HPV genotype prevalence in women with abnormal pap smears in Melbourne,Australia

Carcinoma of the cervix and its precursor, high‐grade cervical intraepithelial neoplasia (CIN2/3), are associated with persistent oncogenic Human papillomavirus (HPV) infection, particularly HPV 16 and 18. HPV genotype distribution varies with severity of cervical disease, patient demographics such as age, as well as geographical location. In this study, HPV genotype prevalence was determined, using the Roche Linear Array genotyping test, among a cohort of 1,676 women being managed with ablative or excisional treatment following colposcopically directed biopsies, who were referred initially due to cytological abnormalities. HPV genotype prevalence, including presence of single and multiple infections was assessed against both histological diagnosis and age. Overall, 83.9% of women were identified as HPV positive, comprising of 32.2% single and 51.7% multiple HPV infections. Of those with an available histological diagnosis at time‐of‐treatment (n = 899), HPV positivity increased significantly with disease severity: 62.4% (normal), 77.6% (CIN1), 92.6% (CIN2), and 97.9% (≥CIN3) (P < 0.006). Similarly, a significant increase in high‐risk (HR) HPV detection was observed with severity of disease (P < 0.005). The five most prevalent genotypes were HPV 16 (35.1%), 31 (12.6%), 51 (11.1%), 52 (9.9%), and 18 (8.5%). HPV 16 was the only genotype to demonstrate a significant increase in prevalence with increasing severity of histological or cytological disease (P < 0.0001). Multiple HPV infections, including multiple HR‐HPV infections, declined significantly with age (P < 0.02). These findings provide the largest dataset of HPV genotype prevalence rates within Australian women, though are not representative of the general population. J. Med. Virol. 81:1283–1291, 2009. © 2009 Wiley‐Liss, Inc.     

Distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia and invasive cervical cancer in Canada

Infection with high‐risk human papillomavirus (HPV) causes cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC). The distribution of HPV types in cervical diseases has been previously described in small studies for Canadian women. The prevalence of 36 HPV genotypes in 873 women with CIN and 252 women with ICC was assessed on cervical exfoliated cells analyzed with the Linear Array (Roche Molecular System). HPV16 was the most common genotype in CIN and ICC. The seven most frequent genotypes in order of decreasing frequency were HPV16, 51, 52, 31, 39, 18, and 56 in women with CIN1, HPV16, 52, 31, 18, 51, 39, and 33 in women with CIN2, HPV16, 31, 18, 52, 39, 33, and 58 in women with CIN3, and HPV16, 18, 45, 33, 31, 39, and 53 in women with ICC. HPV18 was detected more frequently in adenocarcinoma than squamous cell carcinoma (P = 0.013). Adjustment for multiple type infections resulted in a lower percentage attribution in CIN of HPV types other than 16 or 18. The proportion of samples containing at least one oncogenic type was greater in CIN2 (98.4%) or CIN3 (100%) than in CIN1 (80.1%; P < 0.001 for each comparison). Multiple type infections were demonstrated in 51 (20.2%) of 252 ICC in contrast to 146 (61.3%) of 238 women with CIN3 (P < 0.001). Adjusting for multiple HPV types, HPV16 accounted for 52.1% and HPV18 for 18.1% of ICCs, for a total of 70.2%. Current HPV vaccines should protect against HPV types responsible for 70% of ICCs in Canadian women. J. Med. Virol. 83:1034–1041, 2011. © 2011 Wiley‐Liss, Inc.     

Prevalence characteristics of single and multiple HPV infections in women with cervical cancer and precancerous lesions in Beijing,China

We assessed the prevalence characteristics of single and multiple high-risk human papillomavirus (HR-HPV) infections. A total of 1783 women who underwent colposcopy and cervical biopsy for abnormal ThinPrep Cytology Test and/or HR-HPV subtype genotyping results were enrolled in the study. Among the participants, 770 were diagnosed with cervicitis, 395 with cervical intraepithelial neoplasia grade 1 (CIN1), 542 with CIN2-3, and 76 with squamous cell carcinoma (SCC), with HR-HPV infection rates of 75.8%, 85.8%, 95.9%, and 88.4%, respectively. The prevalence of total and multiple HR-HPV infections exhibited a bimodal age distribution with a peak at ≤25 years, a decline with age and a second peak at ≥55 years, whereas single HR-HPV infections exhibited one peak from 35 to 44 years. The four most dominant HPV genotypes were HPV 16 (29.5%), 52 (15.0%), 58 (14.2%), and 18 (10.4%). In total, 67.0%, 70.4%, and 82.1% of patients with CIN1, CIN2-3, and SCC, respectively, had a single HR-HPV infection, which increased significantly with the aggravation of the cervical lesion grade (P = 0.045). Patients with a single HPV 16 infection had higher incidences of CIN2+ (62.2%) than those with multiple HPV 16 infections (52.4%) (P = 0.021). Patients coinfected with HPV 16 had higher CIN2+ incidence than those with single HPV 52, 31, 33, 35, 39, 45, 51, 56, or 59 infections (P < 0.001). This study provided baseline data on the prevalence characteristics of single and multiple HR-HPV infections in women attending a gynecological outpatient clinic in Beijing.     

Prevalence and genotype distribution of human papillomavirus in women with cervical cancer or cervical intraepithelial neoplasia in Henan province,central China

To evaluate the prevalence of human papillomavirus (HPV) infection and its genotype among women with cervical lesions in Henan Province, central China. A total of 1317 cervical scrapes from patients with cervical intraepithelial neoplasia 1 (CIN1) (n = 91), CIN2/3 (n = 466), and cervical cancer (CC; n = 760) were collected from 2013 to 2018, and then tested for HPV genotypes using polymerase chain reaction followed by flow-through hybridization assay. The prevalence of HPV was 62.64% for patients with CIN1, 86.91% for patients with CIN2/3%, and 89.21% for patients with CC. In total, the HPV prevalence was 86.56%, and the most common HPV type was HPV16 (58.77%) followed by HPV58 (10.33%), 18 (7.67%), 52 (6.61%), and 33 (5.54%). In this study, the high-risk HPV cumulative attribution rate of nine-valent vaccine coverage was markedly higher than that of bivalent or quadrivalent vaccine coverage in each histopathological category or overall (P < .001). Single HPV infection was the main infection category in each histopathological diagnosis, and the total infection rate was 65.83% (867/1317; P < .001). The prevalence of HPV16 or single HPV infection increased with the severity of cervical lesions (P < .001). HPV16, 58, 18, 52, and 33 may be predominant high-risk factors for cervical lesions in Henan Province. The nine-valent prophylactic HPV vaccine is more effective than a bivalent or quadrivalent vaccine for protecting women from CC in the region.     

An analysis on the combination expression of HPV L1 capsid protein and p16INK4a in cervical lesions

Human papillomavirus (HPV) infection in cervix is the most important reason for cervical cancer, but only 2% cervical HPV infection will develop into cervical cancer. So how to identify patients at risk of progressive cervical lesions from those infected with HPV to avoid over treatment is a big issue in clinic. The aims of this study were to detect the expression of HPV L1 capsid protein and p16^INK4a in cervical lesions and to investigate the combination expression of HPV L1 capsid protein and p16^INK4a in cervical lesions and its diagnostic efficiency in clinic. Immunochemical method was used to detect the expression of HPV L1 capsid protein and p16^INK4a in 169 cases of abnormal cytology. Histopathologic test was performed to identify cervical lesions of all the cases. χ² test and spearman's rank correlation were used for statistical analysis. The diagnostic sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), accuracy, and the area under the receive operating characteristic (ROC) curve (denoted by A_Z) were calculated with SPSS 13.0. All the statistical tests were two sided at the 5% level of significance. L1 expression decreased (P < 0.001), but p16^INK4a expression increased (P < 0.001) with histopathologic diagnosis increasing. The expression rates of HPV L1 capsid protein, p16^INK4a, and L1(?)/p16(+) in cervical intraepithelial neoplasia (CIN)2, CIN3, and squamous‐cell carcinoma were statistically different from those in CIN1 (P < 0.001). The expressions of HPV L1 capsid protein, L1(+)/p16(+), L1(+)/p16(?), and L1(?)/p16(?) were negatively correlated with the severity of cervical lesions (P < 0.001), whereas the expressions of p16^INK4a and L1(?)/p16(+) were positively correlated with the severity of cervical lesions (P < 0.001). The specificity and A_Z of combining L1 with p16 ^INK4a were statistically higher than L1 or p16 ^INK4a alone (P < 0.05). L1 and p16^INK4a are useful biomarkers for the early diagnosis of cervical lesions. The combination of L1 and p16^INK4a has a higher diagnostic accuracy than L1 or p16^INK4a alone in diagnosis of cervical lesions. Diagn. Cytopathol. 2010;38:573–578. © 2009 Wiley‐Liss, Inc.     

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%).     

IgG antibodies to human papillomavirus 16, 52, 58, and 6 L1 capsids: case-control study of cervical intraepithelial neoplasia in Japan

In Japan, human papillomavirus (HPV) 16, 52, and 58 are most commonly associated with cervical intraepithelial neoplasia (CIN). By contrast, HPV6 is primarily associated with genital warts. This study was designed to evaluate the association between IgG antibody responses to common HPVs and the risk of CIN development within a Japanese population. CIN cases (n = 141) and controls (n = 109) were tested for cervical HPV DNA and serum IgG antibodies to L1 capsids of HPV16, 52, 58, and 6. Seropositivity to HPV16, 52, and 58 L1 capsids was significantly higher in CIN cases than in controls: 27%, 21%, and 31% versus 16%, 11%, and 11%, respectively (P < 0.05). HPV6 L1 seropositivity was not significantly associated with CIN lesions (P = 0.11). Presence of viral DNA for either HPV16, 52, or 58 correlated with a significant antibody response against the homologous L1 capsids but not heterologous L1 capsids. Furthermore, seropositivity to multiple types of HPV16, 52, and 58 was more strongly associated with an increased risk of CIN development than seropositivity to a single type (P for trend <0.001). These findings indicate that IgG antibodies to L1 capsids of HPV16, 52, and 58 represent an increased risk of CIN development, with antibodies to multiple types being indicative of a further increase in risk. The presence of CIN lesions in women with seropositivity to multiple types suggests that viral exposure to a given type may not be protective against infections by other types and subsequent CIN development.     

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+.     

UK population based study to predict impact of HPV vaccination

BackgroundIn 2008 a human papillomavirus (HPV) vaccination programme for cervical cancer prevention was implemented in the UK. Surveillance of vaccine uptake, impact on prevalence of HPV infection and cervical cancer incidence were identified as key measures to evaluate the intervention.ObjectiveTo determine baseline HPV prevalence in unvaccinated women and predict impact of HPV vaccination on high-grade cervical disease (CIN2+).Study designA pseudo-anonymous prospective cohort was sampled on entry to the routine cervical screening programme between March 2009 and November 2010. In total, 13,306 eligible females were identified and high-risk (hrHPV) type specific status determined. Potential impact of prophylactic vaccination on CIN2+ was calculated by applying HPV vaccine clinical trial data to the baseline HPV type-specific data.ResultsOf 13,306 samples tested, 3545 (26.6%) were confirmed positive for at least one hrHPV type and 1325 (10%) were positive for low risk HPV. HPV16 was the predominant type detected in cases positive with either single or multiple hrHPV infection(s) (5.2% and 4.7%, respectively). Based on hrHPV type-specific data, Gardasil would have prevented 33.2% HPV16/18 unrelated CIN2+ compared to 47.1% for Cervarix. This difference was not statistically significant.ConclusionPrior to the introduction of the HPV vaccine, approximately one-quarter of young women were positive for hrHPV and one-tenth positive for HPV16. Post-vaccination, we anticipate a substantial absolute risk reduction in high-grade cervical disease associated with both targeted and non-targeted hrHPV types. There is no significant difference between the two commercially available vaccines in terms of clinical impact.     

The prevalence of VAIN,CIN, and related HPV genotypes in Japanese women with abnormal cytology

Vaginal intraepithelial neoplasia (VAIN) is often found by chance. We investigated the prevalence of VAIN and related human papillomavirus (HPV) types in comparison with cervical intraepithelial neoplasia (CIN). This study enrolled 648 women who were referred to the outpatient clinic of Kanazawa Medical University Hospital for abnormal cytology from January 2009 to January 2019. HPV genotypes were determined using Genosearch-31 + 4, which can detect 35 different HPV types. Colposcopy was performed at the first visit by an experienced gynecological oncologist. Among 611 subjects with squamous cell lesions, 107 (17.5%) VAIN cases were identified, and 67 (11.0%) women had both VAIN and CIN. Ultimately, 72 VAIN1, 15 VAIN2/3, 203 CIN1, 249 CIN2/3, 32 cervical squamous cell carcinomas (SCC), and one vaginal SCC (Vag-SCC) were identified. The prevalences of VAIN1, VAIN2/3, and Vag-SCC were 35.5%, 6.0%, and 3.1% of equivalent cervical lesions, respectively. The VAIN patients were older than the CIN patients (P = .002). About half of the VAIN cases were diagnosed during the follow-up. Multiple HPV infections were found in 42.9% of the VAIN and CIN patients. HPV52, 16, 51, 53, and 56 were the most common types in VAIN, whereas HPV16, 52, 58, 51, and 31 predominated in CIN. HPV18 was rare in VAIN, HPV58 was more common in CIN than in VAIN, and HPV53 and HPV73 were more common in VAIN. In conclusion, VAIN1 was identified more frequently than we expected. Various HPV types were identified in the vagina, which is likely a reservoir for HPV.     

Distribution and viral load of eight oncogenic types of human papillomavirus (HPV) and HPV 16 integration status in cervical intraepithelial neoplasia and carcinoma.

Current human papillomavirus (HPV) DNA testing using pooled probes, although sensitive, lacks specificity in predicting the risk of high-grade cervical intraepithelial neoplasia (CIN 2/3) progression. To evaluate selected HPV genotyping, viral load, and viral integration status as potential predictive markers for CIN progression, we performed HPV genotyping in formalin-fixed, paraffin-embedded cervical tissue with cervical carcinoma (29 cases) and CINs (CIN 1, 27 cases; CIN 2, 28 cases; CIN 3, 33 cases). General HPVs were screened using consensus primers GP5+/GP6+ and PGMY09/11. HPV genotyping and viral load measurement were performed using quantitative real-time PCR for eight oncogenic HPV types (16, 18, 31, 33, 35, 45, 52, and 58). HPV 16 viral integration status was evaluated by measuring HPV 16 E2/E6 ratio. We observed that HPV DNA positivity increased in parallel with the severity of CINs and carcinoma, with 59% positivity in CIN 1, 68% in CIN 2, 76% in CIN 3, and 97% in carcinoma (P trend=0.004). The eight oncogenic HPV types were significantly associated with CIN 2/3 (81%) and carcinoma (93%) (odds ratio (OR), 15.0; 95% confidence interval (CI), 5.67-39.76; P<0.0001) compared with the unknown HPV types (OR, 2.87; 95% CI, 0.89-9.22; P=0.08). HPV 16 was the predominant oncogenic HPV type in CIN 2/3 (51%) and carcinoma (71%) and integrated significantly more frequently in carcinoma than in CIN 2/3 (P=0.004). No significant differences in viral load were observed across the disease categories. Our findings suggest that selected genotyping for the eight oncogenic HPV types might be useful in separating women with a higher risk of CIN progression from those with a minimal risk. We also conclude that the HPV 16 integration status has potential to be a marker for risk assessment of CIN progression.     

Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV‐positive women

Vaginal infections may affect susceptibility to and clearance of human papillomavirus (HPV) infection and chronic inflammation has been linked to carcinogenesis. This study aimed to evaluate the association between bacterial vaginosis (BV) and inflammatory response (IR) with the severity of cervical neoplasia in HPV‐infected women. HPV DNA was amplified using PGMY09/11 primers and genotyping was performed using a reverse line blot hybridization assay in 211 cervical samples from women submitted to excision of the transformation zone. The bacterial flora was assessed in Papanicolaou stained smears, and positivity for BV was defined as ≥20% of clue cells. Present inflammatory response was defined as ≥30 neutrophils per field at 1000× magnification. Age higher than 29 years (OR:1.91 95% CI 1.06–3.45), infections by the types 16 and/or 18 (OR:1.92 95% CI 1.06–3.47), single or multiple infections associated with types 16 and/or 18 (OR: 1.92 CI 95% 1.06–3.47), BV (OR: 3.54 95% CI 1.62–7.73) and IR (OR: 6.33 95% CI 3.06–13.07) were associated with severity of cervical neoplasia (CIN 2 or worse diagnoses), while not smoking showed a protective effect (OR: 0.51 95% CI 0.26–0.98). After controlling for confounding factors, BV(OR: 3.90 95% CI 1.64–9.29) and IR (OR: 6.43 95% CI 2.92–14.15) maintained their association with the severity of cervical neoplasia. Bacterial vaginosis and inflammatory response were independently associated with severity of cervical neoplasia in HPV‐positive women, which seems to suggest that the microenvironment would relate to the natural history of cervical neoplasia. Diagn. Cytopathol. 2016;44:80–86. © 2015 Wiley Periodicals, Inc.     

Human papillomavirus (HPV) genotyping using paired exfoliated cervicovaginal cells and paraffin-embedded tissues to highlight difficulties in attributing HPV types to specific lesions

Defining type-specific human papillomavirus (HPV) infections within cervical tissues is important for understanding the pathogenesis of cervical neoplasia and assessing the effectiveness of prophylactic vaccines with limited type-specific spectra. We compared HPV DNA-testing results from 146 matched exfoliated-cell and formalin-fixed-tissue specimens collected by cervicovaginal lavage (CVL) within 90 days of each other from women with histologically confirmed cervical intraepithelial lesions (CIN). The CVL specimens were HPV typed using a MY09/11 L1 consensus primer PCR method followed by dot blot hybridization. The tissue specimens were HPV typed using an SPF(10) line probe assay HPV detection system. Of the 146 specimen pairs with evidence of CIN in the tissue, 91.8% were positive for one or more HPV types in both the tissue and cellular specimens. Tissue sections were more likely to be HPV negative (P < 0.01). Typing directly from tissue sections resolved multiple infections detected in exfoliated cells to a single HPV type in only 46.9% of cases. Combined use of both specimen types to attribute lesions to HPV type 16 (HPV-16) and/or -18 led to 43.1% attributed to HPV-16 and/or -18 by both specimen types and 19.9% attributed to HPV-16 and/or -18 by one, but not both, specimen types. Unambiguous attribution of cervical lesions to a single, specific HPV type remains a difficult proposition. Use of multiple specimen types or the development of highly sensitive and robust in situ hybridization HPV-testing methods to evaluate the certainty of attribution of lesions to HPV types might provide insights in future efforts, including HPV vaccine trials.     

High‐risk human papillomavirus load and biomarkers in cervical intraepithelial neoplasia and cancer

The purpose of this study was to examine the implication of high‐risk human papillomavirus (HPV) load in cervical intraepithelial neoplasia (CIN) and cancer, and to detect biomarkers in cervical disease. We conducted high‐risk HPV DNA load and cervical cytology tests in 343 women, cervical tissue biopsy in 143 women, and immunohistochemistry for p16^INK4A, cyclin D1, p53, cyclooxygenase‐2, Ki‐67, GLUT1, hPygopus2, and beta‐catenin. As a result, HPV load [relative light units (RLU) value] was correlated with the histological severity of cervical disease (p < 0.05). In the ‘atypical squamous cells of undetermined significance’ cytology group, 2.385 of HPV load seemed to be the cut‐off value at which ‘benign’ or CIN I can be differentiated from ‘CIN II or more severe’ (AUC = 0.712), but not statistically significant. The relative risk (odds ratio) of p16^INK4A and GLUT1 overexpression increased gradually according to the histological severity of cervical disease. The p16^INK4A showed statistically significant odds ratios in CIN II, CIN III, and cancer; GLUT1, in CIN II and CIN III; hPygopus2, in CIN III; and beta‐catenin, in CIN III and cancer. Conclusively, HPV load, p16^INK4A, and GLUT1 can be instrumental in predicting the severity of HPV‐related cervical disease. The beta‐catenin/hPygopus2 signaling may be involved in proceeding to CIN III.     

Do neutralizing antibody responses generated by human papillomavirus infections favor a better outcome of low‐grade cervical lesions?

To determine the role of neutralizing antibody generated by human papillomavirus (HPV) infections, baseline levels of serum neutralizing antibodies directed against HPV 16 and cervical HPV DNA were determined in 242 unvaccinated women with low‐grade cervical abnormalities, who were then monitored by cytology and colposcopy every 4 months. In women infected with HPV 16 (n = 42), abnormal cytology persisted longer in those positive for HPV 16‐specific neutralizing antibodies at baseline (median time to cytological regression: 23.8 vs. 7.2 months). Progression to cervical precancer (cervical intraepithelial neoplasia grade 3) within 5 years occurred only among women carrying HPV 16‐specific neutralizing antibodies (P = 0.03, log‐rank test). In women infected with types other than HPV 16 (n = 200), detection of HPV 16‐specific neutralizing antibodies was not correlated with disease outcome. In conclusion, development of specific neutralizing antibodies following natural HPV 16 infection did not favor a better outcome of low‐grade cervical lesions induced by HPV 16 or by other types; rather, detection of neutralizing antibodies generated by current infection may reflect viral persistence and thus help identify those who are at high risk of disease progression. J. Med. Virol. 84: 1128–1134, 2012. © 2012 Wiley Periodicals, Inc.     

Cervical and oral human papillomavirus types in HIV-1 positive and negative women with cervical disease in South Africa

This study tested cervical and oral human papillomavirus (HPV) infection in HIV-1 seropositive (HIV+) and seronegative (HIV-) women to determine any association between infections at both sites and the difference in prevalence of the HPV types infecting these women. Participants were 115 women referred to a colposcopy clinic after diagnosis of abnormal cervical cytology. The women showed low grade cervical intraepithelial neoplasia (CIN1) or high grade disease (CIN2/3) or no CIN based on colposcopy and histology. Typing of HPV in cervical and oral cells was by Roche linear array and included direct sequencing on selected oral samples. Cervical HPV prevalence was 86.5% and 97.1% in HIV- and HIV+ women respectively. With the exception of HPV-45, prominent in HIV+ women, the hierarchy of predominant types were similar in HIV- and HIV+ women. HPV-16 was most prevalent in both HIV+ (41.7%) and HIV- women (38.5%) with CIN2/3. Significantly more HIV+ women had multiple cervical (>1) infections than HIV- women (36.1% vs. 88.2%, P < 0.001) and more oral HPV infections (45.5% and 25% respectively; P = 0.04). The most prevalent oral HPV types were HPV-33, -11, and -72. The majority of women did not have concordant oral and cervical HPV types, reflecting possible independence of infection at the two sites. HIV immune suppression did not impact significantly on the predominant types of cervical HPV infection (except for HPV-45). HIV+ women had more multiple HPV infections and those with severe cervical disease a similar prevalence of HIV-16 but a lower HPV-18 prevalence than HIV- women.     

High‐risk HPV types in lesions of the uterine cervix of female commercial sex workers in the Philippines

In order to prevent cervical cancer, vaccines against human papilloma virus types 16 (HPV‐16) and 18 (HPV‐18) have been implemented worldwide. However, the HPV types that cause cancer can differ according to geographical area and ethnicity. In this new era of the HPV vaccine, it is important to elucidate the prevalent HPV types in each area. Therefore, the prevalence of HPV infection and cervical abnormalities among 369 female commercial sex workers in the Philippines were examined. HPV L1 gene was amplified by polymerase chain reaction (PCR) using modified GP5+/6+ primers, and genotyping was performed by sequencing cloned PCR products. HPV DNA was detected in 211 (57.2%) women, among whom 46 HPV types were identified. HPV‐52 was most common and multiple‐type infection was observed in 44.5%. Among 56 women with abnormal cervical cytology (low‐ and high‐grade squamous intraepithelial lesions and adenocarcinoma in situ), HPV‐52 was most common (23.2%), followed by HPV‐16 (19.6%), ‐58 (10.7%), and ‐67 (10.7%). Only 27% of these women were positive for HPV‐16 and ‐18. Multivariate analysis revealed that HPV‐16, ‐39, ‐52, ‐67, and ‐82 were significantly associated with abnormal cytology. Repeated analysis of HPV‐52 single‐positive samples using the original GP5+/6+ PCR primers produced negative results in 57% of cases, suggesting that the prevalence of HPV‐52 infection may have been underestimated in previous studies, and the current vaccines may not be sufficient for preventing infection and the development of premalignant lesions of the cervix in women in the Philippines. J. Med. Virol. 81:545–551, 2009. © 2009 Wiley‐Liss, Inc.     

Prevalence and viral load of oncogenic human papillomavirus types associated with cervical carcinoma in a population of North Italy

A cross‐sectional study was carried out in a population of North Italy to determine the prevalence of eight oncogenic human papillomavirus (HPV) types most commonly found in cervical carcinoma and to study the relationship between HPV DNA loads and severity of disease. A total of 597 cervical samples obtained from patients with pathological findings (n = 472) and from women with normal cytology (n = 125) were analyzed by means of normalized Real‐time PCR assays to quantify HPV‐16, ‐18, ‐31, ‐45, and ‐33 group (including ‐33, ‐52, ‐58, ‐67); the normalization of oncogenic HPV viral load was carried out by quantitation of a single copy gene. The two most common oncogenic HPV types found were 16 and 31 (24.3% and 22.9% of pathological samples, respectively); multiple infections were demonstrated in 22% of pathological samples. Overall, the HPV total viral load was found to increase with increasing severity of associated lesions, although a stronger association was observed only for HPV‐31 and HPV‐16 (γ = 0.49 and 0.41, respectively) as compared to HPV‐18 and ‐33 group (γ = 0.19 and 0.02, respectively). However, we found that high levels of HPV‐31 or 33 group DNA could be prognostic of minor oncogenic risk for high‐grade squamous intraepithelial lesions (H‐SIL) (age adjusted odds ratio [AORs] = 1.57 and 1.26, respectively) than HPV‐16 and HPV‐18 (AORs = 30 and 8, respectively). The AORs also increased with HPV total viral load and reached a maximum of AORs = 15.7. Thus, HPV load is a type‐dependent risk marker for the development of H‐SIL. J. Med. Virol. 81:278–287, 2009. © 2008 Wiley‐Liss, Inc.     

Quantitative human papillomavirus 16 and 18 levels in incident infections and cervical lesion development

Human papillomavirus (HPV) RNA levels may be a more sensitive early indicator of predisposition to carcinogenesis than DNA levels. We evaluated whether levels of HPV‐16 and HPV‐18 DNA and messenger RNA (mRNA) in newly detected infections are associated with cervical lesion development. Female university students were recruited from 1990 to 2004. Cervical samples for HPV DNA, HPV mRNA, and Papanicolaou testing were collected tri‐annually, and women were referred for colposcopically directed biopsy when indicated. Quantitative real‐time polymerase chain reaction of L1 and E7 DNA and E7 mRNA was performed on samples from women with HPV‐16 and HPV‐18 infections that were incidently detected by consensus PCR. Adjusting for other HPV types, increasing E7 cervical HPV‐16 mRNA levels at the time of incident HPV‐16 DNA detection were associated with an increased risk of cervical intraepithelial neoplasia grade 2–3 (HR per 1 log₁₀ increase in mRNA = 6.36, 95% CI = 2.00–20.23). Increasing HPV‐16 mRNA levels were also associated with an increased risk of cervical squamous intraepithelial lesions; the risk was highest at the incident positive visit and decreased over time. Neither HPV‐16 E7 DNA levels nor HPV‐18 E7 DNA nor mRNA levels were significantly associated with cervical lesion development. Report of >1 new partner in the past 8 months (relative to no new partners) was associated with increased HPV mRNA (viral level ratio [VLR] = 10.05, 95% CI = 1.09–92.56) and increased HPV DNA (VLR = 16.80, 95% CI = 1.46–193.01). In newly detected HPV‐16 infections, increasing levels of E7 mRNA appear to be associated with an increased risk of developing cervical pre‐cancer. J. Med. Virol. 81:713–721, 2009 © 2009 Wiley‐Liss, Inc.