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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.

Background To explore the psychological impact of the positive HPV result on pregnant women with normal cytology. Methods The psychological distress level of HPV-positive women was compared with those of HPV-negative women before the results were notified. After the notification, the distress level of women in the HPV-positive group was assessed for the 2nd time and 3rd time before colposcopy and 2 weeks post-colposcopy. The lifestyle characteristics, knowledge of cervical cancer and screening behavior were compared between groups. Logistic regression was used to assess associations between socio-demographic, lifestyle, knowledge and risk of elevated distress level. Results No statistical difference of the distress level (as measured by PHQ-9 and GAD-7) was found between HPV-positive and -negative women. Within HPV-positive group, low distress level remained through all three time-points, regardless of HPV subtypes or colposcopy diagnoses. Half of the participants were suboptimally screened before this study conducted; 7.6% were aware of the causal relationship between HPV and cervical cancer. Post-graduate degree was associated with elevated PHQ-9 score. Conclusions HPV screening was unlikely to cause additional psychological distress among pregnant population in China.

Introduction/Background* To evaluate the consistency of the efficacy of a multi-ingredient Coriolus versicolor-based vaginal gel, Papilocare®, on high-risk HPV (HR-HPV) clearance in 7 different studies. Methodology Results of the 6 month-treatment period of Papilocare ® from 5 independent observational (3 Spanish and 2 Italian hospitals) were compared to results from a randomized, open, parallel, controlled trial (Paloma: ClinicalTrials.gov NCT04002154) and an observational, multicenter, prospective, one-cohort study (PapilOBS: ClinicalTrial.gov NCT04199260). Two prospective one-cohort (Vigo and Bari), 2 retrospective one-cohort (Coruna and Hospitalet) and 1 retrospective controlled (Roma) studies have been performed. Vigo study. Secondary endpoint (SE): HPV clearance in 25 patients infected by HPV 16 and/or 18. Bari study. Primary endpoint (PE): HPV clearance in 98 HR-HPV patients. Coruna study: PE; HPV clearance assessed in 57 medical patients’ records. Hospitalet study. PE: composite efficacy variable (patients with normal cytology and/or HPV clearance) in 91 HR-HPV patients. Roma study. PE: HPV clearance in 183 HR-HPV patients. PapilOBS study. SE: HR-HPV clearance in 178 patients. Paloma trial. SE: HR-HPV clearance in 66 patients. Result(s)* After the 6-month treatment period, 48% and 57% of patients cleared HPV 16-18 and HR-HPV in Vigo and Bari studies, respectively. 58% of reduction was observed in the number of HR-HPV patients (Coruna) and 72.5% of patients negativized cytology and/or cleared HR-HPV (Hospitalet). 67% HR-HPV clearance was observed (treated group) vs 37.2% (control group), p Conclusion* Papilocare® has shown clinically significant consistent rates of HR-HPV clearance ranging from 50% to 70% in 7 different studies and 827 patients. These results reinforce the evidence of its beneficial effect for HR-HPV patients.

Prevalence of cervical Human Papillomavirus infection and type distribution vary with different environments. Knowledge of this will help in some cervical cancer interventions such as vaccine administration. This study aimed at determining the prevalence of cervical HPV infection among women attending a tertiary hospital in Awka, Nigeria. To evaluate cervical HPV Infections, cervical samples were collected over a period of 1 year from 405 consenting women. Multiplex PCR and cytology were used in the study. Semi-structured questionnaire was used to obtain the demographic characteristics of the participants. Statistical analysis was done using IBM SPSS statistics version 21. The findings showed that of the 405 women, 387 (94.4%) had normal cytology, and 18 (4.4%) had Low-grade Squamous Intraepithelial Lesion (LSIL). There was no High-grade Squamous Intraepithelial Lesion (HSIL). HPV prevalence of (79) 19.5% was obtained overall in the 405 women, (75 of 387) 19.4% with normal cytology, (4 of 18) 22.2% with LSIL. Age specific prevalence peaked at age group 30 - 39 and a second peak at 60 - 69. HPV types obtained were HPV 16 31 (7.7%), HPV 18 24 (5.9%), HPV 35 3 (0.7%), HPV 33 9 (2.2%), HPV 68 3 (0.7%) and multiple infections (9) 2.2%. HPV 16 was the only type found in LSIL. Regular HPV typing and screening of our women for HPV infection and Pap’s smear can go a long way in the reduction of 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

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

Background: During 2013 and 2016 the Region of Skåne, Sweden, started to analyse human papillomavirus (HPV) and cytology in postmenopausal women 60-65 years of age. Our aim was to evaluate if the presence of high-risk (HR) HPV mRNA could predict the development of cervical abnormalities among HR-HPV DNA positive women with normal cytology. Methods: A total of 271 women, 60-65 years of age, underwent liquid based cytology (LBC) and HPV testing by using the HR-HPV DNA MGP-PCR-Luminex assay. HR-HPV DNA-positive women with normal cytology underwent complimentary HPV mRNA testing (Aptima, Hologic). Over a period of 49 months (SD 11.0) the women received regular follow-up at intervals of 12-18 months. Women with abnormal cytology and/or a positive HR-HPV result at two subsequent visits were scheduled for colposcopy and clinical examination. Results: Over the surveillance period, 3.6% (10/271) of the HR-HPV DNA positive women developed histologically confirmed high-grade squamous intraepithelial lesions (HSILs) or worse and 13.3% (36/271) were diagnosed with cervical atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSILs). The cumulative incidence rates (CIR) were 29.7% (CI 24.8-30.1) for HSIL or worse among HPV mRNA-positive women at enrolment (39.4% 107/271) and 0% among HPV mRNA negative women (60.5%, 164/271), (p=0.002). The corresponding CIRs for ASCUS and LSIL was 59.9% (95% CI 59.3-66.2) and 26.1% (95 %CI 16.5-35.9), (p=0.001). Conclusions : Postmenopausal women with normal cytology along with presence of HR-HPV mRNA are at increased risk for development of severe cervical dysplasia, in contrast to those women with negative HR-HPV mRNA.

Introduction/Background In general patients with ASC-US/LSIL cytology will be followed periodically with three or six month interval. We performed liquid nitrogen cryotherapy (N2Cryo) of less than thirty second duration for the purpose of clearance of abnormal cytology and persistent HPV infection. Methodology Between April 2015 to May 2019, retrospectively we analyzed patients with abnormal cytology of ASC-US/LSIL into the groups: A group of 37 cases with just follow-up without any treatment, B group of 39 cases with N2Cryo according to colposcopic and/or cytological abnormality and HPV infection. Furthermore, 26 patients with HSIL undergone N2Cryo were also compared to the effectiveness of clearance of abnormal cytology and HPV infection. Patients performed N2Cryo three times every four weeks with written informed consent. Results Among 37 patients with ASC-US/LSIL followed by no treatment, 2 cases recovered spontaneously with normal cytology (NILM) and HPV negative (complete regression: CR), 15 cases with partial regression (PR) (CR+PR Regression Rate (RR): 45.9%) including NILM or HPV negative, 6 cases with persistence, 2 cases with progressed to HSIL. However, 12 cases were missed with no visit during follow-up. Among 39 patients with ASC-US/LSIL treated by N2Cryo, 14 cases showed CR, 10 cases showed PR, with RR: 61.5%, including 8 cases with persistence. Furthermore, 26 cases with HSIL treated by N2Cryo, 8 cases showed CR, 12 cases showed PR with RR: 76.9%, and 4 cases with persistence. Conclusion Liquid nitrogen cryotherapy (N2Cryo) might be useful for the CIN regression, especially with avoidance of cone biopsy for cases with HSIL. Disclosure Nothing to disclose.

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.

Introduction: Human Papillomavirus (HPV), a small circular double stranded DNA virus is the major aetiological agent of cervical precancerous and cancerous lesions. Genital HPV types are divided into high and low risk types, according to their oncogenic potential. The proportion of women infected with HPV varies greatly across populations as is the distribution of HPV genotypes. Aim: The present pilot study was conducted to determine the most frequent genotypes of HPV associated with: a) Histologically proven cases of cervical carcinoma; b) Women with normal cervical cytology. Materials and Methods: The present hospital based crosssectional study was conducted on 132 women attending Obstetrics and Gynaecology department of a tertiary care hospital. Consecutive cervical brushings were collected from women presenting with any type of cervical lesion and were subjected to cytology, histopathological examination, HPV DNA testing and genotyping by using Sacace real time PCR. Results: Of the 132 women studied between January 2014- October 2014, 50 (37.87%) had histologically proven cervical carcinoma and 82 (62.12%) had normal cytology. In proven cases of cervical carcinoma, HPV infection was found to be associated in 49/50 (98%) and all of them had high risk HPV genotypes. The most common genotypes were 16 (67.34%) and 18 (20.4%). Other genotypes present were 45 and 33. Out of 82 cytological normal women, five showed presence of HPV DNA on RT PCR. While all the five had infection of HPV genotype 18, in one there was presence of both 16 and 18 genotypes. Conclusion: The detection of HPV genotypes 16, 18 along with high risk type 33 and 45 in Malwa region of Punjab confirm the importance of identifying the types of HPV that infects this community to design more effective prevention strategies and thus contribute to fight against cervical cancer.

Background: Although the positron emission tomography-computed tomography (PET-CT) is a useful tool for the evaluation of mediastinal and/or hilar lymphadenopathy (MHL), direct tissue sampling is necessary for the confirmation of the findings. Objectives: Our aim was to assess the added value of endobronchial ultrasound guided-transbronchial needle aspiration (EBUS-TBNA) to PET-CT for the diagnosis of MHL. Methods: We retrospectively evaluated all patients who underwent both EBUS-TBNA sampling and PET-CT from February 2016 to August 2017. PET-CT avid MHL and the cytology from EBUS-TBNA samples were analysed. Results: Over the 18-month period, 44 PET-CT were conducted; 146 patients with MHL underwent EBUS-TBNA with 136 of them having adequate lymphoid tissues (93%). The patients who underwent PET-CT and EBUS-TBNA are summarized in the table below. Nine patients, with PET-CT positive but normal cytology on EBUS-TBNA samples, underwent follow up imaging or surgical lymph node biopsy in our hospital, which proved to be true negatives. Conclusions: We observed, albeit our sample numbers, that PET-CT inavid MHL can be reasonably well predictive as being non-pathological when confirmed with EBUS-TBNA sampling.

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

Objective Knowledge regarding the prevalence and distribution of human papillomavirus (HPV) genotyping in healthy women is important in establishing strategies for cervical cancer screening and HPV vaccination. Methods A total of 18,170 women who visited a Korean Medical Institute for health check-ups were recruited retrospectively; they underwent HPV genotyping and conventional cervical cytology. An HPV DNA test was performed using the Anyplex™ II HPV 28 detection system (Seegene) or HPV Liquid Bead Microarray (Osang Healthcare). The distribution of HPV genotypes was assessed according to cervical cytology and age. Results HPV was detected in 3,037 (16.71%) of the 18,170 women enrolled, and 2,268 (12.48%) were positive for high-risk (HR) HPV. In total, HPV 53 (9.69% of all detected HPV viruses) was the most common type; HPV 58 (7.90%) and 52 (7.81%) were also common. HPV 54 (6.99%) was common in low-risk subjects. Overall and in the normal cytology group, the most common HPV genotype was HPV 53, whereas HPV 58 was more common in women who had atypical squamous cells of undetermined significance or low-grade squamous intraepithelial neoplasia cervical cytology. In addition, HPV 16 was the most common type in cases with high-grade squamous intraepithelial neoplasia (HSIL)/atypical squamous cells-cannot exclude HSIL. Among women with normal cytology, 76 of 231 (32.9%) women under 24 years of age were positive for HR HPV, whereas 84 of 852 (9.9%) women aged 55-59 years were positive. Conclusion HPV 53 was the most prevalent genotype in healthy women. Distribution of HPV genotypes varied with cervical cytology and age. Our study provides important baseline data for the recently implemented national HPV vaccination program.

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.

HPV infection is considered to be the most important etiologic factor in cervical cancer development. In this retrospective study, which included the period from 2000 to 2012, the results of two molecular techniques used in the detection of HPV infection among women of the South Backa District were analyzed. By using the technique of in situ hybridization and the rPCR method, the proportion of high-risk HPV among women with normal cytology was determined to be 19.8% and 32.7%, respectively, and among women with abnormal cytology 43.1% and 61%, respectively. Among the analyzed women, HPV type 16 was the most prevalent, followed by HPV types 31, 51 and 18. Application of molecular HPV diagnosis is valuable because it increases the sensitivity of the screening test, so that the application of both tests to detect cervical cancer is a true prevention of malignancy.

Objective: To find out the incidence of high-risk HPV infections on climacteric women within our area of influence; and to typify HPV genotypes on women with normal cytology that come to our hospitalary unit of menopausia. Material and Method: Cross-sectional study; with a random sample of 140 cases of climacteric women of ≥50 years of age, with normal Pap smears for the last 12 months. HPV determination was carried out by PCR for screening, and by hybrid capture for genotype typification. Results: The percentage of climacteric women who are carriers of oncogenic HPV and a normal Pap smear was of 11.43% (16/140 cases). The genotype found most frequently was HPV-16, followed by HPV-58, 51 and 18. Conclusions: We found a high prevalence of women who were carriers of oncogenic HPV in climacteric women with normal Pap smears (latent infections) in our health region. We consider that cervical cancer screening, either by PCR or conventional Pap smear, should not be minimized or ignored from 50 years of age onwards.

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.