Distribution Of HPV Types Research Articles

Human papillomavirus infection in women attended at a cervical cancer screening service in Natal, Brazil

We analyzed cervical specimens of 202 women, aged 15 to 64 years, attended at Luis Antonio Hospital, Natal, Brazil, to determine the prevalence of HPV and identify the more frequent genotypes and risk factors for HPV infection in women attended at a cervical cancer screening service. Two specimens were collected from each patient: one for cytological examination and the other to detect HPV DNA by PCR, and typing by dot blot hybridization. A total of 54.5% of the sample had normal cytology and 45.5% had cytological alterations. HPV was detected in 24.5% of the cytologically normal women and in 59.8% of those with altered cytology. Both single and double HPV infection increased the likelihood of cytological alterations. Thirteen types of HPV were identified, most of which were high risk. HPV 16 was the most prevalent single-type infection, followed by HPV 58. The most frequent double infection was the association between HPV 56 and 57. The prevalence of HPV in cytologically normal women was greater than that reported for countries on all the continents except Africa. The inverse was observed in women with cytological alterations. The distribution of HPV types was similar to that described for the Americas, with some differences. Multiple sexual partners was the only risk factor showing an association with the presence of HPV infection.

Baseline assessment of prevalence and geographical distribution of HPV types in Chile using self-collected vaginal samples

BackgroundChile has broad variations in weather, economics and population from the far desert north (Region 1) to the cold, icy south (Region 12). A home-based self-collected vaginal sampling was nested in the 2003 Chilean population-based health survey in order to explore the possibility of a type-specific geographical variation for human papillomavirusMethodsThe population was a national probability sample of people 17 years of age and over. Consenting women provided self-collected cervicovaginal swabs in universal collection media (UCM). DNA was extracted and typed to 37 HPV genotypes using PGMY consensus PCR and line blot assay. Weighted prevalence rates and adjusted OR were calculated.ResultsOf the 1,883 women participating in the health survey, 1,219 (64.7%) provided a cervicovaginal sample and in 1,110 (56.2% of participants and 66.5% of those eligible) the samples were adequate for analysis. Refusal rate was 16.9%. HPV prevalence was 29.2% (15.1% high-risk HPV and 14.1% low-risk HPV). Predominant high-risk types were HPV 16, 52, 51, 56 and 58. Predominant low-risk HPVs were HPV 84, CP6108, 62, 53 and 61. High-risk and low-risk HPV rates were inversely correlated between the regions. High-risk HPV prevalence was highest among the youngest women, whereas low-risk HPV increased slightly with age.ConclusionSelf-obtained vaginal sampling is adequate for monitoring HPV in the community, for identifying high-risk areas, and for surveying the long term impact of interventions.

Human papillomavirus infection in women attended at a cervical cancer screening service in Natal, Brazil

We analyzed cervical specimens of 202 women, aged 15 to 64 years, attended at Luis Antonio Hospital, Natal, Brazil, to determine the prevalence of HPV and identify the more frequent genotypes and risk factors for HPV infection in women attended at a cervical cancer screening service. Two specimens were collected from each patient: one for cytological examination and the other to detect HPV DNA by PCR, and typing by dot blot hybridization. A total of 54.5% of the sample had normal cytology and 45.5% had cytological alterations. HPV was detected in 24.5% of the cytologically normal women and in 59.8% of those with altered cytology. Both single and double HPV infection increased the likelihood of cytological alterations. Thirteen types of HPV were identified, most of which were high risk. HPV 16 was the most prevalent single-type infection, followed by HPV 58. The most frequent double infection was the association between HPV 56 and 57. The prevalence of HPV in cytologically normal women was greater than that reported for countries on all the continents except Africa. The inverse was observed in women with cytological alterations. The distribution of HPV types was similar to that described for the Americas, with some differences. Multiple sexual partners was the only risk factor showing an association with the presence of HPV infection.

Comment on the Article: Srodon M, Stoler MH, Baber GB, et al. The distribution of low and high-risk HPV types in vulvar and vaginal intraepithelial neoplasia (VIN and VaIN) Am J Surg Pathol. 2006;30:1513–1518

Comment on the Article: Srodon M, Stoler MH, Baber GB, et al. The distribution of low and high-risk HPV types in vulvar and vaginal intraepithelial neoplasia (VIN and VaIN) Am J Surg Pathol. 2006;30:1513–1518

Prevalence of the most common high‐risk HPV genotypes among women in three new independent states of the former Soviet Union

Type distribution of HPV has been studied in different geographic regions, but the data are scanty from the new independent states of the former Soviet Union. Here the HPV prevalence and distribution of the most frequent high-risk HPV types among 3,187 women at different risk for HPV and cervical intraepithelial neoplasia in Russia, Belarus, and Latvia is reported. HPV detection, type distribution and viral load analysis in DNA samples from cervical scrapes were done with real-time PCR-based assay detecting HPV types 16, 18, 31, 33, 35, 39, 45, 52, and 58. The overall HPV prevalence was 31.2%, HPV16 was the most prevalent type followed by HPV31 and HPV33 group. The overall HPV prevalences in Russia, Belarus and Latvia were 33.4%, 27.5%, and 26.2%. The type distributions were similar in these countries, except for Latvia where HPV39 was the third prevalent genotype. HPV prevalence was highest (40.8%) among women from sexually transmitted disease clinic, followed by 30.9% among gynecological outpatients and 27.2% in screening patients. HPV detection increased with cytological abnormality (P = 0.0001) and lesion grade in the biopsy (P = 0.0001), from 27% to 72% in normal samples to cancer, and from 64% to 77% in cervical intraepithelial neoplasia 1 to cancer. The normalized viral loads varied greatly between and among different HPV-types. The mean log HPV33 group copies/cell increased from negative for intraepithelial lesions to cancer (P = 0.049). Distribution of the most common high-risk HPV-types seems to be similar in these countries as reported in other major geographical regions.

Human papillomavirus typing of invasive cervical cancers in Italy

BackgroundHuman papilloma viruses (HPV) are the necessary cause of invasive cervical cancer (ICC). Of the many different types identified so far, only a few of them account for the great majority of cases worldwide, with geographical differences in their distribution. Data on the local distribution are now of interest in view of the soon-to-come introduction of HPV type-specific prophylactic vaccines.ResultsWe have investigated HPV type distribution in samples of 48 ICC cases occurred in women living in North-East Italy in the years 1997–1999. Cases were extracted from the Venetian Tumour Registry files, as incident cases whose specimens had been processed in two Pathology Departments. Search and typing were performed by polymerase chain reaction (PCR) using GP5+/GP6+ primers, followed by direct sequencing or reverse dot blot. Three cases were PCR negative using the housekeeping primers and hence excluded. One case was negative by all HPV tests used. HPV 16 was present in 32 (72.7%) cases, as single infection in 28, in mixed infection in 4. Of the 44 positive cases, HPV 16 and HPV 18 accounted for 33 (75%), as single or mixed infections. The other high risk HPV types accounted for 11 (25%) of the remaining infections. Of the 32 HPV 16 positive cases, sequencing of the E6 gene could be performed in 25; the prototype isolate was identified in 7, and the variant T350G in 18; in 4 cases one or more additional mutations were present.ConclusionsOur results suggest that HPV 16 has a very high prevalence among women with invasive cervical cancer in Italy; therefore, the use of a prophylactic vaccine for HPV types 16 and 18 could prevent up to 75% of invasive cervical cancers in Italy.

HPV prevalence and type distribution in Denmark: The CLEOPATRE study

HPV prevalence and type distribution in Denmark: The CLEOPATRE study

HPV and cervical cytology

Summary Infection with high-risk human papillomaviruses (HPV) is the major risk factor for the development of cervical neoplasia. It is therefore reasonable to propose that the identification of these viruses may be helpful in the context of cervical screening. High-risk HPV infection is strongly associated with cervical neoplasia, particularly if persistent and present in women over the age of 35 years. Therefore, tests for HPV in the context of cervical cytology only need to identify high-risk HPV types. The strengths of HPV testing are high sensitivity and negative predictive value, indicating that the absence of HPV may be of more clinical value than its presence. However, the clinical application of HPV testing should be evaluated in the context of specific populations. HPV testing may have a role in: (i) primary screening; (ii) the assessment of women with mildly abnormal smears; (iii) post-treatment follow-up; and (iv) quality control of cervical cytology. HPV vaccination, if implemented, is likely to alter the epidemiological characteristics of HPV infection and cervical neoplasia. The effects of vaccination on HPV prevalence, HPV-type distribution and HPV-associated neoplasia will need to be monitored closely.

Prophylactic Human Papillomavirus Vaccine

Cervical cancer kills approximately 270,000 women every year worldwide, being the second most common cancer in women. Cervical cancer is largely preventable through effective massscreening programs. However, such programs are not feasible in developing countries, where approximately 80% of the almost 500,000 new cases of cervical cancer reported annually occur. Despite sufficient evidence for the excellent effectiveness of mass-screening programs in the prevention of cervical cancer, screening policies vary widely even among European countries [1]. Furthermore, the incidence of cervical cancer is increasing, particularly in younger women, due to the inability of the screening programs to tackle the rapidly increasing incidence of human papillomavirus (HPV) infections in adolescents [2]. The primary cause of cervical cancer is persistent high-risk HPV infection, which causes practically all such cases worldwide. Among the approximately 100 types of papillomaviruses characterized so far, approximately 40 types can infect the genital mucosa following sexual transmission. Of those, 16 are oncogenic or so-called high-risk HPV types. HPV-type distribution among women from different geographic populations varies, although HPV-16 is the most prevalent type worldwide [3]. Epidemiologic studies on the prevalence of HPV types in cervical cancer show that approximately 70% are related to HPV-16 and -18, and this is relatively consistent throughout the world [4]. The creation of HPV virus-like particle (VLP) vaccines has been an exceptionally rapid breakthrough. HPV VLPs were described in 1991, and Phase III HPV VLP vaccination efficacy trials have been underway since 1992.

Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis

The proportion of women infected with human papillomavirus (HPV) varies greatly across populations, as might the distribution of HPV types. We aimed to compare HPV-type distribution in representative samples of women from different world regions. Women were randomly selected from the general population of 13 areas from 11 countries (Nigeria, India, Vietnam, Thailand, Korea, Colombia, Argentina, Chile, the Netherlands, Italy, and Spain). A standardised protocol was used for cervical specimen collection. All HPV testing was by GP5+/6+ PCR-based EIA. The proportion of HPV-positive women infected with different HPV types was compared by study area and between pooled regions with age-adjusted odds ratios (ORs) with corresponding 95% floating CIs. 15 613 women aged 15-74 years without cytological abnormalities were included in a pooled analysis. Age-standardised HPV prevalence varied nearly 20 times between populations, from 1.4% (95% CI 0.5-2.2) in Spain to 25.6% (22.4-28.8) in Nigeria. Although both overall HPV prevalence and HPV16 prevalence were highest in sub-Saharan Africa, HPV-positive women in Europe were significantly more likely to be infected with HPV16 than were those in sub-Saharan Africa (OR 2.64, p=0.0002), and were significantly less likely to be infected with high-risk HPV types other than HPV16 (OR 0.57, p=0.004) and/or low-risk HPV types (OR 0.44. p=0.0002). Women from South America had HPV-type distribution in between those from sub-Saharan Africa and Europe. Heterogeneity between areas of Asia was significant. Heterogeneity in HPV type distribution among women from different populations should be taken into account when developing screening tests for the virus and predicting the effect of vaccines on the incidence of infection.

Against which human papillomavirus types shall we vaccinate and screen? The international perspective.

At least 15 types of HPV have been associated with cervical cancer, but current HPV vaccines confer only type-specific immunity. To determine geographic variations in the HPV type distribution in cervical cancer, we carried out a pooled analysis of data from an international survey of HPV types in cervical cancer and from a multicenter case-control study, both co-coordinated by the IARC. Study cases were 3,607 women with incident, histologically confirmed cervical cancer recruited in 25 countries. HPV DNA detection and typing in cervical cells or biopsies were centrally done using PCR assays. Estimates of the potential number of cases prevented by HPV type-specific vaccines and changes in the validity of different HPV screening cocktails were calculated. HPV DNA was detected in 96% of specimens, and 30 different types were detected. The 15 most common types were, in descending order of frequency, 16, 18, 45, 31, 33, 52, 58, 35, 59, 56, 39, 51, 73, 68 and 66. Higher than average proportions of type 16 were found in northern Africa, of type 18 in south Asia, of type 45 in sub-Saharan Africa and of type 31 in Central/South America. A vaccine including types 16 and 18 could potentially prevent 71% of cervical cancers worldwide, but its impact with regard to the percentage of cases potentially prevented would be higher in Asia and Europe/North America. In contrast, a vaccine containing the 7 most common HPV types would prevent about 87% of cervical cancers worldwide, with little regional variation. The impact of modifying the number of types in the screening cocktail tests would be small and probably irrelevant for screening programs.

Occurrence of cervical infection with multiple human papillomavirus types is associated with age and cytologic abnormalities.

Few aspects of the occurrence of infections with multiple HPV types have been described. Since the immunity conferred by vaccines is type-specific, the epidemiology of such coinfections needs to be addressed. The goal of the study was to document the prevalence and incidence of infection with multiple HPV types and the distribution of HPV types in coinfections. In a prospective cohort of 2075 Brazilian women, cervical specimens were collected for cytology and HPV detection. Information on potential risk factors was obtained by interview. The prevalence of HPV coinfections was 3% among cytologically normal women, 10% among women with ASCUS, 23% among those with LSIL, and 7% among those with HSIL. The incidence rate of coinfection declined markedly with age (Ptrend<0.001). Some HPV types co-occurred less frequently than expected, namely, HPV 16 and 18 occurring with other oncogenic HPV types and HPV 6/11. We have observed that occurrence of HPV coinfection was dependent both on age and on the presence of cytologic abnormalities. These results may have implications for vaccine development and for public health decisions about vaccination programs.

Characterization of Human Papillomavirus Infection, P53 and Ki-67 Expression in Cervix Cancer of Mozambican Women

In this study, we aimed at evaluating the distribution of HPV types and the expression of P53 and Ki-67 in cervix carcinomas of Mozambican women. Fourty-seven invasive carcinomas, 10 CIN III, and 10 normal cervix were studied. P53 and Ki-67 expression was examined immunohistochemically. HPV infection and HPV types were detected by PCR (GP5+/bio-GP6+) and enzyme-immunoassay, respectively. Expression of P53 and Ki-67 and detection of HPV were as follows: normal cervix--0%, 10%, and 0%, respectively; CIN III--10%, 0%, and 100%, respectively; invasive carcinomas--50%, 55.5%, and 70%, respectively. HPV 16 was identified in 54% of invasive carcinomas, HPV 31, 33, 35, and 45 in 23%, "unidentified" HPV in 19%, and HPV 18 in 4% of invasive carcinomas. No significant associations were observed between P53 expression, Ki-67 expression, and HPV infection. In conclusion, we observed a high frequency of HPV infection in CIN III lesions and invasive carcinomas from Mozambican women, with HPV 16 representing the most frequent viral type. HPV status was not related to P53 and Ki-67 expression. Both P53 and Ki-67 are associated with invasive cervix carcinomas, mainly of the squamous keratinizing histotype.

Persistence of Human Papillomavirus Infection after Therapeutic Conization for CIN 3: Is It an Alarm for Disease Recurrence?

Objective.The aims of this study were (1) to examine whether HPV DNA is persistently detected in the cervix after therapeutic conization for CIN 3 and (2) to explore whether a patient with persistence of HPV infection is at risk of developing recurrent disease.Methods. Of 74 patients referred with CIN 3, 58 who were tested for HPV DNA in the pretreatment cervical lesions were enrolled in the study. After standard therapeutic conization, patients were followed prospectively at the outpatient clinic. Our follow-up protocol was to follow patients without therapeutic intervention as long as they developed no recurrence or recurrence of CIN 1 or 2, while patients who experienced recurrence of CIN 3 were recommended for reconization or hysterectomy. The polymerase chain reaction for detecting HPV DNA was performed using fresh cell samples from the cervix.Results. In 56 of 58 patients (96.6%), HPV DNAs were detected in their primary cervical lesions prior to conization. With regard to the distribution of HPV types, HPV type 16 family (types 16, 31, and 35) was identified in 28 cases (50.0%), type 18 family (types 18, 33 and 58) in 15 (26.8%), and type X in 18 (32.1%). Up to August 1999, all of the 58 patients have been followed with a mean follow-up period of 31.8 months (range: 12 to 73 months). After treatment, HPV DNA was persistently detected in 11 (19.6%) but negative in 45 (80.4%) of 56 HPV DNA-positive patients. HPV DNA was not detected in both HPV DNA-negative patients. Five of 11 persistently HPV DNA-positive patients (45.5%) developed CIN recurrence, while none of 45 persistently HPV DNA-negative patients did. Thus, there was a significant difference between the recurrence rates of these two groups (P < 0.0001). Both patients who were initially HPV DNA-negative developed no recurrence. Accordingly, the overall recurrence following conservative treatment for CIN 3 was 5 of 58 patients (8.6%).Conclusions. Patients with persistent HPV infection after conization for CIN 3 should be especially closely followed because they are at increased risk of developing disease recurrence.

Common warts from immunocompetent patients show the same distribution of human papillomavirus types as common warts from immunocompromised patients

We studied the papillomaviruses (HPV) found in 131 common warts from 111 immunocompetent patients by amplification of viral DNA sequences with the general-primer-mediated polymerase chain reaction (PCR). The virus types were determined by restriction-enzyme cleavage and reverse-blot analysis. Results were confirmed by using the Southern blot technique. Forty patients harboured HPV 2a, 25 individuals showed HPV 2c and 13 yielded HPV 57. Common warts from 16 patients were induced by a variant of HPV 57. HPV 7 was found in four patients. HPV 1 was identified in two patients, and there was evidence for HPV 4 in only one case. One individual yielded an HPV type which was only weakly related to HPV 2. Three patients were infected by more than one HPV type. PCR did not demonstrate HPV-DNA in warts from six individuals. The distribution and variation of HPV types found in the common warts of immunocompetent patients were similar to the findings in immunocompromised patients reported by other authors.

The role of human papillomaviruses in the pathogenesis and histologic classification of precancerous lesions of the cervix

It is clear that the relation between HPV infection and cervical neoplasia is more complex than initially realized. Preliminary molecular virologic data suggest preferential distributions of low- and high-risk HPV types in CIN that tend to correlate with the morphologic appearance. Thus, mild and moderate dysplasias (CIN I and II) contain a diverse distribution of HPV types, including a minority that have a high risk of malignant potential. HPV, therefore, appears to play a major role as a promoter. Neoplastic transformation is probably determined by specific HPV types but, in addition, requires initiation by some other carcinogenic stimulus, e.g., HSV II, cigarette smoking. Despite numerous studies, performed during the past 30 years, the long-term behavior of dysplasia remains uncertain. The natural history of HPV-associated lesions is unknown. Until this information is available, it is recommended that the conventional dysplasia--CIS or CIN nomenclature be used. The presence of associated viral changes can be considered and added to the diagnosis, e.g., "moderate dysplasia (CIN II) with evidence of papillomavirus infection." Treatment should be the same for all intraepithelial lesions, regardless of the presence of morphologic evidence of HPV. In the future, it may be necessary to modify the classification of precancerous lesions of the cervix if it is shown that a specific HPV type induces a characteristic morphologic alteration or that the HPV type, in and of itself, has greater prognostic significance. Until then, confusion will be minimized and management optimized if the conventional dysplasia--CIS or CIN nomenclature is employed.

Clinical significance of human papilloma virus (HPV) infections of the lower genital tract

Using filter in situ hybridisation for HPV-DNA detection we found among 217 women with positive cervical cytology a positive result in 152 cases (70%). The distribution of the different HPV types showed an association of HPV 6/11 mainly with benign lesions and of HPV 16/18 with obligatory precancer and invasive cervical cancer. In 2652 swabs of cytologically negative patients HPV-DNA was identified in 9.5%. The infection rate for HPV 16/18 in pregnant women was 6.4% against 2.3% in nonpregnant women. In a number of the patients with positive cervical cytology we additionally examined smears from the vagina and vestibulum for HPV-DNA: in 42% of the cases a positive HPV result was obtained in these areas as well. In about 50% of 39 male partners peniscopy revealed penile lesions and HPV-DNA was found in penile smears. A prospective cytological and virological study of cytologically positive patients showed a clear association of HPV 16/18 with progression of cervical lesions. In a cytologically negative group, follow-up examinations revealed HPV-DNA in 31%.