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Sweden has experienced an unexpected >30% increase in cervical cancer incidence among women with normal cytological screening results. We therefore performed a nationwide assessment of false-negative cytology before invasive cervical cancer. The Swedish national cervical screening registry identified 2,150 normal cytologies taken up to 10 years before 903 cases of invasive cervical cancer. The 27 cytological laboratories in Sweden were asked to rereview the slides, and all of them completed the rereview. One thousand nine hundred fifteen slides were retrieved and reviewed. Abnormalities were found in 30% of the slides, and the proportion of slides that had a changed diagnosis on rereview increased on average by 3.9% per sampling year during 2001–2016 (p < 0.03). We also asked for rereview of normal smears taken up to 42 months before a histopathologically diagnosed high-grade squamous intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS). 19/27 laboratories responded, and out of 6,101 normal smears taken before HSIL/AIS, 5,918 were retrieved and rereviewed. The diagnosis was changed in 25% of cases. In summary, we found an increasing time trend of false-negative smears taken before invasive cervical cancer. This indicates a decreased protection of normal cytology in the screening program supporting earlier findings that this is the main reason behind the recent Swedish increase in cervical cancer. We suggest that optimal cervical cancer control may be promoted by routine nationally coordinated rereview of negative smears before high-grade cervical lesions or invasive cervical cancer.

Introduction: Various Human papillomavirus (HPV) types cause cervical cancer, and represent the primary cause of cancer death in Africa and the second cause of most common cancers in Cameroon. Herein, we determined the prevalence of high-risk HPV types in women and associated cervical cytologic abnormalities in Yaounde, Cameroon. Methodology: A cross-sectional study targeting HPV-positive women aged 20 and over was conducted between March and June 2020 at the Saint Martin de Porres’ Health Centre in Yaounde. HPV tests were performed by PCR for detection of HPVs 16, 18, 33, and 45. The test was performed on 616 women using exfoliated cell specimens; then, we processed on cytological diagnosis with Pap smears on HPV positive specimens. Results: The HPV types tested were detected in 137 participants, of which 38.7% with multiple HPV infections, and the remaining part with single HPV infections of type HPV 16 (28.5%), HPV 18 (17.5%), HPV 33 (10.2%), and HPV 45 (5.1%). Cervical cytologic abnormalities were found in 69.34% of participants including: LSIL (49.63%), HSIL (15.32%), ASC-US (3.66%) and AGC (0.73%). Co-infections with HPV 16 and HPV 18 were significantly associated with HSIL (p = 0.001) lesions, while HPV 45 was more common in participants with normal cytology (p = 0.001). Cervical lesion occurrence was significantly associated with the number of sexual partners (p = 0.02) and history of oral contraceptive pill use (p = 0.001). Conclusions: Our results suggest that HPV 16 and 18 are predominant in Yaounde, and are associated with more severe precancerous lesions.

Failure to follow-up women after abnormal cervical screening could lead to cervical cancers, yet little is known about adherence to recommended follow-up after abnormal co-testing [cytology and high-risk human papillomavirus (hrHPV) testing]. We documented clinical management following cervical screening by co-testing in a diverse population-based setting. A statewide surveillance program for cervical screening, diagnosis, and treatment was used to investigate all cytology, hrHPV and biopsy reports in the state of New Mexico from January 2015 through August 2019. Guideline-adherent follow-up after co-testing required 1) biopsy within 6 months for low-grade cytology if positive for hrHPV, for high-grade cytology irrespective of hrHPV, and for HPV 16/18 positive results irrespective of cytology and; 2) repeat co-testing within 18 months if cytology was negative and hrHPV test was positive (excluding types 16/18). Screening co-tests (2015-2017) for 164,522 women were analyzed using descriptive statistics, Kaplan Meier curves, and pairwise comparisons between groups. Guideline adherence was highest when both cytology and hrHPV tests were abnormal, ranging from 61.7% to 80.3%. Guideline-adherent follow-up was lower for discordant results. Women with high-grade cytology were less likely to receive a timely biopsy when hrHPV-testing was negative (48.1%) versus positive (83.3%) (p < 0.001). Only 47.9% of women received biopsies following detection of HPV16/18 with normal cytology, and 30.8% received no follow-up within 18-months. Among women with hrHPV-positive normal cytology without evidence of HPV 16/18 infection, 51% received no follow-up within 18 months. Provider education and creation of robust recall systems may help ensure appropriate follow-up of abnormal screening results.

International audience; Unlabelled - For patients at high risk of anal cancer, annual screening strategies using invasive evaluation methods are stressful. According to a normal examination at baseline using simple and non invasive tests, the aim of the work was to quantify neoplastic events. Patients and method - Data from patients with a normal evaluation at the first visit were retrospectively extracted from a prospective database. The individual follow-up period was at least two years and three evaluations. Patients with abnormal cytology were assessed using high-resolution anoscopy and targeted biopsies. Results - A total of 182 subjects (F/M: 10/90, aged 48.1(10.6) years, HIV: 81%) were followed for 41(11) months. Anal cytology remained normal in 94 patients (52%), but high-grade anal neoplasms occurred in 28 patients (15%). Patients with a negative HPV16 status at baseline had cumulative probabilities of high-grade AIN of 0.4%(0.1%-1.9%), 2.6%(1.2%-5.9%) and 7.5%(4.5%-12.2%) after 1 year, 2 years and 3 years of follow-up, respectively. These probabilities were lower than those of patients with a positive HPV16 at baseline and those with a previous history of AIN. Conclusion - In patients with normal cytology and negative HPV16 at baseline, a three-year interval screening may be a less cumbersome alternative to traditional annual screening.

High-risk human papillomavirus type 16/18 (HPV16/18) genotyping is unable to accurately discriminate nonprogressive infections from those that will progress to cervical cancer. Our study aimed to assesses if additional testing either with liquid-based cytology (LBC) or the putative progression markers p16/Ki-67 and HPV16/18 E6 oncoprotein (E6) can improve the efficiency of HPV16/18 genotyping for triaging high-risk HPV (hrHPV)-positive women through better cancer risk stratification. Women attending colposcopy after positive HPV16/18 genotyping results within the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA) hrHPV-based screening study in Tlaxcala, Mexico, underwent further testing with LBC, p16/Ki-67 dual-stained (DS) cytology and E6. We calculated measures of test performance for detecting histologically confirmed cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and grade 3 or higher (CIN3+). A number of 475 (64.3%) of 739 HPV16/18-positive women had complete results for all tests. Triage positivity rates were 14.1%, 18.5% and 24.4%, for LBC, E6 and DS, respectively. Compared with LBC, DS had higher sensitivity (24.4% vs 60.0%) although lower specificity (87.0% vs 79.3%) for CIN3+ (P

Objectives: Few studies on human papillomavirus (HPV) have been conducted in Mongolia. This study was performed to evaluate the prevalent HPV genotypes and their associations with cytology and demographic and behavioral characteristics in Mongolian women with cervical abnormalities. Methods: Exfoliated cell samples of 100 women who had a previous history of cervical abnormality were collected. Cytological interpretation was conducted microscopically and HPV genotyping was performed using the Roche Linear Array test. Study questionnaires were completed. Results: Overall, 25 HPV genotypes were detected in 47% of participants, and the most prevalent were HPV 16, 52, 58, and 33. Cytological examination revealed 12% of participants had atypical squamous cells of undetermined significance (ASC-US), 8% had low-grade squamous intraepithelial lesions (LSIL), 7% had high-grade squamous intraepithelial lesions (HSIL), and 14% had squamous cell carcinoma (SCC), while 59% of women had a normal cytology. HPV 16 was the most common type among women with a normal cytology and cervical cancer. However, women with cervical abnormalities including LSIL and HSIL were predominantly infected with HPV 52. Moreover, women aged

Cervical microbiota composition is associated with cervical HPV infection and CIN severity. Previous studies only assessed the total association between cervical microbiota and HPV infections or CINs, and yet no study reported the direct and indirect associations between cervical microbiota and CINs mediated by HPV infection, respectively. The aim of this study was to investigate the direct and indirect associations between microbiotas and CIN severity. Cervical microbiota of 126 women with CIN 1− (normal cytology and CIN 1) and 40 with CIN 2+ (CIN 2 and CIN 3) were analyzed using Illumina sequencing based on the 16S rRNA gene. HPV was detected using a highly sensitive PCR primer set (SPF1/GP6+). Indirect effects of Pseudomonas stutzeri, Bacteroides fragilis, Lactobacillus delbrueckii, Atopobium vaginae, and Streptococcus agalactiae mediated by HPV infection on CIN status were observed. The directions of the direct and the indirect associations between CIN status and Ps. stutzeri were opposite. The directions of the direct and the indirect associations between CIN status and A. vaginae were the same. B. fragilis, L. delbrueckii, and S. agalactiae only had indirect association with CIN status. In summary, our study provided suggestive evidence that some microbial populations could have direct or indirect effects mediated by affecting HPV infection on CIN progression. Besides HPV infection, microbial community composition possibly plays a role in cervical carcinogenesis.

The distribution and prevalence of 33 high-, medium-, and low-risk HPV genotypes were surveyed in women aged between 15 and 54 years and with normal cytology in the biggest cities and regions in Bulgaria (viz., Sofia, Plovdiv, Varna, and Burgas) and in two smaller communities (viz., Pleven and Vidin). This survey was also intended to update previous data collected in 2012 and to assess the results of a national campaign to immunize all 12-year-old girls against HPV, which was also started in 2012. The GenoFlow HPV Array Test Kit was used to analyze HPV status in cervical samples collected in 2012-2016 from 5277 women who had visited 47 gynecological clinics across the study sites. HPV infection was confirmed in 1570 (29.8%). The most common infecting genotype was HPV-16, which was detected in 687 women (13%), followed by HPV-56 in 333 women (6.3%), HPV-33 in 209 cases (4%), and HPV-31 in 190 subjects (3.6%). This is the second study to assess the prevalence of HPV infection in larger Bulgarian cities including the capital and to draw attention to the unusually high proportion of specific infecting genotypes.

OBJECTIVE To inform impending postcolposcopy guidelines, this analysis examined the subsequent risk of CIN 3+ among women with a grade lower than CIN 2 (< CIN 2) colposcopy results, taking into account the referring results that brought them to colposcopy and cotest results postcolposcopy. METHODS We analyzed 107,005 women from 25 to 65 years old, recommended for colposcopy at Kaiser Permanente Northern California. We estimated absolute risks of CIN 3+ among women: (1) recommended for colposcopy (precolposcopy), (2) following colposcopy and with histology results < CIN 2 (postcolposcopy), and (3) with cotest results 12 months after a < CIN 2 colposcopy (return cotest). RESULTS After colposcopy showing < CIN 2 (n = 69,790; 87% of the women at colposcopy), the 1-year risk of CIN 3+ was 1.2%, compared with 6.3% at the time of colposcopy recommendation. Negative cotest results 1 year after colposcopy identified a large group (37.1%) of women whose risk of CIN 3+ (i.e.

Background:In human papillomavirus (HPV)-based screening, a repeat HPV test is often recommended for HPV-positive women with normal cytology (HPV-pos/cyt-neg), but its absolute risk of cervical precancer (CIN3+) over two screening rounds needs to be assessed.Methods:We compared the 5-year risk of HPV infection and CIN3+ in HPV-pos/cyt-neg women with a negative repeat HPV test to the risk in HPV-negative women with normal cytology (double negatives) in the POBASCAM cohort. We obtained histology data from the Dutch pathology registry (PALGA).Results:Human papillomavirus infection risk was 20.4% (19 of 93) in HPV-pos/cyt-neg, repeat HPV-negative women and 3.2% (294 of 9186; P

International audience; BACKGROUND:In French Guiana, cervical cancer is the second most frequent cancer in females. The objective of the present study was to describe the prevalence of HPV infections in women with normal cervical cytology living in the remote villages of French Guiana.METHODS:Before the study, the study team communicated in the remote villages on the importance of screening. All women from the target population were offered to participate. They signed informed consent during inclusion and then had a concomitant HPV-test and cervical smear. Only women with normal cytology and a good quality smear were analyzed. The detection of HPV-DNA was performed using the GREINER-BIO-ONE kit.RESULTS:Overall, 27.2% of women with normal cervical cytology had a positive HPV-test. There was a U-shaped evolution of prevalence with women over 50 years having the highest HPV prevalence, followed by the 20 to 29 years group. The most prevalent HPV genotypes were HPV 53(3.52%), 68(3.33%), 52(2.59%), 31(2.22%) and 16 (1.85%). The proportion of HPV 16 among HPV-infected women was 6.8%.CONCLUSIONS:HPV prevalence in cytologically normal women was very high. The most prevalent genotypes were very different from what is usually described in the world, and notably in South America.

The objective was to assess the diagnostic test accuracy of high-risk human papillomavirus (hrHPV) testing of self-collected urine and cervicovaginal samples for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). We recruited a convenience sample of women 25 to 65 years of age who were undergoing clinically indicated colposcopy at two medical centers in North Carolina between November 2016 and January 2019. Women with normal cytology results and positive hrHPV results were also recruited. Urine samples, self-collected cervicovaginal samples, provider-collected cervical samples, and cervical biopsy samples were obtained from all enrolled women. Samples were tested for hrHPV DNA using the Onclarity assay (Becton Dickinson, Sparks, MD). Biopsy samples were histologically graded as CIN2+ or

High-risk human papillomavirus cervical infection is currently a well-established cause of cervical cancer. However, only a few women with persistent infections will develop cervical precancerous and malignant lesions. Approximately 20% of all cervical cancers are attributable to non-16/18 serotypes. This study aims to evaluate the results of our clinical approach to women with this infection.We conducted an observational and prospective study from September 2012 to September 2017, which included women with isolated non-16/18 high-risk human papillomavirus infection (with normal cytology). After re-evaluation, two groups were compared: women with spontaneous regression of the infection and women with persistent infection. Clinical and demographic data were analysed as well as the rate of progression to precancerous and malignant lesions.We included 165 women, of which 121 were re-evaluated with co-test at least one year later. After re-evaluation, 13.2% of women revealed precancerous lesions but only two (1.7%) of them presented high-grade squamous intraepithelial lesions. Sixty-seven women (55.4%) showed spontaneous regression of the infection and 54 women (44.6%) maintained it. Women with persistent infection developed more precancerous lesions (27.8%; p0.001) and high-grade squamous intraepithelial lesions (3.7%; p0.001). There was also an association between persistent infection and postmenopausal status.Human papillomavirus 16/18 cervical infection is associated with higher risk of cervical cancer when compared with other serotypes.Re-evaluation with co-test one year after the diagnosis of isolated non-16/18 human papillomavirus infection seems to be a reasonable approach.Introdução: O cancro cervical é causado pelo papiloma vírus humano de alto risco. No entanto, apenas algumas mulheres com infeções persistentes desenvolvem lesões pré-malignas e malignas. Aproximadamente 20% destas neoplasias são causadas por serotipos que não os 16 e 18. Este estudo surge com o objetivo de avaliar a nossa prática clínica neste âmbito. Material e Métodos: Realizámos um estudo observacional e prospetivo entre setembro de 2012 e setembro de 2017, com inclusão de mulheres com infeção cervical isolada com papiloma vírus humano de alto risco, excluindo os serotipos 16 e 18 (com citologia negativa). Após reavaliação, comparámos dois grupos: mulheres que apresentaram resolução espontânea da infeção e mulheres com infeção persistente. Foram analisados dados clínicos e demográficos bem como a taxa de progressão para lesões precursoras e malignas. Resultados: Incluímos 165 mulheres e reavaliámos com co-teste 121 delas com pelo menos um ano de intervalo. Após reavaliação, 13,2% desenvolveram lesões precursoras, mas apenas duas (1,7%) foram consideradas de alto grau. Sessenta e sete mulheres (55,4%) apresentaram resolução espontânea da infeção e 54 (44,6%) mantiveram-na. As mulheres com infeção persistente desenvolveram mais lesões precursoras (27,8%; p0,001) e de alto grau (3,7%; p0,001). Constatou-se uma associação entre a persistência da infeção e pós-menopausa. Discussão: A infecção cervical com serotipos 16/18 associa-se a uma maior risco de desenvolvimento de cancro cervical quando comparada com outros serotipos. Conclusão: A reavaliação com co-teste um ano após o diagnóstico de infecção cervical isolada com papiloma vírus humano de alto risco, excluindo os serotipos 16 e 18, parece ser uma abordagem adequada.

No study examined the frequency of human papillomavirus (HPV) genotypes by surface plasmon resonance (SPR) in southwest China. This was a cross-sectional survey (The Second Affiliated Hospital of Kunming Medical University, 10/2010 to 12/2011) in 150 patients who were hospitalized or volunteered for cervical cancer (CC) screening. A HPV typing kit was used to detect 24 types of HPV by the SPR technique. The HPV-positive rate was 34.8% in women with normal cytology and 92.9% in women with CC. The frequency of HPV16 increased from 9.4% for women with normal cytology to 28.9% for cervical intraepithelial neoplasia (CIN)1, 41.4% for CIN2, 54.1% for CIN3, and 71.4% for CC (p < 0.001). The frequency of HPV18 increased from 0% for women with normal cytology to 2.6% for CIN1, 3.4% for CIN2, 5.4% for CIN3, and 21.4% for CC (p = 0.03). HPV40 was only found in one patient with CC (p = 0.04). There was no relation between HPV genotype and women’s age. In Kunming (southwest China), the frequency of HPV infection was 74.0% among women who underwent CC screening. HPV16 and HPV18 were the two most frequent genotypes. SPR could be of value for the screening of HPV infection.

Primary human papillomavirus (HPV)–based cervical screening will be introduced in the Netherlands in 2016. We assessed the 5-year cervical (pre)cancer risk of women with different combinations of HPV and cytology test results. Special attention was paid to risks for cervical intraepithelial neoplasia grade 3 and 2 or more (CIN3+/2+) of HPV-positive women with a negative triage test, because this determines the safety of a 5-year screening interval for HPV-positive, triage test–negative women. In addition, age-related effects were studied. A total of 25,553 women were screened by HPV testing and cytology in a screening setting. Women were managed on the presence of HPV and/or abnormal cytology. Five-year cumulative incidences for CIN3+/2+ were calculated. Five-year CIN3+(2+) risk was 10.0% (17.7%) among HPV-positive women. When stratified by cytology, the CIN3+(CIN2+) risk was 7.9% (12.9%) for women with normal cytology and 22.2% (45.3%) for women with equivocal or mildly abnormal (i.e., BMD) cytology. For HPV-negative women, the 5-year CIN3+(2+) risk was 0.09% (0.21%). Additional triage of HPV-positive women with normal cytology by repeat cytology at 12 months showed a 5-year CIN3+(2+) risk of 4.1% (7.0%). HPV-non 16/18-positive women with normal cytology at baseline had comparable risks of 3.5% (7.9%). HPV-non 16/18-positive women with normal baseline cytology and normal repeat cytology had a 5-year CIN3+ risk of 0.42%. No age-related effects were detected. In conclusion, HPV-positive women with normal cytology and a negative triage test, either repeat cytology after 12 months or baseline HPV 16/18 genotyping, develop a non-negligible CIN3+ risk over 5 years. Therefore, extension of the screening interval over 5 years only seems possible for HPV screen–negative women. Cancer Prev Res; 8(6); 502–8. ©2015 AACR.

International audience; BACKGROUND: Cervical cancer prevention using cervical cytology is insufficiently sensitive, a significant proportion of HPV-infected women having normal cytology. The objective of the present study was to try to identify factors associated with abnormal cytology in HPV-infected women living in remote areas of French Guiana.METHODS: A study was conducted in women aged 20-65 years having HPV infections confirmed by HPV DNA detection using the GREINER-BIO-ONE kit. In addition to HPV testing, cytology was performed and classified as normal or abnormal. Demographic and life history variables, and infecting genotypes were compared between the normal and abnormal cytology groups.RESULTS: None of the demographic and life history variables were associated with cytology results. HPV genotype 53 was significantly associated with absence of cytological abnormalities whereas HPV 52, 58, 16 and perhaps 33 and 66 were independently associated with a greater risk of cytological abnormalities. When grouping HPV genotypes in different species, only species 9 (HPV 16, 31, 33, 35, 52, 58, 67) was significantly associated with abnormal cytology AOR = 5.1 (95% CI = 2.3-11.2), P

Background: The aetiological relationship between human papillomavirus (HPV) infection and cervical cancer (CC) is widely accepted. Our goal was to determine the prevalence of HPV types in Mexican women attending at the Mexican Institute for Social Security from different areas of Mexico. Materials and Methods: DNAs from 2,956 cervical samples were subjected to HPV genotyping: 1,020 samples with normal cytology, 931 with low-grade squamous intraepithelial lesions (LGSIL), 481 with high grade HGSIL and 524 CC. Results: Overall HPV prevalence was 67.1%. A total of 40 HPV types were found; HPV16 was detected in 39.4% of the HPV-positive samples followed by HPV18 at 7.5%, HPV31 at 7.1%, HPV59 at 4.9%, and HPV58 at 3.2%. HPV16 presented the highest prevalence both in women with altered or normal cytology and HPV 18 presented a minor prevalence as reported worldwide. The prevalence ratio (PR) was calculated for the HPV types. The analysis of PR showed that HPV16 presents the highest association with CC, HPV 31, -33, -45, -52 and -58 also demonstrating a high association. Conclusions: The most prevalent HPV types in cervical cancer samples were -16, -18, -31, but it is important to note that we obtained a minor prevalence of HPV18 as reported worldwide, and that HPV58 and -52 also were genotypes with an important prevalence in CC samples. Determination of HPV genotypes is very important in order to evaluate the impact of vaccine introduction and future cervical cancer prevention strategies.

Background: Urine sampling may offer a less invasive solution than cervical sampling to test for human papillomavirus (HPV) for HPV vaccine impact monitoring. Methods: Paired samples of urine and exfoliated cervical cells were obtained for 89 women with history of high-risk (HR) HPV-positive normal cytology in Bhutan. Urine sampling protocol included self-collection of first-void urine immediately into a conservation medium and procedures to optimize DNA yield. Colposcopical abnormalities were biopsied. Two HPV assays were used: a multiplex type-specific PCR (E7-MPG) and a less analytically sensitive GP5+/6+ PCR followed by reverse line blot. Results: HPV positivity for 21 types common to both assays was similar in urine and cells by E7-MPG (62.9% and 57.3%, respectively, p = 0.32) but lower in urine by GP5+/6+ (30.3% and 40.4%, p = 0.05). HPV6/11/16/18 positivity did not significantly differ between urine and cells by either assay. Sensitivity of urine (using cells as gold standard) to detect 21 HPV types was 80% and 58% for E7-MPG and GP5+/6+, respectively, with specificity 61% and 89%. HPV type distribution in urine and cells was similar, regardless of assay. The 5 detected CIN3+ were HR-HPV positive in cells by both assays, compared to 4 and 3 by E7-MPG and GP5+/6+, respectively, in urine samples. Conclusion: For the monitoring of vaccine impact, we demonstrate validity of a urine sampling protocol to obtain HPV prevalence data that are broadly comparable to that from cervical cells. However, detection of HPV in urine varies according to assay sensitivity, presumably because low level infections are frequent.

Objective To determine the distribution of HPV-16 variants among Paraguayan women with different grades of cervical lesions. Methods Sixty-seven HPV-16-positive cervical samples obtained from women attending health centers in Paraguay between March 2007 and April 2009 were examined, including 29 low-grade squamous intraepithelial lesion (LSIL), 29 high-grade squamous intraepithelial lesion (HSIL), 4 cervical cancer, and 5 normal cytology samples. The specimens were analyzed by PCR-directed sequencing of a 364-bp fragment of the long control region of HPV-16, and a phylogenetic tree was compiled with MEGA 5.0 software. Results Most HPV-16 variants belonged to the European branch (82%); these variants were detected among 25 of 29 women with LSIL, 22 of 29 women with HSIL, 3 of 4 women with cervical cancer, and all women with normal cytology. Two isolates yielded new variants of the European branch with nucleotide substitutions at positions A7752C and A7810T. Non-European variants, such as African type 1 (1.5%) and Asian-American (16.5%), were detected only among women with cervical lesions (4/29, LSIL; 6/29, HSIL; 1/29, cervical cancer). These variants had at least 6 nucleotide substitutions adjacent to or within transcription factor binding sites. Conclusion All branches of HPV-16 variants were detected among Paraguayan women with cervical lesions.

Objectives: To investigate the role of cytokeratin-19 fragment (CYFRA21-1) in cervical lesions screening in high-risk hu­man papillomavirus (HR-HPV) infected women. Material and methods: The study was a retrospective study. First, the results of CYFRA21-1, cytology (TCT), and HR-HPV examinations of 1039 outpatients from gynecology department in Tumor Hospital Affiliated to Xinjiang Medical University were collected. Then, the data was analyzed using a series of statistical methods. Results: There was a correlation between CYFRA21-1 levels and HPV-DNA load in HR-HPV infected women (r s = 0.711, p = 0.015). CYFRA21-1 levels and positive rate increased along with deepening of cervical cell lesions. In HR-HPV infected women, there was a statistically significant difference (t = 6.022, p < 0.001) in CYFRA21-1 levels between the group with cytological lesions (4.87 ± 1.58 ng/mL) and the group with normal cytology (2.52 ± 0.96 ng/mL). Positive rates of CYFRA21-1 in the two groups were 62.06% and 7.83%, respectively, and also exhibited statistically significant differences ( χ 2 = 74.624, p < 0.001). When diagnosing cytological lesions via CYFRA21-1 in HR-HPV infected women, sensitivity was 62.07%, specificity was 92.17%, positive predictive value was 88.89%，negative predictive value was 70.67%. Compared to CYFRA21-1 negative women, cytological lesions were detected 19.273 times more often in CYFRA21-1 positive women. Conclusion: CYFRA21-1 could provide a reference idea for further diagnosis of women who are infected with HR-HPV but whose cytology is normal.

WOS: 000305386800011, PubMed ID: 22711352, The age-specific human papillomavirus (HPV) seroprevalence and HPV type distribution in women with normal cervical cytology were studied. Cervical smear samples obtained using liquid-based smears from 582 clinically healthy women aged between 15 and 68 years from five centers from four different regions of Turkey, were studied between February 2010 and January 2011. Overall, 530 of the women with normal cytology were included and the samples were analyzed for the presence of HPV by AmpliTaq. Positive samples were typed further for 37 different HPV genotypes by a line blot assay. HPV was positive in 17.9% of the women. HPV prevalence was highest in the age group of 2529 years (31.8%), and decreased with increasing age. HPV 16 was the most common type (3.6%) followed by type 6 (2.6%) and type 45 (2.2%). Types 11 and 18 were rare (0.6% and 0.4%, respectively). Among the risk factors, number of sexual partners and parity were positively correlated with HPV positivity. In the present study, a large number of sex partners and high parity increased the risk for HPV infection. The age-specific distribution of HPV in women with normal Pap smears did not show a U-shaped curve in contrast to European countries and the USA. J. Med. Virol. 84: 12421247, 2012. (C) 2012 Wiley Periodicals, Inc.

We examined the prevalence of human papillomavirus (HPV) infection in a sample of Brazilian women presenting normal cervical cytology. Possible interactions between patient characteristics and HPV infection were analyzed in order to provide background data to improve cervical cancer screening and prophylaxis. Cervical samples of 399 women, received for routine evaluation in the Health Department of Ouro Preto, MG, Brazil, were subjected to HPV-DNA testing by PCR with MY09/11 primers. HPV-positive specimens were typed by RFLP. A structured epidemiological questionnaire was administered to each woman. HPV prevalence among these cytologically normal women was 11%. Twelve viral types were detected, the most common being HPV-16, -6, -61, -83, and -66. HPV was more prevalent in younger women; high-risk viral types were detected in 61% of the infected women and 27% of the infected women had multiple HPV infections. Significant associations of HPV infection were found with age, literacy, residence, marital status, lifetime number of sexual partners, and parity. We detected a great diversity of HPV types in women with normal cytology. This kind of information about local populations is useful for HPV prevention and vaccination strategies.

Summary Objective To determine the prevalence of human papillomavirus (HPV) infection and genotype distribution in Mexican women with similar lifestyles from two geographical regions who receive medical care from the Mexican Navy Health System, and to identify the associated sociodemographic and reproductive characteristics. Methods Cervical swabs from 671 women, beneficiaries of the Mexican Navy Health System, from two distinct southern coast regions of Mexico, were analyzed. Data were obtained regarding sociodemographic variables and sexual and reproductive history. For HPV detection and typing, PCR with general primers and direct sequencing were performed on extracted DNA. Association with clinical variables was evaluated. Results Most patients had a normal cytology or low-grade intraepithelial neoplasia. A high prevalence of HPV was found (43.6%), with a significant difference between the two regions studied from the southwest Pacific coast of Mexico (37.6% in Acapulco, Guerrero vs. 49.7% in Lazaro Cardenas, Michoacan). Some differences were also found associated to HPV type distribution, particularly related to genotypes 18, 58, and 53. Factors influencing these differences could not be identified with the analysis of typical risk factors linked to the acquisition of an HPV infection. Conclusions Regional differences in HPV prevalence and distribution show an apparent geographic boundary between the studied populations that deserves further analysis, taking into account other factors such as those related to the sexual partners.

We investigated neutralizing antibodies to human papillomavirus type 16 (HPV-16) in serum and cervical washes from 84 women with normal cytology or cervical disease. Serum neutralizing antibodies were detected in 78 % of women infected at the cervix with HPV-16, compared with 35 % (P=0.002) of women infected with HPV-16-related types (α9 HPV types), 14 % (Prs=0.97;P=0.032). Cervical neutralizing antibodies were detected in 38 % of women with HPV-16 infection and in 17 % of women infected with the HPV-16-related type HPV-31. Cervical neutralizing antibodies correlated with HPV-16 infection (rs=0.95;P=0.08), but not with cervical disease. Serum and cervical HPV-16 antibody responses were not affected significantly by human immunodeficiency virus type 1 infection. In conclusion, serum and cervical HPV-16-neutralizing antibodies were found to correlate with HPV-16 infection, but not with cervical disease.

Evaluation of promoter methylation of the death-associated protein kinase (DAPK) gene and HPV and EBV infections in cervical cells from patients with normal cytology and colposcopy.Twenty women, who had been patients at the Institute of Gynecology of the Federal University of Rio de Janeiro (UFRJ) for routine examinations and who showed normal cytology and colposcopy, were selected for this work. Cervical brushings were used for DNA extraction, and the analysis of methylation patterns of the DAPK gene was done through chemical modification with sodium bisulfite. Analysis of viral infection was done using polymerase chain reaction (PCR).Of the 20 patients studied, six (30%) presented methylation of the DAPK gene, five (25%) presented infection with EBV and three (15%) presented coinfection with HPV/EBV. Associating methylation with viral infection, we found methylated DAPK in one patient (16%) with EBV, in two patients (33%) with co-infection and in three patients (50%) with no viral infection.In the present study, we verified, for the first time, the methylation pattern of the DAPK gene in cervical smears from patients with normal cytology and colposcopy. The results also showed the presence of viral infections in these patients. EBV infection, irrespective of whether associated with HPV or not, may contribute to cervical carcinogenesis as a cofactor. Methylation of the DAPK gene is associated with cell transformation, suggesting that DAPK methylation might be an important marker for the development of cervical epithelial neoplasias.

Objectives. To examine the prevalence of Human papillomavirus and Chlamydia trachomatis DNA in cervical samples among women with normal and abnormal cervical cytology from La Plata, Argentina. Methods. Two hundred and seventy-nine women (200 with cervical neoplasia or ICC and 79 women with normal cytology) provided cervical samples for the detection of HPV and C. trachomatis DNA by PCR-based assays. Results. HPV DNA increased with the cervical lesion severity, ranging from 30% among women with normal cytology to 99–100% among women with HSIL or ICC. C. trachomatis DNA prevalence increased from low levels in women with normal cytology (11%) to 47% in those with HSIL, but was uncommon among ICC patients (20%). Among women with normal cytology, C. trachomatis prevalence was higher in HPV DNA positive (12.5%) than HPV DNA negative women (10.9%), but this difference was not significant. Conclusions. HPV prevalence in the general population is slightly higher than those reported for other developing countries. C. trachomatis DNA positivity was associated with a higher risk of both LSIL and HSIL lesions, but not with ICC.

Infection with human papillomavirus (HPV) could affect genesis of both cervical and esophageal cancers. The type-specific distribution of HPV in cervical cytology abnormalities of women has remained unclear in Shantou, an esophageal cancer high-incidence area of China. Data from 22,617 women who were subjected to cervical HPV DNA testing with simultaneous cervical cytological examination during 2009-2013 were therefore here retrospectively evaluated in a hospital-based study. Overall, 16.2% (3,584/22,114)of women with normal cytology were HR-HPV positive, with HPV-52 (4.07%) as the most common type followed by -16 (3.63%), and -58 (2.46%). Prevalence of HR-HPV was 50.3% (253/503) in women with cervical cytological abnormalities, of which in ASC-H 71.4%, ASC-US 39.1%, HSIL 80.3% and LSIL 73.7%. HPV-58 (14.12%) was the most common type for all cervical cytological abnormalities, followed by HPV-16 (13.72%), and -52 (12.72%), while the more common HPV-16 type in ASC-H (42.9%) and HSIL (36.1%), HPV-52 and -58 were the most common types for ASC-US (10.3%) and LSIL (25%), respectively. Multiple HPV co-infections were identified in 33.2% (84/253) cytology abnormalities with positive HR-HPV, and the highest prevalence of HPV-58/16 combination in HSIL (28.6%, 6/21) was observed. Our data indicated a relative high prevalence of HPV-58 and -52 in women with cervical cytological abnormalities, which should be considered in the development of next-generation vaccines for Shantou.

Commentary on: Ronco G, Dillner J, Elfstrom KM, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 2014;383:524–32.[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Over the past 20 years, cervical cancer screening guidelines have evolved from advising performance of cervical cytology on every sexually active woman every year, to advising no screening on women under the age of 21 years and use of cervical cytology every 3 years only in women aged 30–65 years with an intact cervix.1 Many clinicians use human papillomavirus (HPV) testing with cervical cytology to triage abnormal cytology. Others have begun to use HPV alongside normal cytology. The data to support this strategy was based solely on protection from cervical … [1]: {openurl}?query=rft.jtitle%253DLancet%26rft.volume%253D383%26rft.spage%253D524%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252813%252962218-7%26rft_id%253Dinfo%253Apmid%252F24192252%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/S0140-6736(13)62218-7&link_type=DOI [3]: /lookup/external-ref?access_num=24192252&link_type=MED&atom=%2Febmed%2F19%2F4%2F148.atom [4]: /lookup/external-ref?access_num=000331136400028&link_type=ISI

In a retrospective case–control study, we investigated high-risk HPV DNA presence by general primer GP5+/6+ PCR in the last normal cervical smear in the patient archives (i.e. baseline smear) of 57 women who later developed cervical cancer. Also, normal cervical smears of 114 age-matched control women were analysed. High-risk HPV DNA was detected in 37 of the 57 (65%) baseline smears of the case women, and 7 (6%) of 114 smears of the control women (OR 28, 95% Cl 11–72). The HPV positive subsequent smears and cervical cancer biopsies of the case women contained the same HPV type as was detected in the baseline smear. After cytological revision, the baseline smears of 48 case women (84%) were reclassified as abnormal, 33 (69%) of which scored high-risk HPV DNA positive. Ultimately, an undisputable normal baseline smear was found in only 10 case women. In 7 (70%) of them this smear was HPV positive, whereas only 7 (7%) of 104 revised, undisputable normal smears of control women were high-risk HPV positive (OR 32, 95% Cl 6.8–153). The results showed that (1) high-risk HPV presence precedes abnormal cytology in women who develop cervical cancer, and (2) high-risk HPV testing signals false-negative smears of women at risk of cervical cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com

Various methods have been proposed for HPV detection and typing. Prevalence and distribution among types have varied depending upon the methods used and the populations studied. We have applied the polymerase chain reaction (PCR) followed by a Restriction Fragment Length Polymorphism (RFLP) analysis using the MY09/MY11 primers for detection of HPV in cervicovaginal lavages obtained from 323 patients who were referred to our Clinical Department either for genital complaints or an abnormal PAP smear. We assessed (i) the prevalence of HPV and (ii) the reliability of RFLP-typing. For the latter, 35 PCR-HPV products were sequenced. HPV-DNA was detected in 40/197 (20.3%) patients with normal cytology, 86/111 (77.5%) with LSIL and 11/15 (73.3%) with HSIL. HPV-16 was the most common type detected in normal cervical cytology samples (10/40, 25%), whereas HPV 16 and 18 were detected in 36/97 (37.1%) of the LSIL and HSIL patients, evidencing the presence of these high-risk HPV types not only in malignant conditions. Results obtained after partial nucleotide sequencing confirmed the results obtained by RFLP analysis. In this study, a putative new HPV fragment (GA6053) was identified. Its closest homology to other known HPV types is 73.8% to HPV-62, 73.0% to HPV-61 and 67.7% to HPV-18. The use of degenerate primers, in conjunction with RFLP, proved to be a reliable method for HPV detection and typing.

Objectives: This study investigates the potential value of Raf kinase inhibitor protein (RKIP) as a marker of normal squamous cells in ThinPrep slides. RKIP was evaluated for its ability to distinguish between normal and abnormal cervical samples in the context of human papillomavirus (HPV) infections. Study Design: A total of 316 ThinPrep samples were taken from women with normal and abnormal cervices. ThinPrep slides were Papanicolaou stained and reported. Residual samples were used for RKIP immunostaining and HPV PCR-based sequencing. Results: RKIP expression was seen in both nuclei and cytoplasm in 83.7% of samples. RKIP expression was highest (84.6%) in samples with a diagnosis of high-grade squamous intraepithelial lesion (HSIL) or worse; expression was lower in low-grade squamous intraepithelial lesions (73%) and was lowest in samples with normal cytology (p = 0.0023). A total of 74% of HPV-infected ThinPrep samples were immunopositive, and 67% of samples that did not harbor HPV were also immunopositive (p = 0.414). Sensitivity and specificity of RKIP were 84.6 and 34.6%, respectively, for the detection of samples with HSIL or worse. Conclusions: This study showed that RKIP expression may be of some value as a marker for abnormal cervical cells. Combined RKIP expression and HPV testing could improve the identification of samples with abnormal cytology.

The PapilloCheck® assay was compared with the Digene HC2 HPV DNA assay for the detection of 13 high-risk human papillomaviruses (HPV) in 240 samples, including 181 cervical scrapes and 59 anal scrapes. Overall, 75 (30.5%) samples were positive by the Digene HC2 HPV DNA assay: 34 (18.8%) cervical scrapes and 41 (69.5%) anal scrapes. By considering only the 13 high-risk HPV types detected by the Digene HC2 HPV DNA assay, 66 (27.5%) samples were positive by the PapilloCheck® assay: 27 (14.9%) cervical scrapes and 39 (66.1%) anal scrapes. Concordant results between the two assays were obtained for 225 (93.8%) samples with a Kappa coefficient value of 0.85, indicating an excellent agreement. By considering all the HPV types detectable by the PapilloCheck® assay, the overall prevalence of HPV was 34.2% (82/240): 21.0% (38/181) in cervical scrapes and 74.6% (44/59) in anal scrapes. Among the samples positive by the PapilloCheck® assay, a multiple HPV infection (2–9 HPV types) was identified in 43 of 82 (52.4%) samples, including 7 of 38 (18.4%) cervical samples, and 36 of 44 (81.8%) anal samples. The prevalence of high-risk HPV, as determined by the PapilloCheck® assay, was 17.6% (36/205) in samples with normal cytology, 83.9% (26/31) in samples with low-grade squamous intraepithelial lesions or atypical squamous cells of undetermined significance, and 100% (4/4) in samples with high-grade squamous intraepithelial lesions. The results obtained indicate that the PapilloCheck® assay may be considered as a reliable screening test for HPV detection and typing. J. Med. Virol. 83:1377–1382, 2011. © 2011 Wiley-Liss, Inc.

This study analyzed the prevalence of human papillomavirus (HPV) in cervical specimens obtained from women with normal cytology and with cervical cancer, in order to evaluate their correlation with health status and demographic characteristics, as well as sexual and reproductive activity in women treated at a cancer reference hospital in Natal, Northeast Brazil. A total of 158 women were divided into 2 groups according to their health status: group I comprised 110 women with normal cytology, and group II comprised 48 women with cervical cancer. Cervical smears were analyzed by cytological or histopathological examination for the detection of cytological alterations, and by PCR for HPV DNA detection using MY09/11 primers, followed by HPV genotyping by dot blot hybridization. Results showed overall HPV prevalence to be 24.5% in group I, with 19.1% of patients having single infection and 5.4% double infection. The HPV prevalence in group II was 85.4%, with 79.2% of patients having single and 6.2% double infection. We identified 10 different HPV genotypes, most with high oncogenic potential. HPV 16 was the most prevalent genotype in the two studied groups, followed by HPV 58 and HPV 18. High-risk HPV genital infection, chronological age, ethnicity, early onset of sexual and reproductive activities, multiple sexual partners and smoking increased the risk for cervical cancer.

Background: No accurate estimates of cervical cancer incidence or mortality currently exist in Georgia. Nor are there any data on the population-based prevalence of high-risk (HR) human papillomavirus (HPV) infection, which, in the absence of good-quality screening, is known to correlate with cervical cancer incidence. Methods: We obtained cervical cell specimens from 1309 women aged 18–59 years from the general population of Tbilisi, and also from 91 locally diagnosed invasive cervical cancers (ICC). DNA of 44 HPV types was tested for using a GP5+/6+-based PCR assay. Results: In the general population (of whom 2% reported a previous Pap smear) HPV prevalence was 13.5% (95% CI: 11.6–15.9), being highest in women aged 25–34 years (18.7%) and falling to between 8.6% and 9.5% for all age groups above 34 years. HR HPV prevalence was 8.6% overall, being 6.8% and 38.9% among women with normal and abnormal cytology, respectively. HPV45 (1.6%) was the most common type in women with normal cytology, whereas HPV16 predominated among women with cervical abnormalities (including 7 of 10 histologically confirmed cervical intraepithelial neoplasia 2/3) and among ICC (57.6%). The next most common types in ICC in Georgia were HPV45 and 18 (13.2 and 11.0%, respectively). Conclusions: We report a relatively high burden of HPV infection in Tbilisi, Georgia. Improving cervical cancer prevention, through screening and/or HPV vaccination, is an important public health issue in Georgia, where 70% of ICC are theoretically preventable by HPV16/18 vaccines.

Contains fulltext : 89056.pdf (Publisher’s version ) (Closed access) OBJECTIVE: In this study, we investigated the prevalence of human papillomavirus 16 (HPV-16) variants in Honduran women with normal cytology and with dysplasia and cervical cancer. METHODS: Samples identified as positive for HPV-16 by SPF10-LiPA were tested for intratypic subtypes and variants by analysis of the E6/E7 region using a novel reverse hybridization assay (line probe assay). RESULTS: We found that most infections in all clinical groups belong to the E6 European variants, suggesting that HPV-16 non-European variants do not represent an additional factor associated with increased occurrence of high-grade cervical lesions in the studied population. Among the 106 HPV-16-positive women analyzed, E-350G was the most prevalent variant in all different disease stages, being present in 18% of cervical cancer, 13% of cervical intraepithelial neoplasia grade III (CIN III), 5% of CIN II, 5% of CIN I, and 20% of control samples. Mixed variants of HPV-16 infections were detected in 7.7% of the samples, mostly in women with normal cytology. CONCLUSIONS: This study shows for the first time the diversity of HPV-16 variants in cervical samples of Honduran women. 01 april 2010

The cytological patterns in bile were compared with the histological findings in concomitant specimens from liver transplants. In cases where cytology showed a moderate (n = 10) or high cell density (n = 8), histology demonstrated rejection in 14 of 18 specimens and cholangitis in 4. When the cell density was low (n = 22), histology was nearly normal in 3 specimens and showed cholangitis in 9, while rejection was observed in 10 specimens. Cell density in bile did not correlate quantitatively with the severity of cellular infiltration in the portal triads or with the percentage of bile ducts attacked by inflammatory cells. The results of the present study support our hypothesis that an increased concentration of cells in bile is indicative of liver transplant rejection (sensitivity 58%), while normal cytology does not rule out the possibility of rejection (specificity 75%).

Patients with abnormal Pap smears underwent repeat Pap smear, colposcopy, biopsy, and human papilloma virus (HPV) typing to identify the presence of CIN and to assess the correlation of HPV type to grade of CIN and behavior of CIN. A total of 334 patients underwent evaluation and typing with Southern blot methodology. Fifty-five percent (185) of the patients demonstrated HPV viral sequences; 98 of the 185 positive patients demonstrated HPV types 16, 18. The presence of HPV sequences was not associated with a higher frequency of positive cytology of CIN II or III. High-grade CIN (II or III) was seen in 17.3, 13.5, 13.8, and 10.7% of patients with HPV 16, 18; 6, 11; 31, 33, 35; or no HPV sequences. Of 52 patients with normal cytology and biopsy revealing less than or equal to CIN I, no patients with types 6, 11, 3/5 patients with 31, 33, 35, 3/15 patients with 16, 18, and 2/23 patients with no HPV sequences progressed to greater than or equal to CIN II. These data do not support a role for HPV typing in predicting the initial histology. Typing may be of some value in monitoring patients with low-grade lesions.

Contains fulltext : 80440.pdf (Publisher’s version ) (Closed access) OBJECTIVE: This study was aimed at estimating type-specific HPV prevalence and its cofactors among Honduran women with normal cytology in order to provide valuable information to health policymakers about the epidemiology of this important sexually transmitted infection. METHODS: A total of 591 women with normal cytology from Tegucigalpa, Honduras were interviewed and tested for HPV using the SPF10 LiPA25. A structured epidemiological questionnaire was administered to each woman. RESULTS: The overall HPV prevalence was 51%. Twenty-three types of HPV were detected; HPV 16, 51, 31, 18, and 11 were the most common. The highest prevalence of cancer associated HPV types (15.0%) was found in the women less than 35 years. Besides the association with age, the main independent predictors of HPV infection were the lifetime number of sexual partners and having a low socioeconomic status and less than 5 previous Pap smears. CONCLUSIONS: In the population studied, there was a broad diversity of HPV infections, with high-risk types being the most common types detected. The establishment of a well-characterized population with regard to the community prevalence of type-specific HPV infection will provide a valuable baseline for monitoring population effectiveness of an HPV vaccine.

The influence of HAART on the evolution to cervical squamous intraepithelial lesions (SIL) among HIV(+) women with a normal cytological test in the HAART era was studied. A retrospective cohort study (1997-2005) of HIV-infected women treated with HAART was conducted. Those with a normal cervical cytology (Papanicolaou test) and at least one subsequent test were included. Survival (time until diagnosis of SIL), univariate, and multivariate analyses were performed. A total of 133 HIV-infected patients treated with HAART were included. The incidence of SIL was 35% (47 patients). SIL was diagnosed in 36 of 110 (33%) patients with a baseline and final immunological status of >200 CD4 cells/microl and in 6 of 9 (67%) patients with a baseline and final immunological status of < or =200 CD4 (OR: 0.24, 95% CI: 0.06-1.03, p = 0.041). SIL was diagnosed in 10 of 60 (17%) patients with an undetectable baseline and final HIV viral load and in 36 of 70 (51%) patients with a detectable HIV viral load (OR: 0.19, 95% CI: 0.07-0.46, p < 0.001). A high incidence of SIL (cancer precursor lesions) was observed among HIV(+) women without a background of cervical pathology. The effect of HAART on the control of HIV replication and of immunological status (>200 CD4) through the follow-up was associated with a reduction of SIL.

Objective. Several intratype variants of HPV16 and 18 have been identified. These variants are associated with populations from different geographic regions, and show a differential distribution among the severity of the cervical lesion, most likely due to different pathogenic potential. The objective of this study was to investigate the variant distribution of HPV16 and 18 in a Mexican population and its association with the severity of the cervical lesion and the histological lineage of cervical cancer. Methods. HPV types 16 and 18 detection was performed in 412 samples of preinvasive and invasive specimens from patients attending a Primary Health-Care Center, an Early Cervical Lesion Clinic, or a Cancer Center. Distribution of HPV variants was correlated with the cytological findings and tumor cell types using contingency tables. Statistical difference was tested with the Fisher's Exact Test or its Fisher–Freeman–Halton extension for RXC tables. Alpha value was set at the P Results. Among the 277 women included in this study without cancer, 63.5% (176 cases) had a normal cytology; from the remaining 101 women, 53.5% were LSIL (54 cases), and 46.5% HSIL (47 cases). From a total of 135 invasive carcinomas, 78.5% were squamous (106 cases); 6.6% adenocarcinoma (9 cases); 9.6% adenosquamous (ADSC) (13 cases); and 5.1% were undifferentiated carcinoma (7 cases). HPV16 E and AA-a were evenly distributed among preinvasive and invasive lesions. However, the isolate AA-c was exclusively found in cervical cancer. HPV18 Var-1(E) was almost exclusively found in invasive lesions, while the HPV18 Var-2(Af) predominated in normal or preinvasive lesions. In invasive cancer, this variant was found only in squamous tumors. Conclusions. The differential distribution of HPV16 and 18 variants in cervical lesions we found further supports experimental data on the different pathogenic potential of HPV16 and 18 variants for cervical cancer development.

Human papillomavirus type 16 (HPV-16) viral load in cervicovaginal lavage samples collected from 66 human immunodeficiency virus-seropositive women was inversely correlated with blood CD4 count ( P = 0.002). HPV-16 viral load was 81-fold higher in women with cervical smears suggestive of high-grade lesions (median, 4,425,883 copies/μg of DNA) than in women with normal smears (median, 54,576), controlling for age ( P = 0.006).

To examine the critical point at which telomerase activation occurs in the course of cervical carcinogenesis.Telomeric repeat assay protocol was used to measure telomerase activity in cell samples obtained from 155 Japanese women with various cervical conditions: normal cytology (n = 62), cervical intraepithelial neoplasia (CIN) (n = 63), and invasive squamous cell carcinoma (n = 30).Telomerase activity was detected in five (8%) women with normal cytology, in 26 (41%) patients with CIN (26% of patients with CIN I, 35% with CIN II, and 68% with CIN III), and in 29 (97%) patients with invasive carcinoma. Telomerase activation was significantly more frequent in CIN than in normal cervices (P.001), and the positive rate in CIN III was significantly higher than that in CIN I (P.01) and CIN II (P.05). Furthermore, telomerase activation was significantly more frequent in invasive carcinoma than in CIN III (P.01).Our findings suggest that telomerase activation is a relatively early event in cervical carcinogenesis and correlates well with grade of cervical lesion.