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Human papillomavirus HPVthe primary cause of cervical cancer, is also associated with the development of anal cancer.

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Relatively little is known about the epidemiology of anal HPV infection among healthy females and its relationship to cervical infection. We sought to characterize anal HPV infection in a cohort of adult women in Hawaii.

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Concurrent anal and cervical HPV infection was most prevalent among the youngest women and steadily decreased through age 50 years. By contrast, the prevalence of anal infection alone remained relatively steady in all age groups. Compared with cervical infections, the overall distribution of HPV genotypes in the anus was more heterogeneous and included a greater proportion of nononcogenic types.

A high degree of genotype-specific concordance was observed among concurrent anal and cervical infections, indicating a common source of infection. Nevertheless, the association of anal intercourse with anal HPV infection was limited to those women without accompanying cervical infection. The relationship of anal Spread female anus cervical infection as Spread female anus in this study has implications for the development of anal malignancies in women. Human papillomavirus HPVthe primary cause of cervical cancer, is also associated with the development of anal cancers 12.

Introduction

A high prevalence of HPV infection in the anus has been observed in immunocompromised, HIV-infected men and women 23but relatively little is known about the epidemiology of anal HPV infection among healthy women and its relationship to cervical infection. Although it is established that HPV infection can be transmitted to women through receptive anal intercourse 14alternate routes of transmission may be possible.

Spread female anus part of a longitudinal cohort study of cofactors of persistent HPV infection of the cervix, we Spread female anus to characterize contemporaneous HPV infection in anal specimens collected from cohort participants.

Our objective was to determine the type-specific presence of anal HPV infection, with and without concurrent cervical infection, and to identify factors associated with anal-cervical HPV status. Inwe initiated a multiethnic cohort in Hawaii to identify determinants of persistent HPV infection of the cervix. The study was approved by the Committee on Human Subjects of the University of Hawaii and individual hospital institutional review boards. Written informed consent was obtained from all study subjects.

Women with a prior hysterectomy, who were pregnant within the past year, who had blood-clotting disorders, or who could not speak and understand English were ineligible to Spread female anus. A total of 2, ethnically diverse women were recruited from five clinic sites in Honolulu, HI, and followed with repeat visits at 4-month intervals. Study sites included Spread female anus urban medical center-based clinic servicing a largely Spread female anus population, two university-based health clinics, a health maintenance organization, and a hospital-based clinical research center.

A Dacron swab and cytology brush were used consecutively to sample the entire ectocervix and endocervix, including the entire transformation zone. The swab and brush were then each placed in separate vials of 1.

The collection of anal specimens was optional for study subjects.

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Following the cervical specimen collection, an exfoliated anal cell specimen was obtained using a Dacron swab moistened with sterile water. The swab was placed in 1. An interviewer-administered survey was conducted at each study visit. At enrollment, a short survey queried social and demographic information as well as information on tobacco and alcohol use.

The survey at the subsequent follow-up visit included questions regarding medical, sexual, and reproductive histories as well as tobacco and alcohol use. The present report focuses on baseline anal and cervical HPV DNA results as well Spread female anus survey data collected at baseline and the second follow-up visit. DNA was extracted from anal and cervical specimens Spread female anus commercial reagents Qiagen, Inc.

Negative controls were void of template.

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PCR was done in a well format on a Perkin-Elmer as follows: The original DNA specimens from HPV-positive specimens were subsequently genotyped using a reverse line blot detection method for 37 different HPV types, including 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73, 81, 82, 83, 84, CP, and IS39 67. PCR products were denatured and hybridized Spread female anus a nylon membrane containing the immobilized HPV probes.

Amplicons hybridized to probes were detected using streptavidin-horseradish peroxidase—mediated color precipitation.

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HPV-positive specimens that were subsequently found to be negative in the genotyping assay were considered to be unclassified HPV-positive specimens. Women providing and not providing anal specimens were compared by unconditional multiple logistic regression. Evaluation of anal-cervical HPV status was made using women negative for both anal and cervical infection as the reference. For both analyses, continuous variables, such as lifetime number of sexual partners, were categorized, and indicator variables were created representing the different variable categories.

The trend variable was assigned the median for the appropriate category. Cervical specimens were Spread female anus from all 2, women enrolled in this study. Among the participating women, Spread female anus, Compared with women not providing anal specimens, women providing anal specimens Spread female anus more likely to be White and more likely to have engaged in anal intercourse Table 1.

There were no differences between the two groups in cervical HPV infection at baseline. Characteristics of study participants by provision of anal specimens, Hawaii female HPV cohort, to Among the women enrolled in the study, 2, Among the 1, women agreeing to provide anal specimens, 1, Overall, 35 distinct HPV genotypes were detected in both anal and cervical specimens. HPV genotypes tended to be more diverse among anal specimens compared with cervical specimens, whereas oncogenic HPV types were much more common in cervical specimens than in anal specimens.

Spread female anus contrasts were most apparent between infections limited to either the anus or the cervix Fig. There seemed to be no pattern of genotypic concordance or discordance by type data not shown. Multiple genotypes were also more common in concurrently infected women.

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This concurrently infected group averaged 2. HPV-negative anus and cervix women were the oldest with a mean age of Relationship of HPV status in paired anal-cervical specimens with selected characteristics, Hawaii female cohort, to A history of Chlamydia infection and nulliparity were associated with concurrent anal and cervical infection.

Early age at initial sexual intercourse was a risk factor for both cervical infection alone and concurrent anal-cervical infection but not for anal HPV infection alone.

A positive association of lifetime number of sexual partners was consistent among all three Spread female anus cervical HPV infection alone, concurrent anal and Spread female anus infection, and anal infection alonealthough the magnitude of the association was attenuated among those with anal HPV infection.

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A history of anal intercourse was associated with anal infection alone OR, 1. Recent anal intercourse within the past 3 monthshowever, was not associated with anal infection alone for any group. We further explored the relationship of age by anal-cervical HPV status Fig.

The prevalence of cervical Spread female anus infection without accompanying anal infection also showed an overall although less dramatic decrease with age. In contrast, the prevalence of anal infection alone remained steady at all age groups.

HPV, the primary cause of cervical cancer, is also associated with the development of anal cancers 12. The Spread female anus of anal to cervical infection as described in our findings has implications for the development of Spread female anus malignancies in women. The incidence of anal cancer has increased among both men and women in the United States over the past 2 decades, and rates have been comparable among sexes in recent years 89.

The histology of the anus shares important parallels with the cervix, including a transitional area of the epithelium, analogous to the cervical transformation zone, where columnar and squamous epithelium meet 2.

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Furthermore, there is evidence that HPV-induced malignancies of the Spread female anus share a natural history similar to that of the cervix beginning with viral infection and progressing to dysplastic lesions and, finally, invasive cancer Our results suggest that anal HPV infection is a common infection among healthy, sexually active females with prevalence comparable with cervical infection.

It also suggests that anal and cervical HPV infections are strongly correlated. The multifocal nature of HPV-related disease has been shown in previous studies whereby it is not uncommon for anal and cervical squamous intraepithelial lesions to occur concurrently or consecutively 11 A high degree of genotype-specific concordance was observed among concurrent infections, indicating a common source of infection, such as vaginal and anal intercourse with the same infected partner or Spread female anus.

Nevertheless, anal intercourse was not associated with HPV infection among concurrently infected women. Recent studies have observed a lack of association between anal intercourse and anal HPV infection among women This suggests alternate routes of transmission, including sexual and nonsexual means. There is evidence that HPV can be transmitted to the genitals through nonpenetrative sexual contact involving the fingers or mouth of partners Cross-contamination of specimens during the collection process was not likely.

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Indeed, these women were older and less likely to be Japanese and Hawaiian. Unlike the other two groups cervical infection alone and concurrent anal and cervical infection where risk of infection decreased with age, age was not associated with anal HPV infection Spread female anus.

A history of ever engaging in anal intercourse was associated with increased risk of HPV only among these women with infection limited to the anus and no association was observed for recent anal intercourse. With the exception of anal intercourse, associations with sexual risk factors were either absent or attenuated among this group compared with other groups. Our results suggest that different HPV genotypes may have different tropism to the anus compared with the cervix.

The overall distribution varied considerably in the anus compared with the cervix. Anal genotypes were more heterogeneous with Spread female anus higher proportion of nononcogenic types. The predominance of nononcogenic types in the anus compared with the cervix may explain the relatively low incidence of anal cancers compared with cervical cancers.

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Multiple genotypes were more common in both the anus and the cervix of women with concurrent anal-cervical infections compared with women with infections limited to either site alone. This observation together with the high level of genotypic concordance may indicate that women with concurrent infection represent a group that, due to immune function or other factors, are more susceptible to infections with different HPV types Spread female anus well as multifocal infections affecting more than one anatomic area.

The proportion of unidentified genotypes in infections limited to either the anus or the cervix was substantially higher than in concurrent anal-cervical infections.

A possible explanation is that Spread female anus infections represent infections of higher viral levels and are therefore more likely to be transmitted between the cervix and the anus either through sexual or nonsexual means and also more successfully genotyped through the PCR hybridization—based assay. By contrast, anal specimens come from the nonmucus, keratinized epithelium of the anus. Others have reported difficulty in obtaining nuclear DNA markers from highly keratinized cells, Spread female anus may have a substantial proportion of anucleated cells Our ability to evaluate the relationship of anal intercourse and anal HPV infection was limited by sampling biases.

Information on sexual practices was limited to those women who returned for the second visit when the comprehensive survey was administered. Asian and Hawaiian populations were less likely to consent to provide anal specimens.

This may be attributed to cultural issues surrounding comfort level in undergoing the anal specimen collection process. Younger women were also less likely Spread female anus provide anal specimens.


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