Hospital-based prevalence and sensitivity of high-risk human papillomavirus in Thai urban population

Background: To study the prevalence of high-risk human papillomavirus (HPV) types 16, 18, 31 and 33 in healthy Thai women using polymerase chain reaction (PCR) technique. Material and method: Two hundred and sixty three healthy urban women in Pathumthani, Thailand were recruited. Cervical cancer screening was performed and residual specimen from Pap smears was subjected to PCR to identify the presence of HPV types 16, 18, 31 and 33. Individuals’ demographic, health-specific and sexual behavior data were also collected. Results: Colposcopic biopsy revealed cases with high-grade squamous intraepithelial lesions (HSIL) and low-grade squamous intraepithelial lesions (LSIL). HPV 16 and 18 positive results were associated with abnormal Pap smears. Genotyping gave a 6.1%, 11.8%, 12.1%, and 14.1%, prevalence for HPV types 16, 18, 31 and 33, while 25% were infected with multiple HPV types. Discussion: High-risk HPV screening, used with abnormal pathology of HSIL gives 100% sensitivity and negative predictive value. Data from patient showed not significant correlation with neither different religion level of education, marital status, age of first sexual experience nor the number of sexual partners. Thus high-risk HPV screening is a recommended procedure with excellent sensitivity for detecting HSIL.     

Retrospective study of the prevalence of high-risk human papillomaviruses among Croatian women

The infection with Human papillomavirus (HPV) is the necessary cause for cervical cancer. There are at least 15 High-Risk (HR) HPV types that are significantly associated with progression of cervical intraepithelial neoplasia to cervical cancer. Since previous studies showed that the prevalence of HPV in cervical cancers varies among different geographic regions, we wanted to investigate the prevalence of HPV types in Croatia, especially low abundant HR HPV types. By means of consensus primers directed polymerase chain reaction (PCR), we analysed cervical DNA samples of 2,136 Croatian women, mostly with abnormal cervical smears, in order to detect the presence of HPV Type-specific primers were then used to determine Low-Risk (LR) HPV types 6/11 and HR HPV types 16, 18, 31, 33, 45, 52 and 58. Out of 2,136 specimens, 1,255 (58.8%) were positive for HPV More than half of positive samples were typed (64.5%) and 35.5% still remained untyped. Multiple HPV infections were found in 10.3% of the cases. The most prevalent type, including both single and multiple infections, was HPV16 with the prevalence of 15.9%, followed by HPV types 31, 6/11, 33, 18, 52, 45 and 58 with 8.7%, 7.1%, 4.5%, 3.8%, 2.3%, 1.2% and 1.1%, respectively. The significant increase of frequency from Low-grade Squamous Intraepithelial Lesions (LSIL) to High-grade Squamous Intraepithelial Lesions (HSIL) was observed for HR HPV types 16, 18, 31 and 33 but not 45, 52 and 58. The frequency of unknown HPV types was almost the same in cervical specimens of women with LSIL and those with HSIL, 19.8% and 21.1%, respectively. The prevalence of HPV infection rate decreased significantly with patient age from 68.5% (age group 12 to 24 years) to 38.8% (age group 45 to 54 years). But, in women aged 55 or older the overall prevalence increased to 56.6%. Our results indicate that prevalence of HR HPV types in Croatia is similar to other countries. We suggest that HPV positive women in Croatia should be closely monitored by typing for HR HPV types: 16, 18, 31, 33, 45, 52 and 58.     

Prevalence of human papillomavirus among Croatian women attending regular gynecological visit

Human papillomavirus (HPV) infection has been identified as major risk factor for cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. About 40 HPV viral types are commonly found in the genital tract. Most HPV infections resolve spontaneously, while persistent infection with oncogenic types, namely HPV 16 and 18 is necessary for CIN to occur and progress to cancer. Cervical screening is presently based on the Pap smear that is designed to diagnose precancerous lesions and cervical cancer The aim of this study was to investigate the prevalence of HPV DNA and to determine HPV types distribution among 361 women attending regular gynecological visit. There were 205 women (29+/-8 years old) without determined abnormal cervical lesions and 156 women (34+/-15 years old) with abnormal Pap smear; low grade squamous intraepitehelial lesions (LSIL, n=69), high grade squamous intraepithelial lesions (HSIL, n=72) and atypical squamous cells of undetermined significance (ASCUS, n=15). HPV DNA detection and genotyping was performed by Hybrid Capture 2 assay and additionally by consensus and type-specific primers directed PCR. The overall prevalence of high-risk HPV (hrHPV) in women with abnormal Pap smears was 67.9% (106/156), of which in ASCUS 33.4% (5/15), LSIL 62.3% (43/69) and HSIL 80.6% (58/72). In HPV positive specimens, HPV 16 was found as predominant type in 60.4% cases, followed by HPV 31 (8.5%), HPV 33 (6.6%) and HPV 18 (3.7%). In the group of women without obvious cervical changes the overall hrHPV prevalence was 35.6% with HPV 16 found in 43.8% cases, followed by HPV 31 (17.8%), HPV33 (9.5%) and HPV18 (6.8%). In both study groups, women with and without cervical lesions, the prevalence of HPVof indeterminate type was 14.2% and 13.7%, respectively. Our results indicate that cervical intraepithelial lesions are largely associated with HPV type 16, followed by HPV types 31, 33, 18 and HPV of indeterminate type. Although there is a significant difference in hrHPV DNA prevalence among two groups, no significant differences between particular hrHPV types distribution were observed.     

Immunocytochemical detection of HPV high-risk type L1 capsid proteins in LSIL and HSIL as compared with detection of HPV L1 DNA

OBJECTIVE: To investigate the prevalence of HPV L1 capsid proteins in HPV-infected HSIL and LSIL. STUDY DESIGN: Cervical smears from 74 women with cytologically and histologically confirmed LSIL (n = 32) and HSIL (n = 42) were collected prospectively to detect HPV high-risk (hr) types 16, 18, 33, 35, 39, 45, 56 and 58 L1-DNA by standardized L1-consensus primer PCR (MY 09/11) and L1 capsid proteins by immunocytochemistry using monoclonal antibodies T31 (HPV16) and T16 (HPV hr) in a standardized protocol. RESULTS: In HSIL and LSIL, L1 DNA was found for HPV hr in 93% and 59% and for HPV16 in 69% and 37% of the specimens, respectively. HPV L1 capsid proteins were detected in HSIL and LSIL for HPV hr in 33% and 44% and for HPV16 in 29% and 31% of the specimens, respectively. Expression of L1 capsid proteins was significantly reduced, by 59.6% for HPV hr L1 DNA-positive HSIL (P < .01) and by 40.4% for HPV 16 L1 DNA-positive HSIL (P < .01). In HPV 16 DNA-positive and HPV hr DNA-positive LSIL, no significant reduction of corresponding L1 capsid protein expression could be demonstrated. CONCLUSION: These data suggest a disturbed viral cellular interaction in HPV 16 and HPV hr-infected HSIL, with loss of viral L1 capsid antigen. In this context there is a possible role of T31 and T16 as prognostic markers to predict the prognosis of CIN.     

Association of human papillomavirus infection and abnormal anal cytology among HIV-infected MSM in Beijing, China

Background

In the recent years, dramatic increases in HIV transmission among men who have sex with men (MSM) have been observed in China. Human papillomavirus (HPV) infection related anal cancer is more common among HIV-infected MSM as compared to the general population. However, HPV infection and anal cytology has been rarely studied in HIV-infected MSM in China.

Methods

HIV-infected MSM in Beijing, China were invited to participate in this study between January and April 2011. Anal swabs were collected for examining cytology and HPV genotypes.

Results

Ninety-five eligible participants with complete questionnaire and laboratory data were included in the analyses. Thirty six of them (37.9%) showed abnormal anal cytology as follows: atypical squamous cells of undetermined significance (ASC-US) in 19 (20.0%), atypical squamous cells but cannot exclude HSIL (ASC-H) in 1 (1.1%), low-grade squamous intraepithelial lesion (LSIL) in 15 (15.8%), and high-grade squamous intraepithelial lesion (HSIL) in 1 (1.1%). HPV6 (20.0%), HPV16 (10.9%), HPV56 (10.9%), HPV52 (9.1%) and HPV39 (9.1%) were observed most frequently among those with normal anal cytology, while different distribution was found in the ones with abnormal anal cytology as HPV6 (19.4%), HPV16 (19.4%), HPV45 (16.7%), HPV52 (16.7%) and HPV18 (11.1%). In addition, HPV16, HPV45, HPV52 and HPV18 were the most frequent high-risk types in patients with abnormal anal cytology. HPV multiplicity was found to be significantly related to the prevalence of abnormal anal cytology (p for trend = 0.04).

Conclusions

High prevalence of HPV infection and abnormal anal cytology was observed among HIV-infected MSM in China. Infection of multiple HPV types or high-risk types was found to be associated with an increased risk of abnormal anal cytology.     

Human papillomavirus genotypes among infected Thai women with different cytological findings by analysis of E1 genes

Cervical cytological data may not be sufficient for cervical cancer screening and prevention. In this project, we determined HPV genotype among infected Thai women with different cytological findings by characterization of E1 genes. Five hundred and thirty-five specimens were tested by PCR amplification of the E1 genes. HPV genotypes were determined by sequencing, comparison with the GenBank database and were analyzed in relation to different cytological findings. HPV-DNA by PCR were typed and revealed 32 different genotypes. HR-HPV (HPV16, 18 or 52) was detected in all samples with cervical cancer cytology. HPV16 was most prevalent irrespective of cervical cytology. Moreover, HPV31 and 52 were most prevalent in the HSIL and LSIL groups whereas HPV66 was found mostly in the LSIL group. The LSIL group displayed the highest variation of HPV genotypes. Moreover, HPV31 and 52 predominated in the HSIL and LSIL groups especially HPV52 which was found in cancer samples. We hoped that these data of HPV genotypes can be used as preliminary data of HPV in Thailand and can serve as basic data for future research into the HPV genotype in south-east Asia.     

Type-specific HPV prevalence in cervical cancer and high-grade lesions in Latin America and the Caribbean: systematic review and meta-analysis

Background

Cervical cancer is a major public health problem in Latin America and the Caribbean (LA&C), showing some of the highest incidence and mortality rates worldwide. Information on HPV type distribution in high-grade cervical lesions (HSIL) and invasive cervical cancer (ICC) is crucial to predict the future impact of HPV16/18 vaccines and screening programmes, and to establish an appropriate post-vaccinal virologic surveillance. The aim was to assess the prevalence of HPV types in HSIL and ICC in studies in LA&C.

Methods and Findings

We performed a systematic review, following the MOOSE guidelines for systematic reviews of observational studies, and the PRISMA statement for reporting systematic reviews and meta-analyses. Inclusion criteria were at least ten cases of HSIL/ICC, and HPV-type elicitation. The search, without language restrictions, was performed in MEDLINE, Cochrane Library, EMBASE, LILACS from inception date to December 2009, proceedings, reference lists and consulting experts. A meta-analysis was performed using arc-sine transformations to stabilize the variance of simple proportions. Seventy-nine studies from 18 countries were identified, including 2446 cases of HSIL and 5540 of ICC. Overall, 46.5% of HSIL cases harbored HPV 16 and 8.9% HPV18; in ICC, 53.2% of cases harbored HPV 16 and13.2% HPV 18. The next five most common types, in decreasing frequency, were HPV 31, 58, 33, 45, and 52.Study''s limitations comprise the cross-sectional design of most included studies and their inherent risk of bias, the lack of representativeness, and variations in the HPV type-specific sensitivity of different PCR protocols.

Conclusions

This study is the broadest summary of HPV type distribution in HSIL and ICC in LA&C to date. These data are essential for local decision makers regarding HPV screening and vaccination policies. Continued HPV surveillance would be useful, to assess the potential for changing type-specific HPV prevalence in the post-vaccination era in Latin America.     

Prevalence and typing of HPV DNA in atypical squamous cells in pregnant women

OBJECTIVE: To determine the prevalence and typing of HPV DNA in pregnant women with a diagnosis of atypical squamous cells (ASC) and to assess whether pregnancy-related changes contribute to the diagnosis of ASC. STUDY DESIGN: HPV testing was performed on residual specimens from the ThinPrep Pap test (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) in pregnant women diagnosed as ASC (study group, n = 105), low and high grade squamous intraepithelial lesion (LSIL and HSIL) (positive control, n = 33) and negative for epithelial cell abnormality (negative control, n = 20). All cases were reviewed by 2 cytopathologists to obtain consensus diagnoses using the Bethesda System 2001 criteria. The study group cases were further subcategorized into ASC of undetermined significance (ASCUS, n = 99) and ASC cannot exclude HSIL (ASC-H, n = 6). HPV testing was also performed on an ASC control group consisting of 68 consecutive ASC cases in nonpregnant women, matched by age. RESULTS: Mean patient age was 23.7 years for the study group and 25.6 years for the ASC control group. HPV DNA was detected in 88.6% of cases in the study group, including 87.9% of ASC-US and 100% of ASC-H cases. Of the HPV positive cases, 79.6%, 4.3%, 5.4% and 10.8% had high-risk, mixed high- and low-risk, low-risk and unknown HPV types, respectively. The most frequent HPV types detected were: types 52 (31.2%), 16 (15.1%), 39 (11.8%), 53 (10.8%), and 18 and 58 (9.7% each). Multiple viral types were detected in 43.0% of cases. The prevalence of HPV DNA in the positive and negative controls in pregnant women was 100% and 55%, respectively. HPV DNA was detected in 83.8% of the ASC control group. CONCLUSION: Regardless of pregnancy-related changes, the prevalence of HPV DNA in pregnant women (88.6%) was similar to that found in ASC in nonpregnant women of the same reproductive-age group (83.8%), and the high-risk types accounted for the vast majority of cases (83.9%). These findings demonstrate that pregnancy-related changes do not contribute to the diagnosis of ASC in this subset of women. Furthermore, the high HPV DNA prevalence in reproductive-age women (< 40 years) suggests that HPV testing may have limited utility in effective management of these patients.     

Prevalence of human papillomavirus infection and genotype distribution determined by the cyclic-catcher melting temperature analysis in Korean medical checkup population

Although cytology screening has reduced the incidence and mortality rate of cervical cancer significantly, its usefulness is limited to samples from the site of the lesion, resulting in its low sensitivity and unsuitability for use in medical checkups. The purpose of the present study was to evaluate the prevalence of HPV infection using genotype distribution and to analyze the correlation of the HPV DNA test results with cytological results. We also evaluated the benefits of quantitative information obtained from cyclic-catcher melting temperature analysis (CMTA) in screening for cervical cancer. We performed cyclic-CMTA using Anyplex? II HPV28 Detection in combination with cervical cytology for 2,181 subjects. The following HPV positivity types were detected using cyclic-CMTA and HPV positivity was found to increase together with the severity of the cytology results: (1) For 419 HPV positive specimens, HPV DNA was detected in 18.1% of normal specimens, 78.3% of ASCUS, and all of LSIL and HSIL; (2) high-risk HPV DNAs were detected in 63.3% of normal (N=547), 65.9% of ASCUS (N=41), 76.9% of LSIL (N=13), and 88.9% of HSIL (N=9) among total detected HPV DNA regardless multiple detection; (3) multiple HPV genotypes were detected in 4.8% of normal specimens (N=2,146), 52.2% of ASCUS (N=23), 57.1% of LSIL (N=7), and 40.0% of HSIL (N=5). In addition, a high level of viral DNA was observed using cyclic-CMTA in all specimens beyond the LSIL stage according to cytology, while only 6% of specimens with normal cytology showed a correlation with viral quantitation by cyclic-CMTA. The combination of HPV genotyping with a quantitative assay and cytology will allow for a more accurate diagnosis of cervical cancer.     

Human papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia,Brazil

This study estimated the prevalence and distribution of human papillomavirus (HPV) types among women with cervical intraepithelial neoplasia (CIN) grade III and invasive cervical cancer from Goi s (Brazil Central Region). Seventy-four cases were analyzed and consisted of 18 CIN III, 48 squamous cell carcinomas, 4 adenocarcinomas, 1 adenosquamous carcinoma and 3 undifferentiated carcinomas. HPV-DNA sequences were examined in formalin-fixed and paraffin-embedded tissues using primers from L1 region GP5+/GP6+. Polymerase chain reaction products were typed with dot blot hybridization using probes for HPV 16, 18, 31, 33, 45, 54, 6/11, 42/43/44, 51/52, 56/58. The prevalence of HPV was estimated to be 76% (56/74). HPV 16 was the most frequently found type, followed by HPV 33, 18 and 31. The prevalence of untyped HPV was 6%; 79% percent of the squamous cell carcinoma cases and 61% percent of the CIN III were positive for HPV and the prevalence rate of HPV types was the same for the total number of cases. According to other studies, HPV type 16 is the most prevalent virus in all Brazilian regions, but there is variation regarding to other types. Type 18 is the second most prevalent HPV in North, Southeast and South Brazil regions and types 31 and 33 are the second most prevalent HPV in Northeast and Central Brazil, respectively.     

Prevalence of Human Papillomavirus Genotypes among African Women with Normal Cervical Cytology and Neoplasia: A Systematic Review and Meta-Analysis

Background

Several meta-analyses confirmed the five most prevalent human papillomavirus (HPV) strains in women with and without cervical neoplastic diseases are HPV16, 18, 31, 52, and 58. HPV16/18 are the predominant oncogenic genotypes, causing approximately 70% of global cervical cancer cases. The vast majority of the women studied in previous analyses were from Europe, North America, Asia, and most recently Latin America and the Caribbean. Despite the high burden of cervical cancer morbidity and mortality in Africa, a robust meta-analysis of HPV genotype prevalence and distribution in African women is lacking.

Methods and Findings

We systematically searched 14 major databases from inception to August 2013 without language restriction, following the Meta-Analysis of Observational Studies in Epidemiology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Seventy-one studies from 23 African countries were identified after screening 1162 citations and data abstracted and study quality appraised from 195 articles. HPV type-specific prevalence and distribution was estimated from 17,273 cases of women with normal cervical cytology; 1019 women with atypical squamous cells of undetermined significance (ASCUS); 1444 women with low-grade squamous intraepithelial lesion (LSIL); 1571 women with high-grade squamous intraepithelial lesion (HSIL); and 4,067 cases of invasive cervical carcinoma (ICC). Overall prevalence of HPV16/18 were 4.4% and 2.8% of women with normal cytology, 12.0% and 4.4% with ASCUS, 14.5% and 10.0% with LSIL, 31.2% and 13.9% with HSIL, and 49.7% and 18.0% with ICC, respectively. Study limitations include the lack of adequate data from Middle and Northern African regions, and variations in the HPV type-specific sensitivity of different genotyping protocols.

Conclusions

To our knowledge, this study is the most comprehensive assessment of the overall prevalence and distribution of HPV genotypes in African women with and without different cervical neoplasias. We have established that HPV16/18 account for 67.7% of ICC cases among African women. Based on our findings, we highly recommend the administration of existing prophylactic vaccines to younger women not infected with HPV16/18 and an increase in HPV screening efforts for high-risk genotypes to prevent cervical cancer. Review registration: International Prospective Register of Systematic Reviews CRD42013006558.     

Prevalence of human papillomavirus types in women with pre-neoplastic and neoplastic cervical lesions in the Federal District of Brazil

As a contribution to the public health authorities in planning prophylactic and therapeutic vaccine strategies, we describe the prevalence of human papillomavirus (HPV) types in women presenting abnormal cytological results in Pap smear screening tests in the Federal District, Central Brazil. We studied 129 cervical scraping samples from women whose cytological tests showed either pre-neoplastic or neoplastic lesions. Amplification of HPV DNA was performed by polymerase chain reaction using consensus primers MY09 and MY11 followed by identification of isolates by restriction fragment length polymorphism. We detected HPV DNA in 62% of the samples, including HPV-16 in 43.8%, HPV-58 in 12.5%, HPV-31 in 10%, HPV-53 in 6.3%, each of HPV-18 and HPV-33 in 3.8% of the isolates. Other types (HPV-35, -52, -66, -CP8304, -6, -11, and -CP8061) were less frequent (= or < 2.5% each). The prevalence of HPV-58 was relatively higher in this population than in data in South America, but similar to results obtained in other studies in Latin America, Europe, and Eastern Asia. Case-control studies need to be carried out to establish the association between the prevalence of HPV types specially the less frequent high-risk types and cervical cancer.     

Significance of high-risk human papillomavirus detection by polymerase chain reaction in primary cervical cancer screening

The purposes of this study were to evaluate the incidence of high-risk human papillomavirus (HPV) infection by polymerase chain reaction (PCR) and to assess its diagnostic usefulness in primary cervical screening. PCR testing for HPV type 16, 18, 31 and 33 was performed on 1305 specimens obtained during routine cervical cancer screening. We analysed the concurrent cervical smears and biopsy, and correlated them with the HPV infection status. We also evaluated histologically-proven cases with ASCUS smears according to HPV infection. HPV DNA was identified in eight (0.7%) of 1144 cytologically normal patients; nine (10.5%) of 86 ASCUS; seven (25.0%) of 28 LSIL; 26 (78.8%) of 33 HSIL; and in all of three squamous cell carcinomas (SCC). HPV positivity was significantly associated with cytohistological diagnosis for HSIL of more. In addition, HPV-positive ASCUS cases were found to be associated with histological abnormality rather than HPV-negative. The results indicate that high-risk HPV testing by PCR could be a useful adjunct tool for Pap smear in primary cervical screening. The combination of Pap smear and high-risk HPV testing by PCR might reduce unnecessary colposcopy-guided biopsy of women with cytological diagnosis of ASCUS.     

Significance of HPV-58 Infection in Women Who Are HPV-Positive,Cytology-Negative and Living in a Country with a High Prevalence of HPV-58 Infection

Purpose

Cervical cytology and human papillomavirus (HPV) DNA co-testing is recommended as a screening method for detecting cervical lesions. However, for women who are HPV-positive but cytology-negative, the appropriate management and significance of HPV-58 infection remain unknown.

Methods

This study of prevalent HPV detected at baseline with a median follow-up of 3.2 years evaluated the risk factors associated with cervical abnormalities and assessed the significance of HPV-58 infection. A total of 265 women were enrolled. All high-grade squamous intraepithelial lesions (HSIL) that were detected by cytology were confirmed by histology. Histological diagnoses of cervical intraepithelial neoplasia 2/3 were classified as HSIL. Women were classified into four groups according to the HPV genotype that was detected at their first visit: HPV-58 (n = 27), HPV-16 (n = 52; 3 women had HPV-58 co-infection), ten other high risk (HR) types (n = 79), or low/undetermined risk types (n = 107).

Results

Of 265 women, 20 (7.5%) had HSIL on their follow-up examinations. There were significant differences in the cumulative incidence of HSIL between the four groups (p<0.001). The 5-year cumulative incidence rates of HSIL were 34.0% (95% CI: 17.3–59.8%) in HPV-58 positive cases, 28.0% (95% CI: 13.8–51.6) in HPV-16 positive cases, 5.5% (95% CI: 2.1–14.0%) in one of the ten other types of HR-HPV positive cases, and 0% in women with low/undetermined risk HPV. When seen in women with HR-HPV (n = 158), persistent HPV infection was a significant factor associated with the development of HSIL (hazard ratio = 15.459, 95% CI: 2.042–117.045). Women with HPV-58 had a higher risk (hazard ratio = 5.260, 95% CI: 1.538–17.987) for the development of HSIL than women with HPV-16 (hazard ratio = 3.822, 95% CI: 1.176–12.424) in comparison with women with other types of HR-HPV.

Conclusion

HPV-58 has a high association with the development of HSIL in women who are HPV-positive and cytology-negative.     

A thin-layer,liquid-based pap test for mass screening in an area of China with a high incidence of cervical carcinoma. A cross-sectional,comparative study

OBJECTIVE: To confirm the accuracy of the ThinPrep Pap Test (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) on the basis of histologic diagnosis by biopsy and the detection of human papillomavirus (HPV) DNA in mass screening. STUDY DESIGN: A total of 1,997 women residing in Xiangyuan County, Shanxi Province, P.R.C., an area with a high incidence of cervical carcinoma, were enrolled in this study. We collected exfoliative cervical samples from all subjects into a liquid buffer (Preserv-Cyt [Cytyc]) and utilized for both cytologic screening using the ThinPrep Pap Test and HPV DNA testing. Subsequent colposcopic biopsies were taken on all subjects. All the tests were performed in an independent and blinded fashion. We compared the ThinPrep Pap test with colposcopic biopsy and HPV test. RESULTS: High grade squamous intraepithelial lesions (HSIL) (CIN 2/3) were identified in 74 (3.7%) of 1,993 women adequately assessed, and there were 12 cases of squamous cell carcinoma (SCC). The false negative rate of ThinPrep cytology was 3.2% for biopsy-confirmed CIN 3 and 9.3% for CIN 2. Twenty-seven (87%) of the 31 women with biopsy-confirmed CIN 3 and 12 (100%) of 12 with biopsy-confirmed SCC had a diagnosis of either HSIL or greater abnormalities on ThinPrep cytology. In addition, the HPV DNA detection rates offered a good correlation between cytology and biopsy. CONCLUSION: The ThinPrep Pap performed extremely well in this primary screening trial. We found a good correlation between ThinPrep cytology and colposcopic biopsy on detection of HSIL and SCC; cervical specimens collected in ThinPrep liquid buffer serve as a direct test for HPV as well.     

Development of a bead-based multiplex genotyping method for diagnostic characterization of HPV infection

The accurate genotyping of human papillomavirus (HPV) is clinically important because the oncogenic potential of HPV is dependent on specific genotypes. Here, we described the development of a bead-based multiplex HPV genotyping (MPG) method which is able to detect 20 types of HPV (15 high-risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68 and 5 low-risk HPV types 6, 11, 40, 55, 70) and evaluated its accuracy with sequencing. A total of 890 clinical samples were studied. Among these samples, 484 were HPV positive and 406 were HPV negative by consensus primer (PGMY09/11) directed PCR. The genotyping of 484 HPV positive samples was carried out by the bead-based MPG method. The accuracy was 93.5% (95% CI, 91.0-96.0), 80.1% (95% CI, 72.3-87.9) for single and multiple infections, respectively, while a complete type mismatch was observed only in one sample. The MPG method indiscriminately detected dysplasia of several cytological grades including 71.8% (95% CI, 61.5-82.3) of ASCUS (atypical squamous cells of undetermined significance) and more specific for high grade lesions. For women with HSIL (high grade squamous intraepithelial lesion) and SCC diagnosis, 32 women showed a PPV (positive predictive value) of 77.3% (95% CI, 64.8-89.8). Among women >40 years of age, 22 women with histological cervical cancer lesions showed a PPV of 88% (95% CI, 75.3-100). Of the highest risk HPV types including HPV-16, 18 and 31 positive women of the same age groups, 34 women with histological cervical cancer lesions showed a PPV of 77.3% (95% CI, 65.0-89.6). Taken together, the bead-based MPG method could successfully detect high-grade lesions and high-risk HPV types with a high degree of accuracy in clinical samples.     

Seven years prevalence and distribution of high and low risk HPV genotypes in women living in the metropolitan area of Naples

BackgroundThe objective of this work was to provide an update information on HPV age/genotype distribution by retrospectively analyzing a cohort of women living in the metropolitan area of Naples.MethodsFrom January 2011 to December 2017, cervical scrape specimens from 1265 women, with abnormal cytological indication, were tested for HPV DNA. The presence and the viral genotypes were assessed by the Linear Array HPV genotyping test for the detection of 37 anogenital HPV-DNA genotypes.ResultsThe overall prevalence of HPV infections was of 44.5% (95% CI 41.77–47.24). Among HR-HPV types, HPV-16 was the most common identified genotype, followed by HPV-31, -66, -59 and -51. As concern LR-HPV, HPV-53 resulted the most prevalent. Stratifying the study population by age, the total HPV infections showed a peak in younger women aged <23 years (58.5%), with a significative decrease by age (23–29 years, 54%; ≥ 30 years, 38.2%) (p < 0.001).ConclusionWe provided an HPV epidemiological analysis, highlighting the need to implement vaccination programmes and preventative screening strategies.     

Oncogenic human papillomavirus genital infection in southern Iranian women: population-based study versus clinic-based data

ABSTRACT: BACKGROUND: Epidemiological studies on genital human papilloma viruses infection (HPVs) in general population are crucial for the implementation of health policy guidelines for developing the strategies to prevent the primary and secondary cervical cancer. In different parts of Iran, there is a lack of population-based studies to determine the prevalence of HPV in the general population. The aim of this population-based study is to compare the prevalence rate of genital HPV infection among reproductive women with our previous clinic-based data, which showed a prevalence rate of 5% in women in southern Iran. RESULTS: Using general primers for all genotypes of HPV, of 799 randomly selected women, five (0.63%, 95% CI 0.23-1.55%) tested positive for HPV DNA. Overall, seven different HPV genotypes were detected: six types (16, 18, 31, 33, 51 and 56) were carcinogenic, or "high risk genotypes" and one genotype (HPV-66) was "probably carcinogenic." CONCLUSIONS: In a population-based study, the prevalence of HPV infection among southern Iranian women was lower than that observed worldwide. However, our gynaecological clinic-based study on the prevalence of HPV infection showed results comparable with other studies in the Middle East and Persian Gulf countries. Since gynaecological clinic-based data may generally overestimate HPV prevalence, estimates of prevalence according to clinic-based data should be adjusted downward by the population-based survey estimates.     

Improved endocervical sampling and HPV viral load detection by Cervex-Brush® Combi

OBJECTIVE: Liquid-based cytology (LBC) for cervical screening is becoming increasingly used. Together with SurePath LBC, various collecting devices can be utilized, among which the Cervex-Brush is the most widely used. The new Rovers Cervex-Brush Combi combines the advantages of the Cervex-Brush with the EndoCervex-Brush increasing sampling of the endocervical canal. The objective of this study was to analyse and to compare the Cervex-Brush Combi with the Cervex-Brush for the collection of squamous and endocervical cells, human papillomavirus (HPV) typing/quantification and disease detection in SurePath LBC. METHODS: Using either the Cervex-Brush or the Cervex-Brush Combi 100 consecutive SurePath LBC samples were collected using each brush type. All 200 slides were read by the FocalPoint and screened by guided screening using slide wizards. The viral load of HPV type 16 E7, 18 E7, 31 E6, 33 L1, 33 E6, 35 E4, 39 E7, 45 E7, 51 E6, 52 L1, 52 E7, 53 E6, 56 E7, 58 L1, 58 E6, 59 E7, 66 E6 and 68 E7 was determined using a TaqMan-based real-time quantitative PCR analysis. RESULTS: The mean number of sampled squamous cells did not differ between the two brush types (54 963 versus 54 595 cells). The use of the Cervex-Brush Combi, however, resulted in a two- to threefold increase in the number of sampled endocervical cells (P < 0.00001). Using the Cervex-Brush Combi slightly more lesions were detected (three versus two low-grade squamous intraepithelial lesions), and resulted in the detection of more atypical squamous cells of undetermined significance (six versus three). In the Cervex-Brush group, 60% (3/5) of abnormal smears were positive for oncogenic HPV types, whereas 66.7% (6/9) of abnormal smears in the Cervex-Brush Combi group tested positive. The median HPV viral load for samples taken with the Cervex-Brush Combi was 0.1825 copies/cell and was significantly higher than in samples taken with the Cervex-Brush (0.0042 copies/cell) (P = 0.02). CONCLUSION: Sampling with the Cervex-Brush Combi resulted in the collection of the same amount of squamous cells, but in a two to threefold harvest of endocervical cells. This led to the detection of a higher viral load for oncogenic HPV and an increase in the number of detected abnormal smears.     

Human papillomavirus in invasive cervical cancer and cervical intraepithelial neoplasia 2 and 3 in Venezuela: A cross-sectional study

BackgroundThis study investigated the distribution of human papillomavirus (HPV) types in invasive cervical cancer (ICC), cervical intraepithelial neoplasia 2 (CIN2) and cervical intraepithelial neoplasia 3 (CIN3) in Venezuela.MethodsParaffin-embedded samples from 329 women from 29 medical centers of the 24 states of Venezuela were analyzed to determine the distribution of HPV types for ICC, CIN2, and CIN3, the prevalence of single and multiple infection, and the association of HPV types with severity of lesion, comparing CIN2 versus CIN3+ (CIN3 and ICC). The samples were analyzed with the polymerase chain reaction (PCR) followed by reverse hybridization for the identification of HPV types.ResultsHPV was identified in 95/96 ICC specimens (98.9%), in 142/149 CIN3 (95.3%) and in 78/84 CIN2 samples (92.8%). The most common types for ICC and CIN3 were: HPV16, 18, 31, and 33, and for CIN2 were HPV16, 31, 51, 52, and 18. HPV single infection was found in 82.1% of ICC cases, in 79.4% of CIN2 cases, and in 77.4% of CIN3 cases. HPV16 was identified as a single infection more frequently in women with CIN3+ than in those with CIN2 (68.6% versus 46.7%, P = 0.002), and HPV16 or HPV18 types were more prevalent in CIN3+ than in CIN2 (73.4% versus 50%, P = 0.0006).Conclusionthis is the first study of the distribution of HPV types in ICC, CIN2, and CIN3 conducted throughout the territory of Venezuela. HPV16 and HPV18 were the most frequent HPV types identified in single and multiple infections in both ICC and CIN3 groups, and are associated with severity of lesion. The knowledge of the distribution of HPV types would allow organization of an HPV-DNA-based screening test, and consideration of the implementation of prophylactic vaccination in Venezuela.