HPV-related disease is increasing among ageing HIV-positive women. The high rate of cervical disease seen in HIV-positive women has prompted recommendations for more aggressive surveillance. The best strategy to screen HIV-infected women, particularly in resource-poor nations, remains challenging. This article reviews the collective literature regarding HIV and squamous lesions of the cervix and highlights these key issues., (Copyright © 2010 Wiley-Liss, Inc.)

Background: The clinical relevance of human papillomavirus type 16 (HPV16) DNA methylation has not been well documented, although its role in modulation of viral transcription is recognized., Methods: Study subjects were 211 women attending Planned Parenthood clinics in Western Washington for routine Papanicolaou screening who were HPV16 positive at the screening and/or subsequent colposcopy visit. Methylation of 11 CpG dinucleotides in the 3' end of the long control region of the HPV16 genome was examined by sequencing the cloned polymerase chain reaction products. The association between risk of CIN2/3 and degree of CpG methylation was estimated using a logistic regression model., Results: CIN2/3 was histologically confirmed in 94 (44.5%) of 211 HPV16 positive women. The likelihood of being diagnosed as CIN2/3 increased significantly with decreasing numbers of methylated CpGs (meCpGs) in the 3' end of the long control region (P(for trend) = 0.003). After adjusting for HPV16 variants, number of HPV16-positive visits, current smoking status and lifetime number of male sex partners, the odds ratio for the association of CIN2/3 with ≥4 meCpGs was 0.31 (95% confidence interval, 0.12-0.79). The proportion of ≥4 meCpGs decreased appreciably as the severity of the cervical lesion increased (P(for trend) = 0.001). The inverse association remained similar when CIN3 was used as the clinical endpoint. Although not statistically significant, the ≥4 meCpGs-related risk reduction was more substantial among current, as compared to noncurrent, smokers., Conclusion: Results suggest that degree of the viral genome methylation is related to the outcome of an HPV16 cervical infection.

Aims: To evaluate the role of hormonal contraceptives as a risk factor of high-risk human papillomavirus (HR-HPV), cervical intraepithelial lesions (CIN) and cervical cancer in our multi-center population-based LAMS (Latin American Screening) study., Methods: A cohort study with >12,000 women from Brazil and Argentina using logistic regression to analyze the covariates of hormonal contraception (HOC - oral, injections, patches, implants, vaginal ring and progesterone intrauterine system) use followed by multivariate modeling for predictors of HR-HPV and CIN2+., Results: HR-HPV infection was a consistent risk factor of high-grade CIN in all three groups of women. The length of HOC use was not significantly related to high-grade squamous intraepithelial lesions (HSIL)+ Pap (p = 0.069), LSIL+ Pap (p = 0.781) or ASCUS+ (p = 0.231). The same was true with the length of HOC use and histology CIN3+ (p = 0.115) and CIN2+ (p = 0.515). Frequently, HOC users have previously shown more HPV-related lesions, as well as lower HPV prevalence if they were current smokers. But HOC use and time of usage were not independent risk factors of either HR-HPV infection or high-grade CIN using multiple logistic regressions., Conclusions: No evidence was found for an association between the use of HOC with an increased risk for HR-HPV infection or high-grade CIN in this cohort., (Copyright © 2010 S. Karger AG, Basel.)

Objective: Age-adjusted evaluations have explored the possible utility of human papillomavirus (HPV) test results in women with low-grade squamous intra-epithelial lesion (LSIL) Paps. We document LSIL correlation data with HPV test results and histopathologic follow-up from a large academic women's hospital practice., Study Design: LSIL Pap tests with intermediate-/high-risk HPV DNA testing between July 1, 2005 and April 30, 2008 were studied along with follow-up histopathologic diagnoses. Patients were divided into age groups, and tissue diagnoses were correlated with HPV test results., Results: 1,083 (80.2%) of a total of 1,351 LSIL Pap samples tested HPV positive. HPV prevalence declined in older age groups. 719 women with LSIL Pap and HPV test results had at least 1 follow-up cervical biopsy result. 89 of 612 patients with HPV-positive LSIL (14.5%) had a follow-up histopathological diagnosis of cervical intra-epithelial neoplasia (CIN) 2/3. Only 4 of 107 patients with HPV-negative LSIL (3.7%) had CIN 2/3., Conclusions: In the largest study to date to document histopathological follow-up of older women with LSIL and HPV test results, no histopathological CIN 2/3 diagnoses were identified in women 50 years and older with HPV-negative LSIL. HPV test results stratified women with LSIL cytology findings into lower- and higher-risk groups for follow-up histopathologic CIN 2/3 outcomes., (Copyright © 2010 S. Karger AG, Basel.)

Introduction: Human papillomavirus (HPV) prevalence and type distribution were estimated among 90 female sex workers (FSWs) aged 18 to 58 years in Antananarivo, Madagascar., Methods: A total of 90 FSWs aged 18 to 58 years in Antananarivo, Madagascar, were included in this study. Information on sexual and behavioral characteristics was obtained via a questionnaire. Exfoliated cervical cell specimens were collected for conventional cytologic examination and HPV DNA testing by polymerase chain reaction. The prevalence rates of HPV DNA and their corresponding 95% confidence intervals were stratified into the following 3 age groups: younger than 25, 25 to 34, and 35 years or older. To assess the association between HPV DNA positivity and sociodemographic and sexual behavioral factors, age-adjusted odds ratios and 95% confidence intervals were calculated using unconditional logistic regression., Results: The HPV prevalence in exfoliated cervical cell specimens was 36.7%. The most common HPV types found were HPV-52 (11.1%), HPV-31 and -39 (each at 5.6%), and HPV-16 and -83 (each at 3.3%). The prevalence of low-grade squamous intraepithelial lesions was 3.3%, and that of atypical squamous cells of undetermined significance was 18.9%. No high-grade lesion was found. Although associations were imprecise, the HPV prevalence was higher among women who reported younger age at the first intercourse, contraceptive use, a history of cervical lesions, and no history of condom use., Discussion: The prevalence rates of HPV and cervical lesions among FSWs in Madagascar appear higher than among FSW populations from other African countries with a relatively higher population-based prevalence of human immunodeficiency virus infection.

Introduction: Cervical cancer is the second most common cancer in women worldwide. In countries like Mexico, cervical cancer early detection programs have had a minimal impact on the incidence and death rates from cervical cancer. Self-sampling for the presence of high-risk human papillomavirus is potentially a more effective screening tool to reach women who have limited access to community healthcare resources. The objective of this phase 2 trial was to establish if the fourth generation Preventive Oncology International/National Institutes of Health self-sampler device is well accepted by women of all socioeconomic levels in Michoacán, Mexico., Methods: This is a prospective phase 2 trial. The patients used the self-sampler, and then the acceptability questionnaire (14 multiple choice questions) was completed with the assistance of nursing staff., Results: Two thousand five hundred seventeen patients completed the questionnaire. The mean age of our patient population was 39 years. Eighty-six percent of patients reported being comfortable when using the self-test, and 76% preferred to do the test at the clinic. Ninety-one percent of patients said that if their only choice was to perform the test at home they would perform it rather than not perform the test. The major barriers for the use of self-sampler identified by the women in the study were fear (75%), woman might not perform the test because she does not feel ill (70%), women felt that husbands may stand in women's way of performing the test (66%), and lack of time (61%). Results differed by location but not by history of Papanicolaou test., Conclusions: Most patients reported being comfortable when using the Preventive Oncology International/National Institutes of Health fourth generation self-test. Most influential barriers identified by the acceptability questionnaire were fear, lack of signs or symptoms of illness, husbands' influence, cost, lack of time, being unable to read, and lack of trust in the medical community.

Introduction: When apoptosis is disrupted, the transformed cells can survive, proliferate, and evolve into a malignancy. The strictly conserved caspase genes and the reliable experimental data clearly show that some caspases play a crucial role in apoptosis even if some of them have no apoptotic activity and others exhibit both apoptotic and nonapoptotic properties. Although caspase-2 belongs to initiator caspases, its normal role remains unclear. Experimental studies have shown that it is primarily necessary for the execution of apoptosis in mutagenic cells. Human caspase-5 is classified as an inflammatory caspase, although its substrate has not been identified yet. In this research, the activities of caspase-2 and caspase-5 have been estimated during the progression of human cervical malignancy., Methods: The experimental material includes human cervical tissue samples (normal and pathological) and blood serum samples of the corresponding tissue donors, where enzyme activities have been measured colorimetrically., Results: Both caspases' activities showed the highest increase, statistically significant (P < 0.01, by t test) compared with the controls, in the low-grade squamous intraepithelial lesion tissues. Caspase-2 of all pathological tissues was proved more active than the controls. Serum caspases' activities were significantly lower than those of the tissues. Serum caspase-2's activity in patients with low-grade squamous intraepithelial lesion stage showed no statistically significant increase compared with the controls. Serum caspase-5's activity of all patients with malignancy stages was presented elevated, whereas that of the serum of patients with cervical cancer had the highest activity (P < 0.01, by t test)., Conclusions: The changes of caspase-2 and caspase-5 activities could be indicative of their involvement in the cervical malignancy mechanisms.

Introduction: Testing for high-risk types of human papillomavirus (HPV) has been consistently more sensitive than cervical cytology for high-grade precancers and cancers of the cervix (cervical intraepithelial neoplasia grade 2 or higher) but less specific. New assays are being developed to improve on the overall accuracy of molecular testing. The Gen-Probe APTIMA HPV assay (AHPV) is a multiplex assay that qualitatively detects 14 HPV types in a single tube. Because the AHPV targets HPV-E6/E7 messenger RNA transcripts, it should theoretically have a greater specificity than HPV assays that detect HPV DNA. The objective of this study was to compare the sensitivity and the specificity of the Gen-Probe AHPV with those of the Qiagen Hybrid Capture 2 assay (HC2) and liquid-based cytologic examination for cervical cancer screening., Methods: A total of 2098 unscreened or poorly screened women 25 to 59 years of age were recruited in the city of Shenzhen, China. Two cervical specimens were collected: 1 in SurePath liquid for cytologic examination and 1 in PreservCyt for HPV testing by HC2 and the AHPV. The testing was performed by blinded technicians according to the manufacturer's instructions. Women who had atypical squamous cells of undetermined significance or worse cytologic diagnosis and/or were HPV positive by either assay were asked to return for colposcopy and biopsy., Results: Overall, 2095 women had complete data. Overall, 16.5% of the women were positive on HC2, 10.1% were positive on the AHPV, 5.45% had atypical squamous cells of undetermined significance or greater on cytologic examination, and 1.4% had histologically confirmed cervical disease: cervical intraepithelial neoplasia grade 2 or higher. The sensitivity values of liquid-based cytologic examination, HC2, and the AHPV were 66.7%, 88.9%, and 100%, respectively. The specificity values were 95.5%, 84.5%, and 91.2%, respectively. The AHPV was significantly more accurate by receiver operating characteristic curve comparison (P = 0.005)., Conclusions: The low false-positive rate (high specificity) and the high sensitivity of the AHPV makes this assay suitable for use as a primary assay for detecting cervical disease in a screening setting.

Introduction: Human papillomavirus (HPV) type 16 is the major etiological agents of cervical cancer. Recently, the studies have demonstrated that HPV intratypic variations could affect oncogenic potential to cervical cancer development. The objectives of this study were to identify HPV-16 E6 and E7 variants prevalent in Chinese women and to assess the risk of them for invasive cervical carcinoma and cervical intraepithelial neoplasia (CIN)., Methods: DNA samples were genotyped by flow-through hybridization (HybriMax) and amplified by using primers specific for E6 and E7. Products were directly sequenced and analyzed using BLAST on PubMed., Results: A total of 170 cervical samples (33 cases of normal control, 11 of CIN 1, 72 of CIN 2-3, and 54 of invasive cervical carcinoma) were HPV-16-positive and were analyzed for E6 and E7 sequence variation. The results showed that HPV-16 Asian lineage was the most frequently detected (77%) and that the Asian variant presented a significantly higher disease risk for cervical cancer and CIN. In addition, 3 novel variants at E6 (Q20P, H118Q, and Q123K) and 2 at E7 (D75N and T86P) were found. The substitution G368T at E6 leading to a premature stop codon occurred in an isolate of normal control sample., Conclusions: This study reported the distribution of HPV-16 E6 and E7 gene variations in women from southeastern China, which are different from that showed in previous studies and may be important when developing an effective vaccine for this area.

Introduction: Testing for high-risk (HR) human papillomavirus (HPV) infection, a prerequisite of invasive cervical cancer (ICC), has been proposed for primary cervical cancer screening. However, the low specificity limits its clinical significance. Although the risk factors for ICC have been extensively studied, whether the existence of risk factors is associated with the specificity of HR-HPV testing in primary screening is unknown. Our study aimed to evaluate the effects of triage by risk factors on HR-HPV testing for detecting cervical intraepithelial neoplasia grade 2 or worse in cervical cancer screening., Methods: A hospital-based case-control study was conducted to explore the risk factors of ICC, and the predictors obtained were selected as potential triage factors. In population-based screening, potential triage factors associated with cervical intraepithelial neoplasia grade 2 or worse were selected as triage factors, and the performance of HR-HPV testing with triage factors was evaluated., Results: Lifetime number of sexual partners was selected as a triage factor. With the triage factor, the specificity of HR-HPV testing increased significantly, both in the strata of normal (P = 0.000) and abnormal cytological examination findings (P = 0.030). While stratified by age, no significant differences were observed for women younger than 30 years, but the specificity and the accuracy of the HR-HPV testing increased significantly (P = 0.000 and P = 0.000, respectively) among women aged 30 years or older., Conclusions: Triage by risk factors is a potentially simple and feasible method to increase the specificity of HR-HPV testing for cervical cancer screening.

Objective: to investigate high risk factors associated with cervical intraepithelial neoplasia (CIN) in married women aged 25 to 54 years in Beijing., Methods: from Mar. 2007 to Sep. 2008, 6339 married women at age of 25 to 54 years were selected randomly by cross sectional survey in a total of 137 communities of 12 districts or counties in Beijing. The interview was carried out with unified questionnaires, gynecological examination. The cervical smear cytology and high-risk human papillomavirus (HR-HPV) infection of cervical secretion were detected. Women with abnormal cervical cytology underwent colposcopy and cervical biopsy. Odd ratio (OR) and 95% confidence interval (CI) of related high risk factors with CIN were studied by logistic regression analysis., Results: among 6339 women, the prevalence rate of CIN including 4 squamous cell carcinoma (SCC) was 5.90% (374/6339). By multinomial regression analysis, HR-HPV infection (95%CI: 9.953 - 15.811), History of trichomonas vaginitis (95%CI: 1.046 - 2.104), oral contraceptives (95%CI: 1.087 - 1.806), age less than 45 years old (95%CI: 1.069 - 1.828) were related with CIN., Conclusion: infection rate of HR-HPV is an independent risk factor of CIN, however, the history of trichomonas vaginitis, oral contraceptives and age less than 45 years old are related risk factors of CIN.

Introduction: An increasing number of HIV-1-infected women reaches the age of menopause. This infection is associated with a higher incidence of cervical squamous intraepithelial lesions (low-grade or LSIL, high grade or HSIL). The aim of our study was to describe the cervical disease in these patients during menopause., Patients and Methods: Retrospective study, identifying all Pap smears and colposcopy in HIV-1-infected postmenopausal women between 1995 and 2008, in our hospital., Results: Eighteen postmenopausal women, aged of 54 years (43-63), have HIV-1 infection since 7.5 years (2-25). Fifty-one pathological exams were reviewed in which 27 (50.98%) abnormal, including four (7.84%) ASC-US, 15 (29.41%) LSIL lesions, and seven (13.73%) HSIL. Ten patients had surgery (laser, conisation, hysterectomy) during the period. The evolution of cervical lesions was: stability in 40.48%, regression in 35.71% and progression in 23.81%. The median time to develop an HSIL at menopause was 5 years., Conclusion: In our study, postmenopausal HIV-1-infected women have most frequently LSIL and persistent. Monitoring of these postmenopausal women should be continued, the attitude to realise an initial HPV typing and confirmation of an abnormal annually Pap smear with colposcopic exam should be confirmed by larger study., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Oncogenic human papillomavirus (HPV) infection is the most important risk factor in cervical carcinogenesis cases; high viral loads, viral integration into the host genome, and gain of the telomerase-related genes, TERT and TERC, are all factors associated with progression to cancer. A recently developed multiparameter HPV 16/18 multiplex ligation-dependent probe amplification (MLPA) assay, which allows the simultaneous assessment of these factors, was applied to a series of 67 normal and (pre)malignant frozen uterine cervical samples, as well as to 91 cytological preparations, to test the ability of the MLPA assay to identify high-risk lesions on the basis of these factors. Validation was performed using quantitative PCR, the PapilloCheck and fluorescence in situ hybridization. Only 5 out of 37 normal tissue samples or low-grade cervical lesions (ie, CIN1 and condyloma) showed either an HPV16 viral load higher than 25 copies per cell, viral integration, and/or gain of one of the telomerase-related genes, whereas for the high-grade cervical lesions, one or more of these risk factors was found in 25 of 30 cases. The HPV MLPA assay showed a sensitivity of 83% and a specificity of 86% in frozen cervical specimens. Furthermore, the feasibility of the MLPA assay was shown for cytological samples, where in 57% of high-grade squamous intraepithelial lesion cases, the high-risk factors were detected using this assay.

Context and Objective: The human immunodeficiency virus (HIV) is frequently associated with high-grade intraepithelial neoplasia. Immunosuppression and high HIV viral load are the main risk factors for cervical intraepithelial neoplasia (CIN). The aim of this study was to determine the prevalence of CIN in HIV-infected women in Salvador, Bahia, Brazil, and to describe the risk factors in comparison with non-infected women., Design and Setting: Cross-sectional study at the AIDS Reference Center of Bahia and the Gynecological Outpatient Clinic of Fundação Bahiana para o Desenvolvimento da Ciência, in Salvador, Bahia, Brazil., Methods: Sixty-four HIV-infected women and 76 uninfected women from Salvador were enrolled between May 2006 and May 2007. Associations between CIN and presence of HIV infection, HIV viral load, proportion of T CD4+ lymphocytes and risk factors were evaluated. The independence of the risk factors was investigated using logistic regression., Results: CIN was more prevalent among HIV-infected women than in the control group (26.6% versus 6.6%; P = 0.01). The odds ratio for CIN among HIV-infected women was 3.7 (95% confidence interval, CI: 1.23-11; P = 0.01), after adjusting for the following variables: age at first sexual intercourse, number of partners, number of deliveries and previous history of sexually transmitted disease., Conclusion: The prevalence of CIN among HIV-infected women was significantly higher than among women without HIV infection. HIV infection was the most important risk factor associated with the development of cervical lesions.

The cellular transcription factor Brn-3a differentially regulates different human papilloma virus (HPV)-16 variants that are associated with different risks of progression to cervical carcinoma in infected humans. The upstream regulatory regions (URRs) of high- and intermediate-risk HPV-16 variants are activated by the cellular transcription factor Brn-3a, whereas the URR of a low-risk HPV-16 variant is not. In this study, we show in transfection assays that Brn-3a and the smoking-related substance nicotine produce stronger responsiveness of the URR of the low- and high-risk variants than with either factor alone, but not the intermediate-risk variant. We determined that this synergistic activity of Brn-3a/nicotine is due to two nucleotide differences in the URR, crucial for oncogenic E6/E7 transactivation. Mutant constructs in which the nucleotide residues were substituted alter Brn-3a/nicotine responsiveness. Importantly, women smokers with high levels of Brn-3a infected with low- or high-risk HPV-16 variants have augmented E6 levels, and were more frequently diagnosed with higher grades of cervical intraepithelial neoplasia (CIN) and cancer, as compared with non-smokers who were infected with similar variants and expressed similar levels of Brn-3a. Therefore, this study defines the specific interplay between the cellular transactivator Brn-3a, the environmental smoking-related substance nicotine and specific HPV variants in cervical carcinogenesis, and thus helps to explain why some women are susceptible to rapid CIN progression and cancer and others are not.

BD ProExC (ProExC) and Ki-67, both used as biomarkers for high-grade cervical intraepithelial neoplasia (HG CIN), yield discordant staining in some cervical biopsies. This study compared ProExC and Ki-67 expression in 197 cervical biopsies with consensus diagnoses (55 negative, 21 atypical squamous metaplasia, 61 low-grade CIN, and 60 HG CIN). Percentages of immunostained nuclei were evaluated by 2 pathologists yielding 68 (35%) cases with discordant ProExC/Ki-67 immunostaining for analysis. In 78% of cases the difference in staining involved <25% of lesional cells. This was noted across all morphologic diagnoses, being most frequent in HG CIN. Discordant staining involving >50% of lesional cells occurred in 22% of discrepant cases, being most frequent in atypical squamous metaplasia. Using staining in >50% of lesional nuclei as a positive result, positive/negative discordance occurred in 25 cases (13% of all cases) including 18% of HG CIN cases. Fourteen cases were ProExC+ (7 of which were strongly p16+) and 11 were Ki-67+ (6 of which were strongly p16+).

Objective: To examine the effects of dietary supplements on high-risk human papillomavirus (HPV) infection and cervical carcinogenesis., Methods: A multi-institutional cross-sectional study was carried out to examine whether dietary supplements were associated with the risk of cervical intraepithelial neoplasia (CIN). We enrolled 1096 women aged 18 to 65 years to participate in an HPV cohort study from March 2006 up to present. For this analysis, we included 328 HPV-positive women (166 controls; 90 CIN I and 72 CIN II/III). The details of each participant's routine dietary intake during the prior year were collected. Specific dietary supplements were classified into 5 categories, namely, multivitamins, multinutrients, vitamin C, calcium, and miscellaneous., Results: A higher HPV viral load was associated with an increased risk of CIN II/III (odds ratio [OR], 3.32; 95% confidence interval [CI], 1.54-7.16; P for trend 0.002). Dietary supplement use including multivitamins (OR, 0.21; 95% CI, 0.09-0.48), vitamins A (OR, 0.19; 95% CI, 0.07-0.53), C (OR, 0.24; 95% CI, 0.10-0.56), E (OR, 0.20; 95% CI, 0.07-0.53), and calcium (OR, 0.21; 95% CI, 0.08-0.50) was significantly associated with a lower risk of CIN II/III. The patients who took multivitamins and had a lower HPV viral load (<15.5 relative light units/positive control) had a significantly decreased frequency of CIN I (OR, 0.35; 95% CI, 0.14-0.87; interaction P = 0.925) and CIN II/III (OR, 0.11; 95% CI, 0.04-0.37; interaction P = 0.304)., Conclusions: The findings of this study suggest that dietary supplements may reduce the risk of CINs in women with high-risk HPV infection.

Background: Given the high burden of cervical cancer in low-income settings, there is a need for a convenient and affordable method for detecting and treating pre-cancerous lesions., Methods: Samples for comparing the accuracy of cytology, virology and histology were collected. Identification of HPV E6/E7 mRNA was performed using PreTect HPV-Proofer. HPV DNA detection was performed by GP5+/6+ PCR, followed by reverse line blot (RLB) for typing., Results: A total of 343 women, aged 25-60 years, attending gynaecological polyclinics in DR Congo were included for sample enrolment. The test positivity rate was conventional and liquid-based cytology (LBC) at cutoff ASCUS+ of 6.9 and 6.6%, respectively; PreTect HPV-Proofer of 7.3%; and consensus DNA PCR for 14 HR types of 18.5%. Sixteen cases of CIN2+ lesions were identified. Of these, conventional cytology identified 66.7% with a specificity of 96.2%, LBC identified 73.3% with a specificity of 96.9%, all at cutoff ASCUS+. HR-HPV DNA detected all CIN2+ cases with a specificity of 85.9%, whereas PreTect HPV-Proofer gave a sensitivity of 81.3% and a specificity of 96.6%., Conclusion: Both HPV detection assays showed a higher sensitivity for CIN2+ than did cytological methods. Detecting E6/E7 mRNA from only a subset of HR HPVs, as is the case with PreTect HPV-Proofer, resulted in a similar specificity to cytology and a significantly higher specificity than consensus HR HPV DNA (P<0.0001).