Cervical cancer is the greater cause of cancer death in women in many developing countries. Persistent infection with human papilloma virus (HPV), primarily high risk types 16 and 18, is recognized as a causal and essential factor for the development of cervical cancer. We aimed to determine the distribution of high-risk HPV genotypes in archival biopsies with cervical carcinoma in patients from Mazandaran Province, Northern Iran.
A total of 98 paraffin-embedded cervical samples consisted of 63 Squamous Cell Carcinomas (SCC), 4 Adenocarcinomas, 19 Cervical Interaepithelial Neoplasia grade I (CIN-I), 4 CIN-II and 8 CIN-III diagnosed during 2009–2011, were selected to perform high risk HPV genotyping using AmpliSens(R) HPV HCR DNA genotyping kit. The prevalence of HPV infections was assessed in low and high grade cervical lesions by age.
Of the 98 cervical samples analysed by DNA PCR, 78 (79.59%) were positive for HPV DNA. HPV was detected in the 52 of SCC, 4 of Adenocarcinomas, 14 of CIN-I, 4 of CIN-II, and 4 of CIN-III for HPV. From the 78 HPV positive samples, 23 (29.5%) samples were positive for HPV type 16, 32 (41%) were positive for HPV 18, 19 (24.4%) were positive for HPV 45, and 4 (5.1%) of cervical specimens were positive for HPV 39.
This study provides valuable baseline data for future assessment of the impact of current prophylactic vaccination programs that is protective against the two most common oncogenic types of HPV found in cervical cancer, HPV-16 and HPV-18, but not against other high-risk mucosal HPVs, 39 and 45, reported in this population.
Human papillomavirus; Cervical cancer; Genotype of HPV; PCR
Infection with high risk HPV is implicated in pre-cancerous squamous intraepithelial lesions and their progression to cervical cancer. In the developed countries, infection with HPV 16 and 18 accounts for ~70% of cervical cancers, but it has been established that HPV type prevalence differs according to worldwide geographical location. In sub Saharan Africa infection with HPV is known to be augmented by HIV, which is endemic in this region. It is not yet clear, however, whether this ultimately influences progression to cervical cancer. PapillocheckTM and multiplex PCR were used to determine the range of HPV genotypes found in cervical smears and carcinomas from HIV positive and negative Kenyan women. Smear samples from HIV-positive women had a higher prevalence of: multiple HPV infections; high-risk HPVs 52, 58, 68, potential high risk 53/70, low-risk 44/55 and abnormal cytology compared to HIV-negative women. A low overall prevalence (~8%) of types 16/18 was found in all smear samples tested (n = 224) although this increased in invasive cervical carcinoma tissues to ~80% for HIV-negative and ~46% for HIV-positive women. Furthermore, HPV45 was more common in cervical carcinoma tissues from HIV-positive women.
In summary HIV infection appears to alter the spectrum of HPV types found in both cervical smears and invasive cervical carcinomas. It is hypothesised there could be a complex interplay between these viruses which could either positively or negatively influence the rate of progression to cervical cancer.
Africa; cervical smear; HIV; HPV; Invasive cervical cancer; Subtype.
HIV-infected women have a high prevalence of human papillomavirus (HPV) infection and are more likely to be infected with HPV genotypes that are considered high-risk and have the potential for progressing to cervical cancer. The currently available HPV vaccines protect against specific HPV genotypes that may not be the most important causes of dysplasia and potentially of cervical cancer in HIV-1-infected women. African women have been underrepresented in the studies of global prevalence of HPV genotypes.
We compared the HPV genotype distribution in HIV-1-infected women from Seattle, Washington, USA and Nairobi, Kenya. The reverse line blot assay and DNA sequencing on cervicovaginal lavage (CVL) specimens were carried out.
The most commonly detected HPV types among the women from Seattle were HPV 56, 66, MM8, and 81; in contrast HPV 53, 33, and 58 were the most common HPV genotypes detected in the CVL specimens from the women in the Nairobi cohort. The HPV types associated with low-grade squamous intraepithelial lesions (LSIL) were HPV 53 and HPV 56. HPV types 58, 52, and 16 were associated with high-grade squamous intraepithelial lesions (HSIL).
A better understanding of HPV genotype distribution in the most affected regions of the world is essential to planning effective vaccine strategies if we are unable to demonstrate cross-protection between HPV genotypes included in the present vaccines and those prevalent in the different populations.
HPV genotypes; HIV-infected women; Cervical dysplasia
The HPV prevalence and genotype distribution are important for the estimation of the impact of HPV-based cervical cancer screening and HPV vaccination on the incidence of diseases etiologically linked to HPVs. The HPV genotype distribution varies across different geographical regions. Therefore, we investigated the type-specific HPV prevalence in Czech women and men with anogenital diseases.
We analyzed 157 squamous cell carcinoma samples, 695 precancerous lesion samples and 64 cervical, vulvar and anal condylomata acuminate samples. HPV detection and typing were performed by PCR with GP5+/6+ primers, reverse line blot assay and sequencing.
Thirty different HPV genotypes were detected in our study, HPV 16 being the most prevalent type both in precancerous lesions (45%) and squamous cell carcinomas (59%). In benign lesions, HPV 6 (72%) was the most common type. Altogether, 61% of carcinoma samples and 43% of precancerous lesion samples contained HPV 16 and/or 18. The presence of HPV types related to the vaccinal ones (HPV 31, 45, 33, 52, 58) were detected in 16% of carcinoma samples and 18% of precancerous lesion samples. HPV 16 and/or 18 were present in 76% of cervical cancer samples, 33% of CIN1, 43% CIN2 and 71% of CIN3 samples. HPV types 6 and/or 11 were detected in 84% samples of condylomata acuminate samples.
The prevalence of vaccinal and related HPV types in patients with HPV-associated diseases in the Czech Republic is very high. We may assume that the implementation of routine vaccination against HPV would greatly reduce the burden of HPV-associated diseases in the Czech Republic.
Cervical cancer is an important health problem in women living in developing countries. Infection with some genotypes of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer. Little information exists about HPV genotype distribution in rural and suburban regions of Mexico. Thus, we determined the prevalence of HPV genotypes in women from Tlaxcala, one of the poorest states in central Mexico, and we evaluated age infection prevalence and risk factors associated with cervical neoplasm. A cross-sectional study was conducted in 236 women seeking gynecological care at the Mexican Institute for Social Security in Tlaxcala, Mexico. Cervical scrapings were diagnosed as normal, low-grade, and high-grade squamous intraepithelial lesions (LGSIL, HGSIL). Parallel samples were used to detect HPV genotypes by PCR assays using type-specific primers for HPV 6, 11, 16, 18, and 31. An epidemiological questionnaire was applied. Prevalence of HPV infection was 31.3%. From the infected samples, prevalence of HPV 16 was 45.9%; HPV 18, 31.1%; HPV 31, 16.2%; HPV 6, 10.8%; HPV 11, 6.7%. With regard to age, the highest HPV prevalence (43.5%) was found in the 18- to 24-year-old group and the lowest (19%) in the 45- to 54-year-old group. None of the risk factors showed association with cervical neoplasia grade. HPV 16 was the most common in cervical lesions. HPV was present in 22% of normal samples and, of these, 82.6% represented high-risk HPVs. Tlaxcala showed HPV prevalence comparable to that of the largest cities in Mexico, with higher prevalence for HPV 31.
Epidemiology; Human papillomavirus; Mexico; PCR; Squamous intraepithelial lesions
The development of cervical cancer is associated with high-risk Human papilloma viruses (HPV-HR). In sub-Saharan Africa cervical cancer is the most common cancer among women and the leading cause of death attributed to malignant tumors. This study aims to identify HPV genotypes within the 30′S and 50′S HPV families found in two previous studies from our laboratory, and to determine the prevalence of twelve HPV-HR genotypes in a population of women in Ouagadougou. The twelve HPV-HR genotypes were determined by real-time multiplex PCR, in 180 samples from the general population and among a group of HIV-1 infected women.
The most common genotypes found were HPV-35 (29.4%) and HPV-31 (26.1%) of the 30′S family, and HPV-52 (29.4%) and HPV-58 (20.6%) of the 50′S family. Multiple infections of HPV-HR were observed in 78.03% of infected women.
The frequencies of HPV genotypes from the 30′S and 50′S families were higher, while the genotypes HPV-16 and18 were lower among the women in our study.
Human papillomavirus (HPV) infection causes cervical cancer and premalignant lesions of the cervix. Prevalence of HPV infection and HPV genotypes vary among different regions. However there is no data on the prevalence of HPV infection and HPV genotypes from southwest China. This study was undertaken to determine the prevalence of and risk factors for HR-HPV infection in Qujing of Yunnan province, southwest China to provide comprehensive baseline data for future screening strategies.
A sample of 5936 women was chosen by the multi-stage stratified cluster sampling method with selection probabilities proportional to size (PPS). An epidemiological questionnaire was conducted via a face-to-face interview and cervical specimens were taken for HPV DNA testing by Digene Hybrid Capture 2 (HC2) test. HPV Genotyping Reverse Hybridization Test was used for HPV genotyping. Proportions were compared by Chi-squared tests, and logistic regression was utilized to evaluate risk factors.
The median age was 38 years and the inter-quartile range was from 31 years to 47 years. 97.3% of the study population was Han nationality. Overall prevalence of HR-HPV infection was 8.3% (494/5936) and bimodal age distribution of HPV infection was observed. The five most prevalent HR-HPV genotypes were HPV-16(3.4%), HPV-56(1.7%), HPV-58(1.4%), HPV-33(1.2%) and HPV-52(0.88%). Multiple HPV infections were identified in 50.5% (208/412) of the positive genotyping specimens. Multivariate logistic regression model indicated that parity (OR = 1.35, 95% CI: 1.18-1.53, p < 0.0001) was a risk factor for HR-HPV infection, and age of 50–65 years (OR = 0.60, 95% CI: 0.45-0.80, p = 0.0005), being married or in stable relationship (OR = 0.55, 95% CI: 0.31-0.96, p = 0.035) were protective factors.
This study provided baseline data on HR-HPV prevalence in the general female population in Qujing of Yunnan province, southwest China. The finding of multiple HPV infections and bimodal age distribution revealed that HPV screening is necessary for perimenopausal women in future.
Human papillomavirus; Genotype; Cervix; Epidemiology; China
The two currently licensed human papillomavirus (HPV) vaccines are highly efficacious in preventing cervical pre-cancers related to HPV 6, 11, 16 and 18. Before implementing a large-scale HPV vaccine campaign in Viet Nam, information about the prevalence of infection with the HPV vaccine types is required. This study was done in Can Tho, the province with the highest prevalence of cervical cancer in the south of Viet Nam, to explore the distribution of other high-risk types of HPV among married women in this province.
The study employed a cross-sectional design with multistage sampling. A total of 1000 participants were randomly selected, interviewed and given gynaecological examinations. HPV infection status and HPV genotyping test were completed for all participants.
A broad spectrum of HPV types was reported in this study. The prevalence of cases infected with HPV 16 and/or 18 was 7%; the prevalence of cases infected with other high-risk HPV types was 6%. The highest prevalence for single and multiple infections, as well as for high-risk infections, was reported for the youngest age group (less than 30 years).
While it is relevant to implement an HPV vaccine campaign in Viet Nam due to the high prevalence of infection with HPV 16 and/or 18, it is important to note that one can be infected with multiple types of HPV. Vaccination does not protect against all types of high-risk HPV. Future vaccine campaigns should openly disclose this information to women receiving vaccines.
Two clinically relevant high-risk HPV (HR-HPV) types 16 and 18 are etiologically associated with the development of cervical carcinoma and are also reported to be present in many other carcinomas in extra-genital organ sites. Presence of HPV has been reported in breast carcinoma which is the second most common cancer in India and is showing a fast rising trend in urban population. The two early genes E6 and E7 of HPV type 16 have been shown to immortalize breast epithelial cells in vitro, but the role of HPV infection in breast carcinogenesis is highly controversial. Present study has therefore been undertaken to analyze the prevalence of HPV infection in both breast cancer tissues and blood samples from a large number of Indian women with breast cancer from different geographic regions.
The presence of all mucosal HPVs and the most common high-risk HPV types 16 and 18 DNA was detected by two different PCR methods - (i) conventional PCR assays using consensus primers (MY09/11, or GP5+/GP6+) or HPV16 E6/E7 primers and (ii) highly sensitive Real-Time PCR. A total of 228 biopsies and corresponding 142 blood samples collected prospectively from 252 patients from four different regions of India with significant socio-cultural, ethnic and demographic variations were tested.
All biopsies and blood samples of breast cancer patients tested by PCR methods did not show positivity for HPV DNA sequences in conventional PCRs either by MY09/11 or by GP5+/GP6+/HPV16 E6/E7 primers. Further testing of these samples by real time PCR also failed to detect HPV DNA sequences.
Lack of detection of HPV DNA either in the tumor or in the blood DNA of breast cancer patients by both conventional and real time PCR does not support a role of genital HPV in the pathogenesis of breast cancer in Indian women.
Cervical cancer is the second most common cancer in women worldwide. Infection with certain human papillomavirus (HPV) genotypes is the most important risk factor associated with cervical cancer. This study analysed the distribution of type-specific HPV infection among women with normal and abnormal cytology, to assess the potential benefit of prophylaxis with anti-HPV vaccines.
Cervical samples of 2,461 women (median age 34 years; range 15-75) from the centre of Spain were tested for HPV DNA. These included 1,656 samples with normal cytology (NC), 336 with atypical squamous cells of undetermined significance (ASCUS), 387 low-grade squamous intraepithelial lesions (LSILs), and 82 high-grade squamous intraepithelial lesions (HSILs). HPV detection and genotyping were performed by PCR using 5'-biotinylated MY09/11 consensus primers, and reverse dot blot hybridisation.
HPV infection was detected in 1,062 women (43.2%). Out of these, 334 (31%) samples had normal cytology and 728 (69%) showed some cytological abnormality: 284 (27%) ASCUS, 365 (34%) LSILs, and 79 (8%) HSILs. The most common genotype found was HPV 16 (28%) with the following distribution: 21% in NC samples, 31% in ASCUS, 26% in LSILs, and 51% in HSILs. HPV 53 was the second most frequent (16%): 16% in NC, 16% in ASCUS, 19% in LSILs, and 5% in HSILs. The third genotype was HPV 31 (12%): 10% in NC, 11% in ASCUS, 14% in LSILs, and 11% in HSILs. Co-infections were found in 366 samples (34%). In 25%, 36%, 45% and 20% of samples with NC, ASCUS, LSIL and HSIL, respectively, more than one genotype was found.
HPV 16 was the most frequent genotype in our area, followed by HPV 53 and 31, with a low prevalence of HPV 18 even in HSILs. The frequency of genotypes 16, 52 and 58 increased significantly from ASCUS to HSILs. Although a vaccine against HPV 16 and 18 could theoretically prevent approximately 50% of HSILs, genotypes not covered by the vaccine are frequent in our population. Knowledge of the epidemiological distribution is necessary to predict the effect of vaccines on incidence of infection and evaluate cross-protection from current vaccines against infection with other types.
Two HPV vaccines prevent infection with HPV-16 and HPV-18, high-risk (cancer-associated) HPV types which together cause approximately 70% of cervical cancers; one vaccine also prevents HPV-6 and HPV-11, which together cause approximately 90% of anogenital warts. Defining type-specific HPV epidemiology in sexually experienced women will help estimate the potential clinical benefits of vaccinating this population.
To examine HPV epidemiology in a diverse sample of sexually experienced women, and to determine factors associated with high-risk HPV and vaccine-type HPV (HPV-6, -11, -16, -18).
Cross-sectional study of 13-26 year-old women (N=409) who completed a questionnaire and provided a cervicovaginal swab. Swabs were genotyped for HPV using PCR amplification. Logistic regression models were used to determine whether participant characteristics, knowledge, and behaviors were associated with high-risk and vaccine-type HPV.
Most women (68.4%) were positive for ≥ 1 HPV type, 59.5% were positive for ≥ 1 high-risk type, 33.1% were positive for ≥ 1 vaccine-type HPV, and 3.5% were positive for both HPV-16 and -18: none was positive for all four vaccine types. In adjusted logistic regression models, Black race (OR 2.03, 95% CI 1.21-3.41) and lifetime number of male sexual partners (OR 4.79, 95% CI 2.04-11.23 for ≥ 10 vs. ≤ 1 partner) were independently associated with high-risk HPV infection.
HPV prevalence was very high in this sample of sexually active young women, but < 5% were positive for both HPV-16 and HPV-18, suggesting that vaccination could be beneficial for many individual women who are sexually experienced.
human papillomavirus; vaccination; cervical cancer; sexually transmitted infection; epidemiology
We investigated the prevalence of human papillomavirus (HPV) infection and the distribution of high-risk HPV genotypes among 2,308 high-risk Korean women to predict how much the current prophylactic HPV vaccines might affect the prevention of cervical cancer in Korea. HPV DNA was detected in 939 women (40.7%) but only one-third of women were positive for HPV-16 and/or HPV-18, the genotypes used for developing the HPV vaccines. Thus, the development of area-specific HPV vaccines based on dominant HPV genotypes in our country is needed for preventing HPV infection and the development of premalignant lesions in the cervix of Korean women.
Aims—To investigate the distribution and viral load of the most prevalent high risk human papillomavirus (HPV) types 16, 18, 31, 33, and 45 and low risk HPV types 6 and 11 in a variety of cervical lesions.
Methods—One hundred and seventy six cytological specimens from women with different cervical lesions were investigated. For an accurate standardisation of the sample, cervical cells were counted and a volume of the cell suspension processed by polymerase chain reaction-enzyme linked immunosorbent assay (PCR-ELISA). Semiquantitative determinations were achieved in relation to an external reference titration curve.
Results—HPV DNA was detected in 60.2% of the samples. HPV-16 was the prevalent genotype (57.6%), followed by HPV-33, HPV-31, HPV-6, HPV-18, and HPV-45. HPV-11 was not detected. HPV-16 showed a pronounced increase in prevalence with the evolution of cervical disease. Semiquantitative evaluation of the results showed that only HPV-16 DNA could reach very high values (> 1000 genome copies/cell) and a very high HPV-16 load correlated with the severity of cervical disease.
Conclusions—Only HPV-16 load appears to be associated with the severity of cervical disease.
Key Words: human papillomavirus distribution • viral load • cervical lesions
Introduction. Cervical cancer is the most common cancer among Mexican women. The goal of the present study was to determine the prevalence and distribution of HPV types in women from Mexico City. Methods. Our study was conducted in the Clinica de Especialidades de la Mujer de la Secretaría de la Defensa Nacional, Mexico. Random samples were taken from 929 healthy women requesting a cervical Papanicolaou examination. Detection and genotyping of HPV were performed by multiplex PCR, with the HPV4A ACE Screening kit (Seegene). Results. 85 of nine hundred twenty-nine women (9.1%) were infected with HPV. Of HPV-positive women, 99% and 1% had high- and low-risk HPV genotypes, respectively. The prevalence of the 16 high-risk (HR) HPV types that were screened was 43% : 42% (18) were HPV positive and 14% (16) were HPV positive, which includes coinfection. Multiple infections with different viral genotypes were detected in 10% of the positive cases. Abnormal cervical cytological results were found in only 15.3% of HPV-positive women, while 84.7% had normal cytological results. Conclusions. We found a similar prevalence of HPV to previous studies in Mexico. The heterogeneity of the HPV genotype distribution in Mexico is evident in this study, which found a high frequency of HPV HR genotypes, the majority of which were HPV 18.
The association between cervical cancers and human papillomavirus (HPV) is now well established. To estimate the extent of infection with common HPVs among Korean women, we have examined 224 cervical scrapes of various cervical lesions. Detection and typing of HPVs were done by polymerase chain reaction (PCR) using consensus primers followed by restriction enzyme digestion and PCR using type-specific primers. The prevalence of total HPV infection in patients with cervical intraepithelial neoplasia (CIN) and cervical cancer were significantly higher than those in healthy women and patients with atypical squamous cells of undetermined significance (ASCUS). HPV typing in 41 invasive carcinomas of the cervix revealed the prevalence of HPV 16 in 15 cases, followed by HPV 58, 18, 33, 31, 52 and 35. The distribution pattern of HPV types in CIN were not much different from carcinomas. HPV types except HPV 18 had a tendency to show higher prevalence in high-grade squamous intraepithelial lesion (HSIL) than low-grade squamous intraepithelial lesions (LSIL), however, HPV 18 was detected in LSIL but not in HSIL. HPV 18 tended to have the worse clinical stage, although it was not statistically significant. These findings suggest the importance of HPV typing other than HPV 16 and 18 and a different clinicopathologic significance of HPV 18.
Cervical cancer is the leading gynecological malignancy worldwide, and the incidence of this disease is very high in American Indian women. Infection with the Human Papillomavirus (HPV) is responsible for more than 95% of cervical squamous carcinomas. Therefore, the main objective of this study was to analyze oncogenic HPV infections in American Indian women residing in the Northern Plains.
Cervical samples were collected from 287 women attending a Northern Plains American Indian reservation outpatient clinic. DNA was extracted from the cervical samples and HPV specific DNA were amplified by polymerase chain reaction (PCR) using the L1 consensus primer sets. The PCR products were hybridized with the Roche HPV Line Blot assay for HPV genotyping to detect 27 different low and high-risk HPV genotypes. The chi-square test was performed for statistical analysis of the HPV infection and cytology diagnosis data.
Of the total 287 patients, 61 women (21.25%) tested positive for HPV infection. Among all HPV-positive women, 41 (67.2%) were infected with high-risk HPV types. Of the HPV infected women, 41% presented with multiple HPV genotypes. Additionally, of the women infected with oncogenic HPV types, 20 (48.7%) were infected with HPV 16 and 18 and the remaining 21 (51.3%) were infected with other oncogenic types (i.e., HPV59, 39, 73). Women infected with oncogenic HPV types had significantly higher (p=0.001) abnormal Papanicolaou smear tests (Pap test) compared to women who were either HPV negative or positive for non-oncogenic HPV types. The incidence of HPV infection was inversely correlated (p<0.05) with the age of the patients, but there was no correlation (p=0.33) with seasonal variation.
In this study, we observed a high prevalence of HPV infection in American Indian women residing on Northern Plains Reservations. In addition, a significant proportion of the oncogenic HPV infections were other than HPV16 and 18.
Human Papillomavirus; American Indian; Northern Plains; Cervical cancer; Cervical cancer diagnosis
Prevalence of both cervical cancer and Human Immunodeficiency Virus (HIV) infection are very high in India. Natural history of Human Papilloma Virus (HPV) infection is known to be altered in HIV positive women and there is an increased possibility of persistence of HPV infections in this population. Therefore, this study was conducted to understand the epidemiology and circulating genotypes of oncogenic HPV among HIV positive and negative female population in West Bengal, India.
In this hospital-based cross-sectional study, 93 known HIV positive females attending a pre-ART registration clinic and 1106 HIV negative females attending a Reproductive and Child Health Care Clinic were subjected to study. Cervical cell samples collected from the study population were tested for the presence of HPV 16, 18 using specific primers. Roche PCR assay was used to detect other specific HPV genotypes in the cervical cells specimens of HIV positive cases only.
Prevalence of HPV 16, 18 among HIV positive females (32.2%; n = 30) was higher than HIV negative females (9.1%; n = 101). About 53% (23/43) of cases with oncogenic HPV were infected with genotypes other than 16, 18 either as single/multiple infections. HPV 18 and HPV 16 were the predominant genotypes among HIV positive and HIV negative subjects respectively. Oncogenic HPV was not found to be associated with age and duration of sexual exposure. But the presence of HIV was found to a statistically significant predictor oncogenic HPV.
The currently available HPV vaccines offer protection only against HPV 16 and 18 and some cross- protection to few associated genotypes. These vaccines are therefore less likely to offer protection against cervical cancer in HIV positive women a high percentage of who were infected with non-16 and non-18 oncogenic HPV genotypes. Additionally, there is a lack of sufficient evidence of immunogenicity in HIV infected individuals. Therefore, prevention of cervical cancer in HIV positive women must be focused towards early detection of oncogenic HPV & cervical cytological abnormality followed by an appropriate treatment.
Human papillomaviruses (HPVs) are the cause of cervical cancer and possibly a subset of squamous cell carcinomas (SCCs) in other sites. However, the prevalence and distribution of HPV subtypes remain unclear. In the present study, we collected and analyzed 511 paraffin sections of non-cervical SCC from patients in Qingdao, China, for the presence of HPV using polymerase chain reaction (PCR). We identified that 55.77% (285/511) of the samples were positive for HPV infection. There was a significant association between HPV type and the different sites of SCC. An association between HPV-positive cases and tobacco, alcohol, age and tumor differentiation was demonstrated. The information provided by this study may be important for further investigation into the association between HPV and SCC. High-risk HPV subtypes were associated with the malignant degree of SCC. This study provided a theoretical basis for the preventative treatment of non-cervical SCC using HPV vaccines.
squamous cell carcinomas; human papillomavirus genotype; polymerase chain reaction
To investigate the prevalence of, and the risk factors for, cervical infection with 44 types of human papillomavirus (HPV) in a rural area in the Dindigul District, Tamil Nadu, India, we interviewed and obtained cervical cell samples from 1891 married women aged 16–59 years. HPV prevalence was 16.9% overall and 14.0% among women without cervical abnormalities, or 17.7 and 15.2%, respectively, age-standardised to the world standard population. In all, 21.9% of infections involved more than one HPV type. High-risk HPV types predominated, particularly HPV 16 (22.5% of women infected), followed by HPV 56, HPV 31, HPV 33 and HPV 18. Unlike most populations studied in developed countries, HPV prevalence was constant across the age groups. HPV positivity was inversely associated with education level (odds ratio (OR) among women with high school vs no education=0.6) and positively associated with widowhood and divorce (OR=1.7), nulligravidity (OR=2.3), and condom use (OR=2.6). It is unclear how much low clearance of, or frequent reinfection with HPV accounted for the study prevalence of infection in different age groups.
human papillomavirus; cervical neoplasias; India
Infection with human papillomavirus (HPV) is a major risk factor for development of anal squamous cell carcinoma. Despite over 100 genotypes of the virus, HPV 16 and 18 are considered pathogenic as they are seen in the majority of cervical and anal cancers. We have employed a custom microarray to examine DNA for several HPV genotypes. We aimed to determine the accuracy of our microarray in anal cancer DNA for HPV genotypes compared to the DNA sequencing gold standard.
We utilized a sensitive microarray platform to classify 37 types of mucosal HPVs including 14 known high-risk and 23 low-risk types based on cervical cancer data. We utilized DNA from pathologically confirmed cases of anal squamous cell carcinoma. All samples underwent microarray HPV genotyping and PCR analysis.
HPV was detected in 18/20 (90%) anal cancers. HPV genotypes 16 and 18 were present in the majority of specimens, with HPV 16 being the most common. Eighty percent of anal cancers had at least two HPV types. Ten percent of cases (2/20) tested negative using our microarray; DNA sequencing confirmed the lack of presence of HPV DNA in these samples.
Microarray technology is an accurate way to screen for various genotypes of HPV in anal cancer, with 100% correlation with genomic DNA detection of HPV. The majority of anal cancers in our study associated with pathogenic HPV 16 and/or 18. Other HPV genotypes are present simultaneously with HPV 16 and 18, and might contribute to its pathogenesis.
High risk HPV (hrHPV) infection is a necessary cause of cervical cancer but the host genetic determinants of infection are poorly understood. We enrolled 267 women who presented to our cervical cancer screening program in Abuja, Nigeria between April 2012 and August 2012. We collected information on demographic characteristics, risk factors of cervical cancer and obtained samples of blood and cervical exfoliated cells from all participants. We used Roche Linear Array HPV Genotyping Test® to characterize the prevalent HPV according to manufacturer's instruction; Sequenom Mass Array to test 21 SNPs in genes/regions previously associated with hrHPV and regression models to examine independent factors associated with HPV infection. We considered a p<0.05 as significant because this is a replication study. There were 65 women with and 202 women without hrHPV infection. Under the allelic model, we found significant association between two SNPs, rs2305809 on RPS19 and rs2342700 on TYMS, and prevalent hrHPV infection. Multivariate analysis of hrHPV risk adjusted for age, body mass index, smoking, age of menarche, age at sexual debut, lifetime total number of sexual partners and the total number of pregnancies as covariates, yielded a p-value of 0.071 and 0.010 for rs2305809 and rs2342700, respectively. Our findings in this unique population suggest that a number of genetic risk variants for hrHPV are shared with other population groups. Definitive studies with larger sample sizes and using genome wide approaches are needed to understand the genetic architecture of hrHPV risk in multiple populations.
Human papillomavirus (HPV) type-specific distribution was evaluated in genital samples collected from 654 women from the South of Italy undergoing voluntary screening and correlated with cyto-histological abnormalities. HPV DNA was detected in 45.9% of the samples, 41.7% of which had multiple infection and 89.0% had high-risk HPV infection. The prevalence of HPV infection and the rate of multiple infections decreased with age, suggesting natural selection of HPV types with better fitness. In line with other Italian studies, the most common HPV types were HPV-6 and HPV-16, followed by HPV-51, HPV-31, HPV-53, and HPV-66, in women with both normal and abnormal cytology. Cervical intraepithelial lesions grade 2 or 3 were associated with high-risk HPV-16, HPV-18, HPV-31, and HPV-51 infection. These data indicate that prophylactic HPV vaccination is expected to reduce the burden of HPV-related cervical lesions in this population, but also suggest the potential utility of new vaccines with larger type coverage.
Human papilloma virus (HPV) prevalence studies performed in different regions and population groups across Canada would inform public health decisions regarding implementation of anti-HPV vaccines.
A total of 8,700 liquid-based specimens from 8,660 women aged 13–86 from throughout British Columbia were collected. DNA was isolated from 4,980 of these samples and assessed for HPV prevalence and type distribution. HPV was detected by PCR analysis using tagged GP5+/6+ consensus primers to amplify the L1 region of HPV; typing was done by bi-directional sequencing of PCR products.
Overall HPV prevalence was 16.8% (age adjusted 15.5%). Prevalence of high-risk HPV was 13.9, and 10.7% of samples contained HPV16. HPV prevalence was highest in the youngest group of women (<20 years). One-third of HPV positive samples contained more than one HPV type. Percentages of low-grade (LGIL) and high-grade intraepithelial lesions (HGIL) containing high-risk HPV are 52.3 and 79.4%, respectively.
Overall HPV prevalence in this study is within the range of estimates from other studies. The prevalence of HPV16 is higher than what is found in other Canadian and international studies. HPV16 and HPV18 compose a majority of the high-risk virus in this study. Use of current HPV vaccines could considerably reduce HPV-related conditions including cervical cancer and procedures such as colposcopy.
Electronic supplementary material
The online version of this article (doi:10.1007/s10552-009-9365-4) contains supplementary material, which is available to authorized users.
HPV; Typing; Prevalence; Canada
Most data on HPV and antiretroviral therapy (ART) come from high-resource countries with infrequent sampling for HPV pre- and post-ART initiation. Therefore, we examined the frequency of cervical HPV DNA detection among HIV/HSV-2 co-infected women followed monthly for 6 months both before and after initiation of ART in Rakai, Uganda.
Linear Array was used to detect 37 HPV genotypes in self-collected cervicovaginal swabs from 96 women who initiated ART. Random-effects log-binomial regression was used to compare the prevalence of HPV detection in the pre- and post-ART periods and determine other potential risk factors, including CD4 counts and HIV viral load.
Nearly all women had detectable HPV in the 6 months preceding ART initiation (92%) and the cumulative prevalence remained high following initiation of therapy (90%). We found no effect of ART on monthly HPV DNA detection (prevalence ratio: 1.0; 95% confidence interval: 0.96, 1.08), regardless of immune reconstitution or HIV viral suppression. Older age and higher pre-ART CD4 counts were associated with a significantly lower risk of HPV DNA detection.
ART did not impact HPV detection within 6 months of therapy initiation, highlighting the importance of continued and consistent screening, even after ART-initiation and immune reconstitution.
The distribution of HPV genotypes, their association with rigorously confirmed cervical precancer endpoints, and factors associated with HPV infection have not been previously documented among HIV-infected women in India. We conducted an observational study to expand this evidence base in this population at high risk of cervical cancer.
HIV-infected women (N = 278) in Pune, India underwent HPV genotyping by Linear Array assay. Cervical intraepithelial neoplasia (CIN) disease ascertainment was maximized by detailed assessment using cytology, colposcopy, and histopathology and a composite endpoint.
CIN2+ was detected in 11.2% while CIN3 was present in 4.7% participants. HPV genotypes were present in 52.5% (146/278) and ‘carcinogenic’ HPV genotypes were present in 35.3% (98/278) HIV-infected women. ‘Possibly carcinogenic’ and ‘non/unknown carcinogenic’ HPV genotypes were present in 14.7% and 29.5% participants respectively. Multiple (≥2) HPV genotypes were present in half (50.7%) of women with HPV, while multiple ‘carcinogenic’ HPV genotypes were present in just over a quarter (27.8%) of women with ‘carcinogenic’ HPV. HPV16 was the commonest genotype, present in 12% overall, as well as in 47% and 50% in CIN2+ and CIN3 lesions with a single carcinogenic HPV infection, respectively. The carcinogenic HPV genotypes in declining order of prevalence overall included HPV 16, 56, 18, 39, 35, 51, 31, 59, 33, 58, 68, 45 and 52. Factors independently associated with ‘carcinogenic’ HPV type detection were reporting ≥2 lifetime sexual partners and having lower CD4+ count. HPV16 detection was associated with lower CD4+ cell counts and currently receiving combination antiretroviral therapy.
HPV16 was the most common HPV genotype, although a wide diversity and high multiplicity of HPV genotypes was observed. Type-specific attribution of carcinogenic HPV genotypes in CIN3 lesions in HIV-infected women, and etiologic significance of concurrently present non/unknown carcinogenic HPV genotypes await larger studies.