Prevalence Of Human Papillomavirus DNA Research Articles

Abstract 4848: Penile intraepithelial neoplasia in a multinational cohort of men: the HPV Infection in Men Study.

Abstract The human papillomavirus (HPV) is an established etiologic agent in 50% of penile cancers. While invasive penile cancer is rare in the US, the incidence is nearly 2-fold higher in Hispanics versus non-Hispanics. Recent evidence from Europe suggests that the incidence of penile cancer and its precursor lesion (penile intraepithelial neoplasia [PeIN]) may be on the rise. Little is known about the epidemiology of PeIN and the role of HPV in PeIN lesion development in healthy men. Thus, the purpose of this study was to describe the incidence of PeIN, HPV type distribution within PeIN tissue, and HPV natural history leading to PeIN diagnosis in a cohort of HIV-negative men. A total of 4,117 men ages 18-70 years living in the US, Brazil, and Mexico were enrolled in the prospective HPV Infection in Men (HIM) Study. Men were examined at baseline and every 6 months over 4 years of follow-up (median: 42 months). At each clinical visit, exfoliated cells of the external genital skin (coronal sulcus/glans penis, shaft, and scrotum) were routinely collected and tested for HPV DNA using Roche Linear Array. Visually identified, HPV-related lesions were biopsied and subjected to pathologic evaluation. The INNO-LiPA genotyping assay was used to detect HPV DNA from within biopsy tissue. Estimates of PeIN incidence included newly diagnosed lesions with person time estimated from study entry to the date of biopsy. Eleven men in the HIM Study cohort developed pathologically-confirmed, dysplastic penile lesions. Two men exhibited PIN I, 4 had PeIN II, and 4 had PeIN III; one man was diagnosed with invasive penile cancer and was excluded from further analyses. The incidence rate of PeIN was 0.08 per 100 person-years (95% CI: 0.04-0.15). The median age at PeIN diagnosis was 26 years (range: 24-42). Among 9 lesions with adequate specimens for HPV analysis, HPV DNA was detected in the tissues of all PeIN lesions. Most lesions (n=8; 89%) were infected with an oncogenic HPV type, 1 (11%) was infected with only non-oncogenic HPV types, and 4 (44%) were co-infected with multiple HPV types. HPV16 was the most common type detected (5; 56%), followed by oncogenic types HPV51 (2; 22%), HPV18 (1; 11%), and HPV39 (1; 11%), and non-oncogenic types HPV11 (3; 33%) and HPV6 (2; 22%). HPV16 was present in the normal genital skin 12 months prior to lesion detection in 60% (n=3) of men with HPV16+ PeIN, and HPV51 was present in 100% (n=1) of men 12 months prior to detection of HPV51+ PeIN. The mean time from HPV16 detection to the development of HPV16+ PeIN lesions was 16.2 months (SD: 18.9). This is the first prospective evaluation of the incidence of penile cancer precursor lesions in HIV-negative men over a broad age range. The prevalence of HPV DNA in PeIN was high, particularly for HPV16. Both HPV16 and HPV51 were found to persist at least 12 months before PeIN diagnosis. These data may be useful as baseline measurements to monitor future trends in PeIN lesions. Citation Format: Christine M. Pierce Campbell, Hui-Yi Lin, William Fulp, Martha Abrahamsen, Beibei Lu, Luisa L. Villa, Eduardo Lazcano-Ponce, Anna R. Giuliano. Penile intraepithelial neoplasia in a multinational cohort of men: the HPV Infection in Men Study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4848. doi:10.1158/1538-7445.AM2013-4848

Comparison of HPV DNA testing in cervical exfoliated cells and tissue biopsies among HIV-positive women in Kenya

HIV-positive women are infected with human papillomavirus (HPV) (especially with multiple types), and develop cervical intraepithelial neoplasia (CIN) and cervical cancer more frequently than HIV-negative women. We compared HPV DNA prevalence obtained using a GP5+/6+ PCR assay in cervical exfoliated cells to that in biopsies among 468 HIV-positive women from Nairobi, Kenya. HPV prevalence was higher in cells than biopsies and the difference was greatest in 94 women with a combination normal cytology/normal biopsy (prevalence ratio, PR = 3.7; 95% confidence interval, CI: 2.4-5.7). PR diminished with the increase in lesion severity (PR in 58 women with high-grade squamous intraepithelial lesions (HSIL)/CIN2-3 = 1.1; 95% CI: 1.0-1.2). When HPV-positive, cells contained 2.0- to 4.6-fold more multiple infections than biopsies. Complete or partial agreement between cells and biopsies in the detection of individual HPV types was found in 91% of double HPV-positive pairs. The attribution of CIN2/3 to HPV16 and/or 18 would decrease from 37.6%, when the presence of these types in either cells or biopsies was counted, to 20.2% when it was based on the presence of HPV16 and/or 18 (and no other types) in biopsies. In conclusion, testing HPV on biopsies instead of cells results in decreased detection but not elimination of multiple infections in HIV-positive women. The proportion of CIN2/3 attributable to HPV16 and/or 18 among HIV-positive women, which already appeared to be lower than that in HIV-negative, would then further decrease. The meaning of HPV detection in cells and random biopsy from HIV-positive women with no cervical abnormalities remains unclear.

Age-specific prevalence of cervical human papillomavirus infection and cytological abnormalities in women in Gauteng Province

Women accessing the public health system in Gauteng province, South Africa are largely unscreened for cervical cancer and have a high background prevalence of human immunodeficiency virus (HIV) infection. This cross-sectional study describes the age-specific prevalence of human papillomavirus (HPV) infection and cytological abnormalities among this urban and peri-urban population. Over the period March 2009 - September 2011, 1 524 women attending public sector primary healthcare clinics were invited to participate in a cervical cancer screening study. All participants were screened with conventional cytology and HPV testing undertaken using the HPV linear array genotyping kit (Roche Molecular Systems). Of 1 472 women with valid cytology results, abnormalities were detected in 17.3% (n = 255), of which 9.1% (n = 134) were high-grade squamous intraepithelial lesions, and 0.5% (n = 8) suggestive of squamous carcinoma. Of the 1,445 women with complete data, the overall and high-risk HPV DNA prevalences were 74.6% (n = 1 078) and 54.3% (n = 784), respectively. HPV type 16 and/or 18 were detected in 19.5% (n = 282) of women. Age-specific prevalence of HPV showed a plateau-shaped curve. The prevalences of HPV infection and abnormal cytology were much higher than previously reported in general populations in South Africa and elsewhere. Higher age-specific prevalence and similar plateau-like age-specific epidemiological curves have previously only been described in studies among HIV-positive women. These findings have implications for planning and development of cervical screening programmes in developing countries with largely unscreened populations with a high background prevalence of HIV.

Survey of human papillomavirus types and their vertical transmission in pregnant women

BackgroundThe prevalence, genotypes, and vertical transmission characteristics of human papillomavirus (HPV) among pregnant women from Nanjing, China was investigated.MethodsCervical cells were collected from healthy pregnant women (n = 3139; stage of gestation, 24.6 ± 2.1 weeks) for cytological evaluation and determination of HPV infection status. Exfoliated oral and genital cells were collected from neonates (<1-day-old, n = 233) whose mothers were positive for HPV DNA. We used HPV Gene Chip technology with 23 HPV genotype probes to conduct our analysis.ResultsOverall prevalence of HPV DNA among pregnant women was 13.4% (422/3139). The most frequently detected HPV genotypes were HPV-16 (29.6%, 125/422), -18 (14.7%, 62/422), and -58 (14.2%, 60/422). The rate of concordance for HPV DNA in maternal-neonatal pairs was 23.6% (55/233), with HPV type-specific concordance occurring in 26 cases. A higher prevalence of HPV DNA was apparent in female neonates compared with males (17.7 vs. 11.6%).ConclusionsThe prevalence of cervical HPV DNA in pregnant women from Nanjing was low, with vertical transmission rates slightly higher. From our findings, we concluded that there was efficient vertical transmission of three HPV genotypes, with HPV-16 the most prevalent type in pregnant women and newborn babies.

Genotype Distribution of Human Papillomaviruses in Japanese Women with Abnormal Cervical Cytology

We report the prevalence and genotype distribution of human papillomaviruses (HPVs) among Japanese women with abnormal cervical cytology using the PGMY-CHUV assay, one of PGMY-PCR-based lineblot assays that was validated and shown to be suitable for the detection of multiple HPV types in a specimen with minimum bias. Total DNA was extracted from cervical exfoliated cells collected from 326 outpatients with abnormal Pap smears. Overall, 307 specimens (94%) were HPV-positive, 30% of which contained multiple genotypes. The prevalence of HPV DNA was 83% (49/59 samples) in atypical squamous cells of undetermined significance (ASC-US); 91% (20/22 samples) in atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H); 97% (130/134 samples) in low-grade squamous intraepithelial lesion (LSIL); and 99% (85/86 samples) in high-grade squamous intraepithelial lesion (HSIL). Three most frequent HPV types detected in HSIL were HPV16 (36%), HPV52 (24%), and HPV58 (14%). Our results suggest that multiple HPV infections are more prevalent in Japanese women than previously reported, and confirm that HPV52 and 58 are more dominant in their cervical precancerous lesions when compared to those reported in Western countries.

Viral load of HPV 16/18 in esophageal squamous cell carcinoma in three ethnic groups living in Xinjiang Autonomous Region, China

To investigate the viral load of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC) patients from three ethnic groups in Xinjiang. Using Gp5+/Gp6+ consensus primers, the prevalence of HPV DNA was examined in 253 paraffin-embedded ESCC samples. The presence and viral load of HPV 16 and HPV 18 were detected in Kazakhs, Uygurs and Hans using type-specific primers by quantitative real-time PCR (qRT-PCR). Among the 253 ESCC samples, 52 cases were positive for HPV DNA, all the 52 positive cases displayed HPV 16 infection, and six of the 52 cases were co-infected by HPV 16 and 18. HPV 16-positive rate and viral load were higher in lesions, and was inversely correlated with differentiation grades. However, there was no statistic significance among different differentiation grades. Also, there were no significant difference between detection rates of HPV types, viral load and age, gender, ethnic group, and lymph node metastasis. HPV 16 and HPV 18 genotypes could simultaneously be detected in ESCC specimens in three main ethnic groups in Xinjiang. The viral load of HPV 16 is higher in the ESCC lesions, and is inversely correlated with the differentiation grades. These observations reinforce the suggestion that HPV infection may involved in ESCC carcinogenesis; however, high prevalence or viral load of HPV infection does not seem to be related with high incidence of ESCC in Kazakhs, which may be the one element among the multiple risk factors contributing to ESCC.

Comparison of Hybrid Capture II, Linear Array, and a Bead-Based Multiplex Genotyping Assay for Detection of Human Papillomavirus in Women with Negative Pap Test Results and Atypical Squamous Cells of Undetermined Significance

Many methods with different levels of analytical sensitivity and clinical specificity have been developed to detect the presence of high-risk (HR) types of the human papillomavirus (HPV) in cervical samples. The Hybrid Capture II (HC-II) assay is broadly used for primary screening. In addition, several HPV genotyping assays, based on PCR methods, display higher sensitivity than the HC-II and are also used in screening programs. We evaluated the performance of three HPV DNA tests, namely, the HC-II, the Linear Array (LA) HPV genotyping assay, and an HPV type-specific E7 PCR bead-based multiplex genotyping assay (TS-MPG) that is a laboratory-developed method for the detection of HPV, in 94 women with atypical squamous cells of undetermined significance (ASC-US) and in cytological samples from 86 women with a negative Pap test. The HPV prevalence with the TS-MPG assay was increased compared to the prevalence with the LA and HC-II assays. The HPV DNA prevalence in women with ASC-US was greater with the TS-MPG assay (46.2%) than with the LA (36.3%) and HC-II (29.7%) assays. The HPV DNA prevalence in the control group was greater with the TS-MPG assay (32.1%) than with the LA assay (10.7%). Two women with ASC-US who were HPV DNA negative by the HC-II and positive by the TS-MPG or/and LA assays had lesions that progressed to low-grade squamous intraepithelial and high-grade squamous intraepithelial lesions. This study shows that the TS-MPG assay exhibited higher analytical sensitivity than the LA and HC-II assays for the detection of HPV DNA, which reduces the potential to incorrectly identify a woman's HPV infection status.

Abstract 5488: The rate of vertical transmission of human papillomavirus from mothers to infants: Relationship between infection rate and mode of delivery

Abstract Objectives: To assess the prevalence of human papillomavirus(HPV) infection among pregnant women and to evaluate the rate of vertical transmission of HPVs to their infants. Methods: 491 pregnant women and their infants delivered at Cheil General Hospital &amp; Women's Healthcare Center were prospectively recruited for this study between February 2010 and November 2011. Cervical swabs and blood samples were collected from the women at 32-36 weeks of gestation. Neonatal buccal swabs and cord blood were taken immediately after birth. HPV positive neonates were rechecked HPV DNA at 6 months postpartum. HPV genotyping with HPV DNA chip (MyGene Co., Seoul, Korea) was used to detect the HPV of mothers and neonates. Type specific PCR was performed to see HPV DNA in the maternal and cord blood in cases of mother and infant infected same types of HPV DNA. Results: HPV DNA was positive in 16%(80/500) of mothers and 3.5%(17/491) of neonates. The rate of vertical transmission of HPV to their infant was 21.3%(17/80). HPV DNA type-specific maternal/neonate concordance was 100%. 16 HPV positive infants were delivered vaginally and 1 HPV positive infant was delivered by cesarean section with labor. There is no HPV positive infants delivered from cesarean section without labor. All HPV positive neonates were converted HPV negative at 6 months after birth. There was no viremia in maternal and cord blood in cases of mother and infant infected same type of HPV DNA. Conclusions: Prevalence of HPV DNA in neonates born from HPV positive mothers was significantly high. However, these data suggest that neonatal HPV DNA positive is not true vertical infection but contamination during vaginal delivery. Key words: Human papillomavirus, vertical transmission Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5488. doi:1538-7445.AM2012-5488

Abstract PL01-02: Human papillomavirus in the etiology and prevention of genital cancers

Abstract PL01-02: Human papillomavirus in the etiology and prevention of genital cancers

Potential overestimation of HPV vaccine impact due to unmasking of non-vaccine types: Quantification using a multi-type mathematical model

IntroductionEstimates of human papillomavirus (HPV) vaccine impact in clinical trials and modelling studies rely on DNA tests of cytology or biopsy specimens to determine the HPV type responsible for a cervical lesion. DNA of several oncogenic HPV types may be detectable in a specimen. However, only one type may be responsible for a particular cervical lesion. Misattribution of the causal HPV type for a particular abnormality may give rise to an apparent increase in disease due to non-vaccine HPV types following vaccination (“unmasking”). MethodsTo investigate the existence and magnitude of unmasking, we analysed data from residual cytology and biopsy specimens in English women aged 20–64 years old using a stochastic type-specific individual-based model of HPV infection, progression and disease. The model parameters were calibrated to data on the prevalence of HPV DNA and cytological lesion of different grades, and used to assign causal HPV types to cervical lesions. The difference between the prevalence of all disease due to non-vaccine HPV types, and disease due to non-vaccine HPV types in the absence of vaccine HPV types, was then estimated. ResultsThere could be an apparent maximum increase of 3–10% in long-term cervical cancer incidence due to non-vaccine HPV types following vaccination. ConclusionUnmasking may be an important phenomenon in HPV post-vaccination epidemiology, in the same way that has been observed following pneumococcal conjugate vaccination.

Prevalence of Human Papillomavirus in Breast Cancer: A Systematic Review

We performed a systematic review and meta-analyses to estimate the prevalence of human papillomavirus (HPV) in breast carcinoma and to explore the reasons for the ongoing controversies about this issue. A comprehensive search of the Cochrane Library, MEDLINE, CANCERLIT, LILACS, and EMBASE databases was performed for papers published from January 1990 to January 2011. The medical subject heading terms were searched for the following: breast neoplasm, breast lesions, breast cancer, and HPV or human papillomavirus. Statistical analysis was performed using REVMAN 5.0. Twenty-nine primary studies, including 2211 samples, were analyzed. Overall, HPV prevalence in patients with breast cancer was 23.0% (95% CI, 21.2%-24.8%). The prevalence of HPV ranged from 13.4% (95% CI, 10.2%-16%) in Europe to 42.9% (95% CI, 36.4%-49.4%) in North America and Australia. The prevalence of HPV in controls was 12.9%. Combinations of 9 case-control studies showed that breast cancer was associated with HPV (odds ratio, 5.9; 95% CI, 3.26-10.67). We found a high prevalence of HPV DNA in breast cancer. There is strong evidence to suggest that HPV has an important role in the development of breast cancer.

High prevalence of human papillomaviruses in fresh frozen breast cancer samples

While the etiology of breast cancer remains enigmatic, some recent reports have examined the role of human papillomavirus (HPV) in breast carcinogenesis. The purpose of this study was to determine the prevalence of HPV in breast cancer tissue using PCR analysis and sequencing. Fifty-four (54) fresh frozen breast cancers samples that were removed from a cohort of breast cancer patients were analyzed. Samples were tested for HPV using comprehensive PCR primers, and in situ hybridization was performed on paraffin embedded tissue sections. Findings were correlated with clinical and pathological characteristics. The HPV DNA prevalence in the breast cancer samples was 50% (27/54) with sequence analysis indicating all cases to be positive for HPV-18 type. While HPV patients were slightly younger, no correlation was noted for menopausal status or family history. HPV positive tumors were smaller with earlier T staging and demonstrated lesser nodal involvement compared to HPV negative cancers. In situ hybridization analyses proved negative. The high proportion of HPV positive breast cancers detected in this series using fresh frozen tissues cannot be dismissed, however the role of HPV in breast carcinogenesis remains unclear and may ultimately be ascertained by monitoring future breast cancer incidence amongst women vaccinated against high risk HPV types.

Prevalence of Genital Human Papillomavirus Among Females in the United States, the National Health and Nutrition Examination Survey, 2003–2006

Genital human papillomaviruses (HPV) include >40 sexually transmitted viruses. Most HPV infections do not progress to disease, but infection with certain types of HPV can cause cervical and other anogenital and oropharyngeal cancer, and other types of HPV are associated with anogenital warts. HPV vaccines prevent infection with HPV 16 and 18, which account for 70% of cases of cervical cancer, and HPV 6 and 11, which cause 90% of the cases of anogenital warts. Using data and self-collected cervicovaginal specimens from 4150 females, 14-59 years of age, from consecutive National Health and Nutrition Examination Surveys (2003-2006), we estimated the prevalence of type-specific HPV DNA and examined sociodemographic and sexual determinants. The overall prevalence of HPV was 42.5% in females 14-59 years of age and varied significantly by age, race or ethnicity, and number of sex partners. Individual type prevalence was less than 7%, ranging from <0.5% through 6.5%. The most common type was nononcogenic HPV 62 (found in 6.5% of subjects), followed by HPV 53 and HPV 16 (4.7%), both of which are oncogenic types. The most prevalent species was nononcogenic α3. HPV infection is common among US females, with the highest burden of infection found in young females 20-24 years of age. Monitoring trends in HPV type distribution will contribute to our understanding of the early impact of HPV vaccines.

Detection of human papillomavirus DNA in urine. A review of the literature

The detection of human papillomavirus (HPV) DNA in urine, a specimen easily obtained by a non-invasive self-sampling method, has been the subject of a considerable number of studies. This review provides an overview of 41 published studies; assesses how different methods and settings may contribute to the sometimes contradictory outcomes; and discusses the potential relevance of using urine samples in vaccine trials, disease surveillance, epidemiological studies, and specific settings of cervical cancer screening. Urine sampling, storage conditions, sample preparation, DNA extraction, and DNA amplification may all have an important impact on HPV DNA detection and the form of viral DNA that is detected. Possible trends in HPV DNA prevalence in urine could be inferred from the presence of risk factors or the diagnosis of cervical lesions. HPV DNA detection in urine is feasible and may become a useful tool but necessitates further improvement and standardization.

Prevalence of human papillomavirus in spontaneously aborted products of conception

To compare the prevalence of human papillomavirus (HPV) in placentas from women with spontaneous abortions and from control women after term delivery. Cross-sectional study. Department of Obstetrics and Pathology of Pregnancy, Medical University of Lublin (Poland). Patients whose spontaneous abortions occurred between the 6th and the 16th week of pregnancy (n=51), and women after term delivery (n=78). Polymerase chain reaction (PCR). HPV DNA prevalence rate and the fraction of HPV 16/18 infections in aborted products of conception and placentas. Patients with spontaneous abortion did not differ from the controls in terms of mean age and the fraction of primiparas. The DNA of HPV was detected in 17.7% of aborted products of conception and in 24.4% of placentas from term deliveries. The aborted products of conception and full-term placentas were positive for HPV 16/18 in 11.8 and 12.8% cases, respectively. Patients whose material was positive for HPV DNA or those with confirmed HPV 16/18 did not differ significantly from HPV-negative women in terms of mean age and the fraction of primiparas. The HPV 16/18 infection rate does not seem be higher in cases of spontaneous abortions. Nevertheless, further study of the consequences of HPV infection in pregnancy is still needed.

Human Papillomavirus in Benign Prostatic Hyperplasia and Prostatic Adenocarcinoma Patients

The aim of this study was to determine the prevalence of human papillomavirus (HPV) types in tissue and HPV antibodies in prostatic disease. Prostate tissue samples were collected from 51 patients diagnosed with adenocarcinoma and 11 with benign prostatic hyperplasia (BPH). All tissue samples were confirmed by histology. Plasma samples were available for 52 prostate patients. We investigated HPV DNA prevalence by PCR, and PCR positive samples were HPV type determined by sequencing. Prevalence of antibodies against twenty-seven HPV proteins from fourteen different HPV types was assessed in the plasma samples. The HPV DNA prevalence in the tissue samples was 14% (7/51) for prostate cancer samples and 27% (3/11) for BPHs. HPV-18 was the only type detected in tissue samples (10/62). No significant difference in HPV prevalence between the prostate cancer and BPH samples was found. HPV-positive cells were identified in eight of our thirteen prostate tissue slides (3/3 BPH and 5/10 adenocarcinoma) by in situ hybridisation, and the positive cells were found in epithelial cells and peripheral blood cells. Serology data showed no significant increase in levels of antibodies against any of the HPV-18 proteins tested for in prostatic disease patients. Antibodies against HPV-1, HPV-4, HPV-6 and HPV-11 were significantly higher in the group of males with prostatic disease. Our study did not show an association between prostatic disease and either presence of HPV DNA in samples or previous exposure of high-risk HPV.

External genital human papillomavirus prevalence and associated factors among heterosexual men on 5 continents.

We examined the baseline prevalence of penile, scrotal, and perineal/perianal human papillomavirus (HPV) in heterosexual men (HM). We also evaluated baseline characteristics of HM to assess factors associated with prevalent HPV detection. We tested serum samples from 3463 HM aged 16-24 years with 1-5 lifetime female sexual partners for antibodies to HPV 6, 11, 16, and 18. We collected baseline swab specimens for the detection of DNA of HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 from 3 areas: penile, scrotal, and perineal/perianal. Risk factors for prevalent HPV DNA detection were evaluated. The prevalence of any tested HPV type was 18.7% at the penis, 13.1% at the scrotum, 7.9% at the perineal/perianal region, and 21.0% at any site. Having >3 lifetime female sexual partners had the greatest impact on HPV prevalence: odds ratio (OR) 3.2 (95% confidence interval (CI) 2.1-4.9) for HPV 6, 11, 16, and 18; and OR 4.5 (95% CI 3.3-6.1) for all HPV types tested. HPV DNA detection was highest in Africa. Neither condom usage nor circumcision was associated with HPV DNA prevalence. Genital-HPV DNA detection is common in young, sexually active HM. We found HPV to be most prevalent in African men and least prevalent in men from the Asia-Pacific region. Increased numbers of sexual partners was an important risk factor for HPV DNA prevalence.

Low prevalence of HPV in Brazilian children with retinoblastoma

Retinoblastoma is the most frequent intra-ocular malignant tumor of the childhood, occurring in 1 of 18,000-30,000 live births. Little is known about the causes of sporadic retinoblastoma and only a few authors have investigated the etiologic role of human papillomavirus (HPV), with controversial results. Formalin-fixed, paraffin-embedded tissue blocks containing retinoblastoma were retrieved from the archives of the Department of Pathology at Hospital A C Camargo, São Paulo, Brazil. All patients were treated with enucleation (21 children had both eyes enucleated). Retinoblastoma and, when possible, normal retina of each specimen, were micro-dissected under direct light microscopic visualization by using a PixCell II Laser Capture Micro-dissection System. The DNA quality was evaluated by polymerase chain reaction (PCR) amplification of 110 base pairs fragment of the human β-globin gene using primers PCO3+/PCO4+. All globin positive specimens were analyzed by PCR for the presence of HPV DNA using consensus primers GP5+/GP6+. A total of 154 specimens were evaluated. Forty-four patients also had normal retinal specimens available for analysis of DNA HPV. The DNA HPV prevalence among all tumor specimens was 4.6% (95% CI 2.0; 8.8) (7 positive specimens/153 adequate specimens). Among normal retinal specimens, the DNA HPV prevalence was 9.1% (95% CI 2.9; 20.5) (4 positive specimens/44 specimens). There was no statistically significant difference between these rates (P = 0.318). Excluding any experimental failure, our results indicate a low prevalence of HPV DNA in retinoblastomas. We were therefore unable to conclude about the association between these oncogenic viruses and this rare pediatric neoplasm.

Seroprevalence of Antibodies against Human Papillomavirus (HPV) Types 16 and 18 in Four Continents: the International Agency for Research on Cancer HPV Prevalence Surveys

Few human papillomavirus (HPV) seroprevalence studies have been carried out in women from low-resource countries. Seroprevalence of antibodies against HPV16 and HPV18 was assessed in 7,074 women ≥15 years of age (median 44 years) from eight world areas. Serum antibodies against HPV16 and HPV18 were tested for using enzyme-linked immunosorbent assay. HPV DNA was assessed using a general primer GP5+/6+-mediated PCR. HPV16 and HPV18 seroprevalence both ranged from <1% (Hanoi, Vietnam) to >or=25% (Nigeria). Of women who were HPV16 or HPV18 DNA-positive, seropositivity for the same type was 39.8% and 23.2%, respectively. Seropositivity for either type was directly associated with markers of sexual behavior. HPV16 and/or 18 (HPV16/18)-seropositive women had an increased risk of having cytologic abnormalities only if they were also HPV DNA-positive. A high international correlation was found between HPV16/18 seroprevalence and overall HPV DNA prevalence (r = 0.81; P = 0.022). However, HPV16/18 seroprevalence was substantially higher than the corresponding DNA prevalence in all study areas (although to different extents) and, contrary to DNA, tended to increase from young to middle age, and then decline or remain fairly constant. In all study areas, the vast majority of the information on the burden of exposure to HPV16/18 derived from serology. The correlation between HPV DNA and HPV serology was not very good at an individual woman level, but high at a population level. HPV serology is a poor marker of current infection or related lesions, but it can contribute, together with DNA, in evaluating the variations in the burden of HPV infection worldwide.

High-Risk Human Papillomavirus in Esophageal Squamous Cell Carcinoma

Although most cases of esophageal squamous cell carcinoma (ESCC) in western populations have been attributed to high levels of exposure to tobacco and alcohol, infectious agents have been postulated as possible causes, particularly human papillomavirus (HPV). To explore this issue, we analyzed HPV DNA prevalence and HPV types together with lifestyle factors, in relation to tumor stage and survival in a low-incidence population. Archived tumor samples from a nationwide cohort of 222 ESCC patients were tested for the presence of HPV DNA by PCR; positive samples were sequenced to determine HPV type, and p16(INK4a) status was assessed by immunohistochemistry. Of 222 ESCC patients, 8 tested HPV positive (prevalence, 3.6%; 95% confidence interval, 1.1-6.1%), of which 6 were HPV-16 positive and 2 were HPV-35 positive. Four of the eight HPV-positive tumors overexpressed p16(INK4a). None of 55 normal esophageal tissue samples from healthy participants had any detectable HPV. Although the numbers were low, it seemed that patients with HPV-positive ESCC tumors were younger than those with HPV-negative tumors (mean age, 60.8 versus 65.3 years, P = 0.18) and had higher body mass index (BMI) throughout life (mean current BMI of 25.1 for HPV positive, 22.2 for HPV negative, P = 0.08; mean BMI at 20 years of 25.8 for HPV positive, 22.1 for HPV negative, P = 0.003). We found no difference between patients with HPV-positive and HPV-negative tumors with respect to other lifestyle factors. These findings suggest a very low prevalence of HPV DNA in human ESCC. HPV is very unlikely to be a common cause of ESCC in Australia.