Single and multiple human papillomavirus infections in cervical abnormalities in Portuguese women

Persistent infection with high-risk (HR) human papillomavirus (HPV) types is necessary for cervical cancer development. However, little is known about the influence of multiple HPV infections on cervical lesion risk. The aim of this study was to evaluate the frequency of single and multiple HPV infections in Portuguese women, and to assess the frequency of multiple infections in cervical intraepithelial neoplasia (CIN). HPV prevalence, type-specific prevalence and extent of multiple infections were assessed in 1057 cervical samples. The Clinical Array HPV assay was used to detect 35 HPV types. According to histological diagnosis, 425 samples were normal, 375 were CIN1, and 257 were CIN2+. HPV status was studied in relation to age and lesion severity. The prevalence of HPV infection was 52.7%; 25.4%, 67.2% and 76.7% were positive for any HPV type in the normal, CIN1 and CIN2+ cases, respectively. Among HPV-positive cases, 32.0% were associated with multiple infections. Among multiple infections, 96.1% harboured HR HPV types and 38.2% HR–low risk (LR) HPV types. Overall, 33 different HPV types (18 HR and 15 LR) were detected. HR HPV types (44.1%) were significantly more prevalent than LR HPV types (8.6%). The most frequent genotype was HPV 16 (25.5%), followed by HPV 31, 53, 66, 58, and 51. Multiple infections showed a significant increase (p 0.005) according to severity of neoplasia, particularly for HR–HR HPV infections (p 0.003). No association between age and multiple HPV infections was observed (p 0.812). However, multiple HR HPV infections were more frequent in women under 30 years of age (35.3%).     

Distribution of human papillomavirus among women with abnormal cervical cytology in Kuwait

This study investigates the distribution of human papillomavirus (HPV) in women with abnormal cervical cytology in Kuwait. Two hundred and ninety‐eight (298) abnormal ThinPreps were taken from women seeking routine gynecological care and screened for HPV DNA by real‐time PCR. HPV genotyping was determined by PCR‐based sequencing. HPV DNA was detected in 152 women (51%), and 29 different HPV genotypes were detected, comprising 16 high‐risk (HR) (16, 18, 31, 33, 35, 39, 45, 51, 53, 56, 58, 59, 66, 68, 73, 97), nine low‐risk (LR) (6, 11, 54, 61, 74, 81, 90, 102, 106), and four intermediate‐risk (IR) (62, 67, 84, 87). HPV16 had the highest prevalence (24.3%), followed by HPV11 (13.8%), HPV66 (11.2%), HPV33 (9.9%), HPV53 (9.2%), HPV81 (9.2%), HPV56 (7.9%) and HPV18 (6.6%). HPV prevalence was 86, 67, and 89% in women with invasive cervical carcinoma (ICC), high‐grade squamous intraepithelial lesion (HSIL) and low‐grade squamous intraepithelial lesion (LSIL), respectively. As for age distribution, 69% of all HPVs were found in women aged 20–29 years, and the HPV incidence rate deceased with increasing age. The proportion of single infections decreased as the severity of the cytological diagnosis increased, while the proportion of multiple infections increased. This study is the first of its type in Kuwait and one of few in the Middle East. The findings are consistent with the hypothesis that HPV infection is the primary cause of cervical neoplasia. They support HPV vaccine research to prevent cervical cancer and efforts to develop HPV DNA diagnostic tests. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Characterization of human papillomavirus infection in north Taiwan

The detection of human papillomavirus (HPV) is very important for the evaluation of preventative strategies for cervical cancer. The major objective of this study was to characterize the prevalence of different genotypes of HPV in north Taiwan to contribute to the epidemiological knowledge of HPV infections. Papanicolaou (Pap) cervical smears were collected from 10,543 women aged between 14 and 87 years. The polymerase chain reaction (PCR) and DNA array hybridization techniques were used to genotype 51 different HPV strains. HPV was detected in 1,577 women, which gave an overall HPV prevalence rate of 15%. Forty‐eight different genotypes were found in these patients, which included 9.7% that were high‐risk HPV (HR‐HPV) genotypes. The most common types of HR‐HPV in patients, in descending order of frequency, were HPV 52, 16, 58, 56, 39, 51, 18, 68, 31, 33, 59, 45, and 35. HPV 52 was the most frequent type in every age group. The four most common HR‐HPV types were found in 56.6% of the patients infected with HR‐HPV. In cases that were infected with multiple HPV genotypes, 69.2% had at least one HR‐HPV genotype. The rate of infection with HR‐HPV was higher in the younger age groups than the older ones. In conclusion, 48 HPV genotypes were identified from a large study of cervical screening samples and the prevalence of HPV genotypes in different age groups was very diverse. The formulation of a public health strategy for HPV vaccination should take into account the prevalence of various HR‐HPV/LR‐HPV genotypes. J. Med. Virol. 82:1416–1423, 2010. © 2010 Wiley‐Liss, Inc.     

Prevalence and distribution of single and multiple HPV infections in cytologically abnormal cervical samples from Italian women

The prevalence of single and multiple HPV infections was assessed over a cohort of 213 women with cytological abnormalities and its association with cervical neoplasia established. Roche linear array HPV genotyping test was used to identify HPV genotypes. The most prevalent HPV genotypes in cervical cancer samples were HPV16 (61.2%), HPV52 (16.1%), HPV18 (12.9%) and HPV 31 (9.6%). Multiple HR and LR HPV infections, comprising between two and 5+ HPV types, were identified in 49.7% of samples, with a significantly lower number in severe dysplasia and cervical cancer samples (p<0.05). These results seem to indicate that detection of multiple HPV infection with HR-HPV types is not significantly better as a predictor of cervical cancer than single HR-HPV infection, though further longitudinal studies are needed to better clarify the relevance of these infections to the progression of cervical neoplasia.     

Prevalence and genotype distribution of cervical human papillomavirus infection in Macao

Population‐specific epidemiological data on human papillomavirus (HPV) infection are essential for formulating strategies to prevent cervical cancer. The age‐specific prevalence of HPV infection was determined among 1,600 women enrolled for cervical screening in Macao. A U‐shaped age‐specific prevalence curve with a first peak (prevalence rate, 10%) at 20–25 years and a second peak (13%) at 51–55 years was observed. Co‐infections with multiple types were detected in 32.5% of HPV‐positive subjects and without significant variation among different age groups (P = 0.318). The majority (84.6%) of the positive samples harbored high‐ or probable high‐risk HPV types, and these types also exhibited a similar U‐shaped age‐specific prevalence curve. In contrast, low and unknown‐risk HPV types remained at a low prevalence (1.5–2.5%) throughout the age groups between 20 and 50 years, and with a small peak (4.5%) at 51–55 years. HPV 52 was the most common type found in 26.8% of positive samples, followed by HPV 16 (15.5%), HPV 68 (11.4%), HPV 18 and HPV 58 (8.9% each), HPV 54 (8.1%), HPV 53 (7.3%), HPV 39 (6.5%), HPV 33 and HPV 66 (5.7% each). In conclusion, because of the early peak of infection, vaccination and educational campaigns in Macao should start early and target at teenagers. The presence of a second peak containing mainly high‐risk HPV types in older women indicates the need to evaluate the cover of the cervical screening programme for older women. Further study to determine the contribution of HPV 52 in high‐grade cervical neoplasia and invasive cancers in Macao is warranted. J. Med. Virol. 82:1724–1729, 2010. © 2010 Wiley‐Liss, Inc.     

High frequency of multiple HPV types in cervical specimens from Danish women

Genital human papillomavirus infection (HPV) is common and usually harmless. However, chronic cervical infection with high‐risk HPV types can cause cell changes that may eventually lead to cancer. To determine the frequency of individual HPV types among mixed infections, we examined the type distribution among cervical specimens from more than 1000 Danish women. We also examined the HPV type distribution and the frequency of single and multiple HPV types for specimens from 113 women who underwent conization and were diagnosed with cervical intraepithelial neoplasia grade II or worse (CIN2+). Using microarray technology, we found that 49% of the HPV‐positive patients were infected with multiple HPV types. Among the CIN2+ diagnosed women, this frequency was 41%. The most frequently found high‐risk HPV type was HPV‐16, which was found in 25% of the HPV‐positive cervical specimens. Among the HPV positive CIN2+ diagnosed women, 48% were HPV‐16 positive. Women younger than 30 years of age had a higher frequency of multiple infections (61%) than women older than 30 years (39%). We conclude that cervical infection with multiple HPV types is common among women in all age groups and among women with or without the diagnosis of CIN2+.     

Prevalence of human papillomavirus in women attending cervical screening in the UK and Ireland: New data from northern Ireland and a systematic review and meta‐analysis

There is substantial international variation in human papillomavirus (HPV) prevalence; this study details the first report from Northern Ireland and additionally provides a systematic review and meta‐analysis pooling the prevalence of high‐risk (HR‐HPV) subtypes among women with normal cytology in the UK and Ireland. Between February and December 2009, routine liquid based cytology (LBC) samples were collected for HPV detection (Roche Cobas® 4800 [PCR]) among unselected women attending for cervical cytology testing. Four electronic databases, including MEDLINE, were then searched from their inception till April 2011. A random effects meta‐analysis was used to calculate a pooled HR‐HPV prevalence and associated 95% confidence intervals (CI). 5,712 women, mean age 39 years (±SD 11.9 years; range 20–64 years), were included in the analysis, of which 5,068 (88.7%), 417 (7.3%) and 72 (1.3%) had normal, low, and high‐grade cytological findings, respectively. Crude HR‐HPV prevalence was 13.2% (95% CI, 12.7–13.7) among women with normal cytology and increased with cytological grade. In meta‐analysis the pooled HR‐HPV prevalence among those with normal cytology was 0.12 (95% CIs, 0.10–0.14; 21 studies) with the highest prevalence in younger women. HPV 16 and HPV 18 specific estimates were 0.03 (95% CI, 0.02–0.05) and 0.01 (95% CI, 0.01–0.02), respectively. The findings of this Northern Ireland study and meta‐analysis verify the prevalent nature of HPV infection among younger women. Reporting of the type‐specific prevalence of HPV infection is relevant for evaluating the impact of future HPV immunization initiatives, particularly against HR‐HPV types other than HPV 16 and 18. J. Med. Virol. 85:295–308, 2013. © 2012 Wiley Periodicals, Inc.     

A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings.

Two cocktails of digoxigenin-labeled human papillomavirus (HPV) type-specific oligonucleotide probes and an enzyme immunoassay (EIA) were used as a basis to developed a group-specific detection method for 14 high-risk (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) and 6 low-risk (types 6, 11, 40, 42, 43, and 44) HPVs, following a general primer GP5+/bioGP6(+)-mediated PCR. The sensitivity of this high-risk/low-risk (HR/LR) HPV PCR-EIA ranged from 10 to 200 HPV copies, depending on the HPV type. Comparison of HR/LR HPV PCR-EIA with radioactive Southern blot hybridization using a general probe on the same PCR products derived from 417 cytomorphologically abnormal cervical scrapings resulted in an overall agreement of 96% between the two methods. Complete concordance between group-specific HR/LR detection and individual typing results for both single and multiple infections indicate the strong specificity of this HR/LR HPV PCR-EIA. Multiple infections could be predicted by comparing PCR-EIA optical density values of the cocktail probes with one of the individual oligonucleotide probes. This novel HR/LR PCR-EIA allows accurate and rapid identification of high-risk and low-risk HPV types in cervical scrapings and will facilitate HPV detection in HPV mass-screening programs.     

High-risk HPV detection and concurrent HPV 16 and 18 typing with Abbott RealTime High Risk HPV test

BackgroundHigh-risk human papillomavirus (HPV) is the causative agent of cervical cancer. Among the high-risk types, infection with HPV 16 and 18 is associated with significantly higher risk of disease progression, and consequently these two types together cause approximately 70% of invasive cervical cancer worldwide. Identification of HPV 16 and HPV 18 can provide valuable information for risk stratification and clinical management of patients infected with these two types in both ASC-US triage and primary screening in women over age 30. It may also be valuable in the assessment of HPV vaccine efficacy. Abbott RealTime High Risk (HR) HPV is a recently developed test for the detection of 14 high-risk HPV types with the ability to concurrently identify HPV 16 and 18.ObjectiveTo evaluate the clinical performance of Abbott RealTime HR HPV test. Study design: Abbott RealTime HR HPV was evaluated with 253 cervical specimens obtained from patients with CIN 3 and 340 specimens from patients with cervical cancer to determine clinical sensitivity of the test and the prevalence of types 16 and 18. Additionally, 757 cervical specimens obtained from women 30 years of age or older with normal cytology in a general screening population were tested to determine high-risk HPV positivity rate.ResultsThe Abbott RealTime HR HPV test detected 97.2% (246/253) of CIN 3 specimens and 98.5% (335/340) of cancer specimens. HPV 16 was the most prevalent type in both CIN 3 (72.8%) and cancer specimens (64.5%). HPV 16 and 18 combined were detected in 78.9% of high-risk HPV positive CIN 3 and 84.8% of high-risk HPV positive cancer specimens. In specimens from women 30 years of age or older with normal cytology in a screening population, the HPV positivity rate was 6.5% (49/757).ConclusionsAbbott RealTime HR HPV is a highly sensitive test for detection of high-grade cervical disease and cancer. The HPV 16 and HPV 18 typing capability of the test offers the advantage of stratifying patients at greater risk of progression and may thus aid in better patient care and management.     

Spectrum of HPV types before and after treatment of cervical intraepithelial neoplasia grade 2 and 3

BackgroundTo monitor residual disease after treatment of high grade cervical intraepithelial neoplasia (CIN), cytology together with human papillomavirus (HPV) testing are commonly performed.ObjectivesTo analyse the spectrum of HPV types before and after treatment.Study designThis register-based study included 446 women treated for CIN2 or 3, where cytology samples had been HPV-tested before and after treatment by the use of the MGP-PCR Luminex HPV L1-DNA-assay identifying 39 HPV types, including 12 high risk (HR) HPV types.ResultsBefore and after treatment, 706 and 248 HPV isolates were detected of 36 and 34 different HPV types, respectively. Among all the HR HPV isolates, type-specific persistency was observed among 14% (76/542) after treatment, compared to 34% (31/92) of low-risk (LR) HPV isolates (p < 0.001). Among the potential high risk (PHR) HPV isolates, 8.3% (6/72) persisted. Totally, 99% (440/446) and 40% (179/446) of the women were HPV-positive before and after treatment, respectively. At least one of the 12 HR HPV types was present in 91% (404/446) and 24% (109/446) of the women before and after treatment, respectively (p < 0.0001). HR HPV types were present both before and after treatment among 23% (102/446) of the women, and 16% (71/446) manifested at least one persistent HR HPV type. The sensitivity, specificity and negative predictive value of HR HPV testing for detection of residual high grade squamous intraepithelial lesion (HSIL) was based on the first cytology after treatment, and was 91.7% (95% CI: 61.5%–99.8%), 84.1% (95% CI: 80.0%–87.7%) and 99.7% (95% CI: 98.2%–100.0%), respectively.ConclusionsAbout one out six treated women (16%) manifested at least one persistent HR HPV type, that was associated with recurrent or residual HSIL disease (odds ratio 58.1, 95% CI 7.4–457) (p = 0.0001). Testing for HR HPV demonstrated high sensitivity (92%) for residual HSIL. The higher persistency rate of LR HPV types suggests that they are more likely to be outside the treated area.     

Human Papillomavirus Prevalence and Genotype Distribution among Turkish Women with or Without Cervical Lesion

Context: Human papillomavirus (HPV) infection is the main cause of cervical cancer, but the risk is associated with the various HPV genotypes which may be found in women with or without clinical findings. Aims: We aimed to identify HPV prevalence and genotype distribution in women with or without cervical lesions admitted to Gynaecology and Obstetrics Clinics of one of the largest private hospitals in Istanbul between 2013 and 2017. Subjects and Methods: In the present study, cervical cytobrush samples collected from 2464 women with different cytological conditions, and investigated for the presence of HPV, and the different genotypes. Results were evaluated based on the HPV positivity in different cytological findings, and ages. Furthermore, distribution of high-risk (HR) and low-risk (LR) genotypes in different groups was investigated. Results: Among all participants, 1925 (78.1%) was with the normal cytological condition, 354 (14.4%) with ASC-US; 151 (6.1%) with low-grade squamous intraepithelial lesion (LSIL), and 34 (1.4%) with high-grade squamous intraepithelial lesion (HSIL). Our results showed that 649 out of 2464 patients (26.3%) were positive, and 1815 (73.7%) were negative for the presence of HPV. Among 649 positive patients, 223 (34.3%) were found positive for more than one genotype. HPV 16 was found the most common HR-HPV type in ASC-US and LSIL whereas HPV 18 was the most common in HSIL. HPV 6 was found the most common LR-HPV type in ASC-US and LSIL whereas HPV 11 was the most common in HSIL. 26.9% of women <50 years old, and 22.3% of women ≥50 years old was positive for HPV. The most common HR-HPV genotype was 16 in both groups with (19%) or without (17%) abnormal cytology. Conclusions: We concluded that HPV prevalence and genotype distribution in women with or without clinical findings is an important predictor of cervical cancer.     

comparison of two commercial assays for detection of human papillomavirus (HPV) in cervical scrape specimens: validation of the Roche AMPLICOR HPV test as a means to screen for HPV genotypes associated with a higher risk of cervical disorders

Certain high-risk (HR) human papillomavirus (HPV) types are a necessary cause for the development of cervical disorders. Women with persistent HR HPV infections have an increased risk of developing high-grade cervical lesions, compared with those who have no or low-risk HPV infections. Therefore, implementation of HPV detection into cervical screening programs might identify women at risk of cervical cancer. Several HPV detection methods with different sensitivities and specificities are available. Recently, a new PCR-based technique, the Roche AMPLICOR HPV Test, was developed. This test recognizes a group of 13 HR HPV types simultaneously. This study was undertaken to validate and compare HPV detection in 573 cervical scrape specimens by the AMPLICOR HPV Test and the INNO-LiPA HPV detection/genotyping assay (SPF10-LiPA system version 1). Human beta-globin was not detected in nine specimens, which were therefore excluded from the comparison. Eleven scrape specimens containing HPV type 53 or 66 were also excluded from the comparison because these (probably) HR HPV types cannot be detected by the AMPLICOR HPV Test. The results of HPV detection by the Roche AMPLICOR HPV Test were confirmed by INNO-LiPA HPV detection/genotyping assay in 539/553 cases, showing an absolute agreement of 97.5% with a Cohen's kappa of 0.9327, indicating almost complete similarity of the two tests. Like the INNO-LiPA HPV detection/genotyping assay, the AMPLICOR HPV Test was sensitive, specific, feasible, and easy to handle. The value of the Roche AMPLICOR HPV Test with a broad-spectrum HR HPV detection has to be determined in prospective clinical studies.     

Typing of human papillomavirus in women with cervical lesions: Prevalence and distribution of different genotypes

Human papillomavirus (HPV) are distributed widely and persistent infection with high‐risk (HR) HPV is recognized as a necessary cause of cervical cancer. The aim of this study was to evaluate the distribution of different HR‐HPV genotypes in 199 women with cervical pre‐invasive lesions undergoing conservative treatment. A Linear Array HPV Genotyping Test was used to identify individual HPV genotypes in cervical samples. It was observed that the most prevalent HPV genotypes were HPV 16 (52.6%), HPV 51 (13.5%), and HPV 31 (10.9%); HPV 18 was found in 7.3% of the patients. Stratifying the different HPV genotypes according to the severity of the cervical lesion, a strong association between the increasing severity of the histological diagnosis and the detection of more carcinogenic HR‐HPV type was found, and in all but one cervical intraepithelial neoplasia of grade 3 the presence of at least one HR‐HPV could be detected, with more than 70% of cervical intraepithelial neoplasia of grade 3 patients bearing HPV 16. Multiple infections, comprising between 2 and 6 HPV types, were found in 43% of patients; however, the presence of more than 1 HR‐HPV type was not associated with an increased risk of high grade lesions. In conclusion, this data show that HPV 16, 51, 31, 52, and 18 were the prevalent types found in patients with cervical lesion undergoing conservative treatment, with a high prevalence of HPV 16 in cervical intraepithelial neoplasia of grade 3 patients. No association between multiple infection and severity of the lesion could be found. J. Med. Virol. 81:271–277, 2009. © 2008 Wiley‐Liss, Inc.     

Genital human papillomavirus infection among women recruited for routine cervical cancer screening or for colposcopy determined by Hybrid Capture II and polymerase chain reaction.

The purpose of this study was to evaluate the clinical use of the Hybrid Capture (HC)-II system for the detection of human papillomavirus (HPV) DNA to identify women at risk of progression to high grade squamous intraepithelial lesions (HGSIL) and carcinomas by differentiating low risk (LR) HPV types (6, 11, 42, 43, 44) and high/intermediate risk (HR) HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68). Five hundred and ninety-six women were enrolled in the study. Among them, 466 attended the hospital for routine cytologic screening and 130 were referred for colposcopy because of an abnormal Pap smear. The presence of HPV DNA was tested in cervical samples collected with the Digene Cervical Sampler in Digene Specimen Transport Medium (Digene Corporation, Silver Spring, MD, U.S.A.) using the HC-II assay. Results were compared with those obtained by polymerase chain reaction (PCR) using the MY09-MY11 primers followed by several hybridizations with specific probes. The overall HPV positivity was 32.9% by HC-II and 37.8% by PCR. Among cytologically normal smears, 19.5% were positive by HC-II (14.3% HR) and 25.1% by PCR. Of the atypical squamous cells of undetermined significance samples, 52.9% were positive by HC-II (41.1% HR) and 55.9% by PCR. Of the low grade SIL, 64.5% were positive by HC-II (59.4% HR) and 68.7% by PCR. The HPV positivity rate was found identical by both techniques in high grade smears (81.6%) and squamous cervical carcinomas (100%). By using PCR as the reference method, the sensitivity of HC-II was higher among women with abnormal cytology than with normal cytology (87.3% vs. 70%). Specificity was 80.8% and 97.5%, respectively. In summary, these results indicate that the HC-II method and MY-PCR identified nearly equivalent prevalences of HPV in cervical smear specimens.     

Vaginal self-sampling is an adequate means of screening HR-HPV types in women not participating in regular cervical cancer screening

In France, about 40% of women aged 25–65 years do not participate in regular screening and thus are at high risk (HR) of cervical cancer. Human papillomavirus (HPV) vaginal self-sampling is a valuable alternative in this population. This study aimed to assess the prevalence of HR and LR (low-risk) HPV infection in 3767 women aged >35 years from mid-socioeconomic backgrounds who carried out HPV vaginal self-sampling at home. HPV vaginal self-sampling was better accepted than the Pap-test in women aged 35–69 years who were previously non-responders to individual invitation. From the 933 self-collected swabs studied (24.7%), 62 were HPV-infected (6.6%), and 73 HPV types were found. HPV 16 was the most frequently found (43.5%), followed by 53 (23.2%), 18 (12.3%), 66 (12.3%), 31 (6.8%), 33 (5.4%) and 58 (2.7%). Ten women (16.2%) were infected by multiple HR-HPV types. Median HPV 16 load was 104.000 copies/10⁶ cells and median HPV 18 load was 833 copies/10⁶ cells. Six women (9.3%) harboured LR-HPV types. The 12-month follow-up of 43 HR-HPV positive women (69.3%) revealed CIN2–3 lesions in three women (6.9%), all HPV 16 infected, and harbouring an HPV 16 load >5 log₁₀ copies/10⁶ cells. Women harbouring HR-HPV types other than HPV 16/18 were older than women harbouring HPV 16/18 types (55 years vs. 46.9 years, p 0.0008). The high frequency of HR-HPV types in women >50 years deserves further investigation to elucidate the mechanism involved (re-infection or reactivation).     

Type‐specific human papillomavirus prevalence in cervical intraepithelial neoplasia and cancer in Iran

In Iran, human papillomavirus (HPV) vaccination is not currently included in the national vaccination program and there are no comprehensive approaches to cervical screening program. Regional data on distribution of HPV types in women is important to predict the impact of current HPV vaccines. Although several studies on distribution of HPV types in cervical precancer and cancer have been conducted in Iran, in most of them HPV positive samples were subjected to specific‐primer genotyping (mainly 16 and 18), and leaving the other HPV genotypes almost undetermined. Therefore, the present study aimed to investigate the distribution of HPV types in cervical neoplasia from West and Northwest of Iran. A total of 112 women with atypia, cervical intraepithelial neoplasia, and invasive cervical cancer were included. A PCR assay was performed in all samples to detect the presence of the HPV genome using the GP5+/6+ L1 consensus primer set. All HPV positive samples were subjected for sequencing. In overall, HPV prevalence was 20% in atypica, 44.5% in cervical intraepithelial neoplasia I, 92.3% in cervical intraepithelial neoplasia II‐III, and 98.2% in invasive cervical cancer. The most frequent HPV type was HPV 16 (79.2%), which was followed by HPV types 18, 6, and 33 at the frequencies of 6.5%, 5.1%, and 2.7%, respectively. The least HPV types were found to be 31, 45, 53, 58, and 66. In conclusion, this study shows that the current HPV vaccines could have great impact to reduce the burden of cervical cancer in Iran.     

Types of Human Papillomavirus Observed in Hospital-Based Population

Background and Objectives: Human papillomavirus (HPV) is the causative agent of cervical cancer, a major cause of cancer mortality in Indian women. The current study was undertaken to add information to the existing data on HPV type distribution in Indians, in an attempt to document HPV types for future vaccination programme, if any. Materials and Methods: HPV infection was screened in 223 cervical cancer cases and 2408 healthy women without cancer and cervical intraepithelial neoplasia (control). HPV was typed using polymerase chain reaction, Southern hybridisation using specific probes and HPV GenoArray (Hybribio) test. Results: HPV DNA was found in 92.8% of cases and 7.3% of controls. Of the 383 HPV-infected women, 30.0% had single infection; 50.9% had multiple infections (two or more types) and 19.1% were infected with HPV types other than HPV-16, -18, -6 and -11. Besides HPV-16, HPV-51 and HPV-33 were also seen as single infection in cases. In cases, HPV-18 or its homologous HPV-45 was always present as co-infection with HPV-16 or with other high-risk type. Binary logistic regression (backward) analysis highlighted significant association of age, parity and socioeconomic status with HPV infection. The present study highlighted the presence of multiple HPV infection (186 of 207, 89.9%) along with HPV-16 in women with cervical cancer. In control, 27.3% were co-infected with other sexually transmitted infections, while Chlamydia trachomatis infection was seen in 13% of cases. Conclusions: The study highlighted the type of HPV infection seen among the hospital-based population. For better screening, HPV tests available in the market should include all the types seen in the population.     

Phylogenetic analysis of partial L1 gene of 10 human papillomavirus types isolated most commonly from women with normal and abnormal cervical cytology in Kuwait

This study was undertaken to evaluate the presence of human papillomavirus (HPV) variants in cervical samples. L1 genetic variable region was studied in 10 HPV types: HPV 11, 16, 18, 33, 53, 54, 56, 61, 66 and 81. A total of 116 isolates were examined, including 47 HPVs isolated from women with normal cytology and 69 with abnormal cytology of different grades. HPV sequences were detected using MY09/MY11 consensus primers. Fifty silent and 65 missense mutations were detected. Two missense mutations were detected in HPV18, 3 in HPV56 and 17 in HPV61. The number of missense mutations per isolate ranged from 1 to 3, except in HPV54 and HPV61, where 7 and 11 missense mutations were found, respectively. Most of the isolates (52.3 %) with missense mutations were isolated from women with abnormal cervical samples. Low-grade squamous intraepithelial lesion cytology diagnosis dominated all cervical abnormalities. This study is the first on the identification of molecular variants in the Middle East and suggests the circulation of new HPV subtypes and variants in Kuwait, which needs to be confirmed by further analysis of the complete HPV genome.     

Multiple human papilloma virus types in cervical infections: competition or synergy?

Mejlhede N, Pedersen BV, Frisch M, Fomsgaard A. Multiple human papilloma virus types in cervical infections: competition or synergy? APMIS 2010; 118: 346–52. Coinfection with multiple human papilloma virus (HPV) types is common in cervical HPV infection. To evaluate if infections with different HPV types occur independently, we examined 3558 women above 15 years of age suspected of cervical HPV infection. Among them, 1842 (52%) women were HPV negative and 1716 (48%) were HPV positive as analysed by a PCR‐based commercial microarray assay for mucosal types. Of the HPV‐positive samples, 824 (48%) had single infections, while 892 (52%) had multiple infections. Observed numbers of concurrent HPV types differed from expected numbers under the assumption of independence between infections by the various HPV types. Significant positive associations were observed for 16 pairs of HPV types in statistical analysis accounting for mass significance. Significant negative associations were also found, i.e. women with HPV‐16 infection had 0.4 times the odds of having HPV‐51 compared with women not infected with HPV‐16. HPV‐16 was the only type with odds ratios <1 for all pairwise combinations. While our findings of statistically significant coexistence do not prove biological dependence among HPV types, they do suggest that infections with some HPV types may depend on the existence of certain other HPV types. Any interaction between coexisting HPV types could either decrease or increase the efficacy of current HPV vaccines that offer mainly type‐specific protection, depending on whether the types vaccinated against compete with other HPV types or not.     

The prevalence of different HPV types in Turkish women with a normal Pap smear

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 25-29 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.