Clinical and virological associations between external anogenital warts and cervical HPV infection in an STD clinic population.

To determine the significance of overt anogenital warts as indicators of human papillomavirus (HPV) infection of the cervix, 177 women attending a Sydney STD clinic were screened for evidence of cervical HPV infection using clinical criteria together with cytology and HPV DNA dot hybridization. HPV DNA probing was also performed on biopsies of 50 exophytic warts. A very high prevalence of both anogenital warts (40%), and of cervical HPV infection (58%) was indicated in this group of women. In the exophytic warts, HPV types 6/11 were most commonly detected, whereas the rates of detection of types 6/11 and 16/18 in the cervix were similar. Of the 87 women with evidence of cervical HPV infection, 57 (66%) had a history of either past or current overt exophytic anogenital warts; while the corresponding figure for the 90 women with no evidence of cervical infection was 45 (50%). Cytological evidence of dysplasia (CIN I-III) was detected in 13 (7%) of the cervical smears: of these, 4 were positive for HPV 16/18 only, 2 for 6/11 only and 4 for both 6/11 and 16/18.     

Symptomatic and asymptomatic cervical infections with human papillomavirus during pregnancy

The prevalence of human papillomavirus (HPV) infection of the cervix was determined in an unselected population of pregnant women presenting to an inner-city Obstetrics Clinic in the first trimester. Cervical scrape specimens were screened for the presence of HPV types 6, 11, 16, 18, and 31 DNA by using three different blot hybridization methods. Specimens from 26 (11.1%) of 234 patients contained HPV DNA sequences. HPV-16 and -31 were detected in six specimens each, whereas HPV-6, -11, and -18 were each identified in three specimens. Five additional specimens contained HPV DNA sequences of undetermined type. Only two of the 26 positive specimens were obtained from patients with genital warts; an additional 12 specimens were from patients with cytological abnormalities. We conclude that cervical HPV infections in some pregnant populations are common and that many such infections are not clinically apparent.     

Human papillomavirus type 31 infection of the uterine cervix in England

A total of 452 uterine cervical scrapes, from two centres in England, has been examined by dot blot hybridisation for the presence of human papilloma virus (HPV) types 6, 11, 16, 18 and 31. HPV DNA was found in 36.5% samples. Twenty-nine of the women were infected with more than one type. Of those with detectable HPV, 14.5% had HPV type 31 infections. This type appears to cause significant infection of the genital tract in England.     

A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions.

DNA from one biopsy sample of invasive cancer of the cervix contained sequences hybridizing with human papillomavirus (HPV) type 11 DNA only under nonstringent conditions. This DNA was molecularly cloned in lambda phage. Under stringent conditions of hybridization it cross-hybridized to a minor extent (less than 0.1%) with HPV types 10, 14, and 15 and showed no homology with DNA of other human HPV types. We therefore propose to designate it tentatively as HPV 16. HPV 16 DNA was used as a probe to test additional cancer biopsy samples from cervical, vulval, and penile cancer, as well as benign genital warts (condylomata acuminata) and cervical dysplasias for the presence of homologous sequences. In 61.1% (11/18) of cervical cancer samples from German patients sequences were found hybridizing with HPV 16 DNA under conditions of high stringency. In contrast, only 34.8% (8/23) of cancer biopsy samples from Kenya and Brazil revealed this DNA. Vulval and penile cancer biopsy samples hybridized to 28.6% (2/7) or 25% (1/4), respectively. Only 2 out of 33 condylomata acuminata contained HPV 16 DNA. Both positive tumors harbored in addition HPV 6 or HPV 11 DNA. The data thus indicate that HPV 16 DNA prevails in malignant tumors, rendering an accidental contamination with papillomavirus DNA from adjacent papillomas rather unlikely. The rare presence in benign genital papillomas in addition to common genital papillomaviruses suggests a dependence of HPV 16 replication on helper virus.     

Concurrent and sequential acquisition of different genital human papillomavirus types

Coinfection with multiple types of genital human papillomavirus (HPV) has been reported, but how frequently it occurs and whether prior infection with specific HPV types inhibits subsequent infection by related types are not known. To address this, 518 women were followed for an average of 2.9 years, and behavioral information and cervical and vulvovaginal swabs for HPV DNA assay were obtained at 4-month intervals. A polymerase chain reaction-based method was used to detect types frequently found in cervical cancers (HPV 16, 18, 31, and 45) and in genital warts (HPV 6 and 11). Concurrent acquisition of multiple types occurred more often than expected by chance. However, no 2 types were more or less likely to be acquired concurrently than any other 2 types. When considering sequential acquisition of HPV types, we found that risk of acquiring a new HPV type was not decreased among those with prior infection by a phylogenetically related or unrelated type (hazard ratio [95% confidence interval], 1.0 [0.4-3.0] and 1.3 [0.8-2.1], respectively).     

Seroepidemiology of low and high oncogenic risk types of human papillomavirus in a predominantly male cohort of STD clinic patients

Human papillomaviruses (HPV) infecting the genital tract are associated with warts and anogenital malignancies. Although HPV is a highly prevalent sexually transmitted disease (STD), the majority of research has focused on female cohorts due to gender specific sequelae. Our objective was to measure the epidemiological features and seroprevalences of HPV-6/11 and 16 in a predominantly male group of STD clinic patients. High-risk individuals (n=687), who attended the public STD clinic were administered a behavioural questionnaire and serum tested for antibodies against HPV-6/11 and HPV-16 capsids via capture enzyme-linked immunosorbent assay. Despite the male predominance in this study, women were significantly more likely to have antibodies against both HPV-6/11 and HPV-16. Condom use appeared to be partially protective against HPV-16 seropositivity only. In conclusion, despite exhibiting increased risk behaviour, men were less likely to be HPV seropositive. Additional studies utilizing male cohorts are warranted to further elucidate this phenomenon.     

Human papillomavirus DNA in unselected pregnant and non-pregnant women

Human papillomavirus (HPV) DNA is associated with genital squamous cell neoplasia, especially types 16, 18, and 31. Several studies, using histopathology and DNA hybridization, have shown an increased prevalence of cervical HPV DNA in pregnant women. We determined the prevalence of HPV DNA and the distribution of specific HPV DNA types in exfoliated cervical cells from 748 randomly selected pregnant and 503 non-pregnant women, using a dot blot DNA hybridization technique. The prevalence of HPV DNA was 9.6% in pregnant women and 8.9% in non-pregnant women. Thus, we found no evidence of higher prevalence of HPV DNA in pregnant women. HPV DNA types 16/18 and 31/33/35 were more common than types 6/11. The prevalence of HPV DNA was highest (15%) in the youngest age groups suggesting an association between young age and the prevalence of HPV DNA.     

Prevalence of human papillomavirus infection in women attending a sexually transmitted disease clinic

The purpose of this study was to determine the prevalence of infection due to human papillomavirus (HPV) types of high and intermediate oncogenic risk, which was most frequently associated with uterine cervical neoplasia. The subjects were 236 prostitutes who visited a sexually transmitted diseases (STD) clinic in a metropolitan area in 1998. Another 95 women who visited a university hospital were selected as a normal control group. A swab sample collected from the uterine cervix and external os was subjected to hybrid capture assays for low-oncogenic-risk HPV types (HPV A; including types 6, 11, 42, 43 and 44) and high- and intermediate-oncogenic-risk HPV types (HPV B; including 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68). Chlamydia trachomatis and Neisseria gonorrhoeae. Fisher's exact test was used for statistical analyses. Among the microorganisms tested, the positive rate for HPV B was the highest both in the women attending the STD clinic (STD group) and in the control group. The positive rate for HPV B in the STD group was 47.5% (112 of 236), and this was significantly higher than the 5.3% (5 of 95) in the control group (p < 0.0001). These findings suggest that HPV examination is recommended for women who visit an STD clinic to assess the future risk of cervical neoplasia.     

Human papillomavirus detection in cervical dysplasias or neoplasias and in condylomata acuminata by in situ hybridization with biotinylated DNA probes.

Specimens from cervical dysplasias or carcinomas and genital condylomata acuminata were retrospectively analysed by in situ hybridization (ISH) with biotinylated DNA probes for human papillomavirus (HPV) types 6, 11, 16 and 18. In the control group no case was positive for HPV DNA. In mild/moderate dysplasias, 4 cases (14%) were positive for HPV 6 or 11 and 2 cases (7%), for HPV 16. In the severe dysplasia/in situ carcinoma group, 9 cases (31%) showed presence of DNA of HPV types 16 or 18. Six invasive carcinomas (20%) were positive for HPV type 16 or 18. Among condylomata acuminata, 22 cases (73%) were positive for HPV types 6 or 11. In all ISH-positive cases only one viral type was detected. No correlation between HPV DNA positivity and histological findings of HPV infection was observed. Although less sensitive than some other molecular biology techniques, in situ hybridization with biotinylated DNA probes proved to be simple and useful for detecting and typing HPV in samples routinely received for histopathological analysis.     

Manifestations of anogenital HPV infection in the male partners of women with anogenital warts and/or abnormal cervical smears.

The prevalence and manifestations of anogenital human papillomavirus (HPV) infection in 154 men, all of whom were the sexual partners of women with either overt anogenital warts or cervical HPV-related abnormalities, were assessed using clinical, histopathological and molecular criteria. Detailed examination of the anogenital region using a colposcope was supplemented by the use of 5% acetic acid to detect possible foci of subclinical HPV infection. Biopsies of warts and aceto-white lesions were examined histopathologically and by HPV DNA hybridization using radiolabelled HPV 6/11 and 16/18 DNA probes. More than two-thirds of the men had clinical indications of genital HPV infection: 37% had apparent macroscopic warts, almost invariably in combination with aceto-white lesions; while 34% had aceto-white lesions only. The overwhelming majority of these lesions (92%) were located on the penis only. However, only 49% of the macroscopic and 29% of the aceto-white lesions showed histological features consistent with a conclusive diagnosis of HPV infection; while the corresponding figures for HPV DNA positivity were 72% and 56% respectively. Current HPV infection was strongly associated with a past history of anogenital warts, but there was little or no correlation between the manifestations of HPV infection in the male and female sexual partners.     

Genital human papillomavirus infection in women who have sex with women: a concern for patients and providers

Certain types of the human papillomavirus (HPV) are sexually transmitted and cause genital warts and cervical neoplasia. Little is known about the epidemiology of HPV among women who have sex with women (WSW), but recent research using amplified techniques for HPV DNA strongly suggests that HPV is sexually transmitted between female sex partners. In a pilot study of 149 WSW in Seattle, Washington, prevalence of HPV as detected by DNA amplification assay was 30%, and was 19% among women reporting no prior sex with men. Although most cervical cancer can be prevented with Pap smear screening by detection of squamous epithelial lesions (SIL), some data suggest that the frequency of Pap smear screening is suboptimal in WSW. Reasons for this are unclear, but may include perceptions by patients and providers that WSW are not at risk for many STD and, by extension, cervical cancer. In our study, WSW who reported no prior sex with men had routine Pap smear screening less frequently than the comparative group, and had a prevalence of SIL of 14%. Combined with the work of other investigators, these data strongly suggest that current recommendations for Pap smear screening among WSW should not differ from those for heterosexual women. WSW and their providers should understand that sex between women may confer a risk of HPV transmission; risk of transmission of other STD, including HIV, deserves further study.     

Development and duration of human papillomavirus lesions, after initial infection

BACKGROUND: To determine the potential value of human papillomavirus (HPV) vaccines, information concerning the incidence and duration of clinically important lesions is needed. METHODS: A total of 603 female university students were followed for a mean duration of 38.8 months. Triannual gynecologic examinations included cervical and vulvovaginal specimen collection for Pap and HPV DNA testing. Women with cytologic evidence of a high-grade squamous intraepithelial lesion (SIL) were referred for colposcopically directed biopsy. RESULTS: Among women with incident HPV infection, the 36-month cumulative incidence of cervical SILs found by cytologic testing (47.2%; 95% confidence interval [CI], 38.9%-56.4%) was higher than that of vaginal SILs (28.8%; 95% CI, 21.3%-38.2%). The median time to clearance of cervical and vaginal SILs was 5.5 and 4.7 months, respectively. Among women with incident HPV-16 or HPV-18 infection, the 36-month cumulative incidence of cervical intraepithelial neoplasia (CIN) grade 2 was 20.0% (95% CI, 10.8%-35.1%), and that of CIN grade 3 was 6.7% (95% CI, 2.5%-17.0%). The 36-month cumulative incidence of clinically ascertained genital warts among women with incident HPV-6 or HPV-11 infection was 64.2% (95% CI, 50.7%-77.4%). CONCLUSIONS: Intraepithelial lesions are common early events among women with incident HPV infection, and the interval between incident HPV-16 or HPV-18 infection and biopsy-confirmed CIN grade 2-3 appears to be relatively short.     

Sexually transmitted diseases and rape: the experience of a sexual assault centre

Epidemiological data and rates of sexually transmitted diseases (STDs) are presented from a group of 90 women screened following rape. Forty-eight (53%) women knew their assailant. In 6 cases multiple assailants were involved. In 21 (23%) rapes weapons were used. Of 47 women examined within 48 hours of rape, 17 (36%) had evidence of genital trauma. Anal injury was common (8 of 11, 73%) in those reporting anal intercourse. Anal assault (17 of 90, 19%) and oral assault (16 of 90, 18%) commonly accompanied rape. STDs were diagnosed in 13 (14.4%) women, 3 having mixed infections. Neisseria gonorrhoeae was isolated in 2 women, Chlamydia trachomatis in 7, Trichomonas vaginalis in 6, genital warts in 2 and Pediculosis pubis in 2 women. Five of 16 cervical cytology results showed abnormalities, 2 were suggestive of CIN. Eleven of 13 women with an STD (84.6%) had been sexually active within the 3 months prior to the rape. Previous sexual activity may be the most relevant factor determining those most at risk of harbouring an STD.     

Effects of the Prophylactic HPV Vaccines on HPV Type Prevalence and Cervical Pathology

Vaccination programs with the current prophylactic HPV vaccines started in most countries around 2008 with introduction of the bivalent Cervarix HPV16/18 vaccine, rapidly followed by Gardasil (HPV6/11/16/18) and, finally, Gardasil 9 (HPV6/11/16/18/31/33/45/52/58), from 2015. Many studies have now confirmed their ability to prevent infection with vaccine-covered HPV types, and the subsequent development of either genital warts and/or cervical neoplasia, although this is clearly more effective in younger women vaccinated prior to sexual debut. Most notably, reductions in the prevalence of vaccine-covered HPV types were also observed in unvaccinated women at the same geographical location, presumably by sexual dissemination of these changes, between vaccinated and unvaccinated women. Furthermore, there are several studies that have demonstrated vaccine-associated HPV type-replacement, where vaccine-covered, high-risk HPV types are replaced by high-risk HPV types not covered by the vaccines, and these changes were also observed in vaccinated and unvaccinated women in the same study population. In light of these observations, it is not entirely clear what effects vaccine-associated HPV type-replacement will have, particularly in older, unvaccinated women.     

Tampons: a novel patient-administered method for the assessment of genital human papillomavirus infection.

Assessment of human papillomavirus (HPV) infection usually requires a speculum examination to collect genital specimens. A technique using tampons as a patient-administered method for the collection of specimens was studied by dot blot hybridization (HPV types 6, 11, 16, 18, 31, and 33) and polymerase chain reaction (PCR). Tampons and cervical scrapes were collected from 48 consecutive women attending a dysplasia clinic. Tampons provided a significantly larger pellet volume (P less than .002) and more DNA (P less than .01) than scrapes. There was a close correlation when samples were analyzed for the presence of HPV DNA. Using dot blot hybridization, 8 cervical scrapes (17%) and 9 tampons (19%) were positive for HPV DNA (90% correlation). By PCR, 35 cervical scrapes (73%) and 33 tampons (69%) were positive for HPV DNA (88% correlation). Thus, tampon specimens are an easy method for assessment of genital HPV infection.     

Coexistence of anal and genital human papilloma virus infection in patients with anal canal carcinoma

The aim of the study was to identify the coexistence of human papilloma virus (HPV) infection in anal carcinoma and in the cervix and glans penis in a population at low risk of sexually transmitted diseases. DNA samples from 14 biopsies of anal carcinoma were analysed by polymerase chain reaction for HPV 6–11, 16, 18, 31–33. The same was done for cervical or glans penis scrapings of the same patients. Among the 9 HPV positive anal squamous carcinomas (64.3%) 6 were HPV 16 positive (42.9%) and 3 were HPV 31–33 positive (21.4%). All the HPV 31–33 positive anal squamous carcinomas were also HPV 31–33 positive in the cytological samples obtained by cervical or glans penis scrapings. In 2 cases (14.3%) HPV 16 was observed both in the anal canal and in the cervix. These data suggest the usefulness of contemporaneous anal and genital evaluation by means of anoscopy and colposcopy with biopsies or scraping as a screening method to identify the presence of HPV without restricting it exclusively to those patients affected by dysplastic lesions of the genital apparatus, sexually transmitted diseases, or to homosexual patients. Received: 20 January 1997 / Accepted in revised form: 3 January 1999     

HPV-beyond cervical cancer (online resource center)

The human papillomavirus (HPV) causes more than 99% of all cervical cancers (see Am J Med Resource Center: http://supplements.amjmed.com/2011/HPV/). Exposure to HPV infections occurs in a high proportion of the overall population; however, 2 safe and effective vaccines, HPV2 and HPV4, are approved for the prevention of HPV-16 and HPV-18 infection, the most common causes of cervical cancer. Additionally, HPV4 prevents HPV-6 and HPV-11-related genital warts. While prevention of cervical cancer in women has been the initial aim of vaccination programs, it has now become apparent that HPV causes other types of cancer as well, including vulvar and vaginal cancers in women, penile cancer in men, and anal cancer in both sexes. Furthermore, these viruses have been implicated in head and neck cancers in both men and women as well. It is estimated that HPV-related cancers occur in 10,000 American males annually, suggesting that limiting vaccination programs to females may be underserving a significant proportion of the population. The efficacy of the 2 available vaccines against oncogenic HPV is more than 90% for both cervical and anal intraepithelial neoplasia. For those receiving the HPV4 vaccine, efficacy against genital warts is nearly 90%. Adverse effects are few and include episodes of syncope in the period immediately following vaccination. Benefits of vaccinating males include reduction in disease burden in men and enhanced herd immunity to reduce disease burden in women.     

Tolerance and efficacy of recombinant human interferon gamma in the treatment of refractory genital warts

PURPOSE: The intralesional administration of recombinant interferon alpha has led to resolution of genital warts in 50 to 70 percent of cases. However, continuous warts do not respond to such treatment, and human papillomavirus (HPV) infection of other anatomic sites remains untreated, so infection may continue to be transmitted. Since interferons have shown promise as effective therapies for genital warts, we decided to investigate the tolerance and efficacy of recombinant human interferon gamma in the treatment of refractory genital warts. PATIENTS and METHODS: Nineteen women and nine men with refractory genital warts were treated in an open-label, dose-response trial of intramuscular recombinant human interferon gamma. RESULTS: Complete responses were seen in two (7 percent) and partial responses were seen in 13 (46 percent). Of 12 women with concomitant cervical HPV infection, eight demonstrated resolution with therapy. Response rates were higher in those patients who had warts less than nine months (73 percent) prior to therapy and in women (63 percent). Responses were not associated with HPV type. Flu-like symptoms during treatment were frequent but well tolerated. Transient abnormal laboratory results were more frequent with daily administration than with three times weekly therapy. Eleven of 16 subjects treated with cryotherapy after treatment with interferon experienced long-term remissions. CONCLUSIONS: In ambulatory patients with refractory genital warts, recombinant human interferon gamma appears to be biologically active and to have few adverse effects. The high efficacy rate achieved in subjects treated with cryotherapy after treatment with interferon suggests that further studies of combination therapy with these modalities are warranted.     

Infection with human papillomavirus: Update on epidemiology, diagnosis, and treatment

Human papillomavirus (HPV) infection is the most common sexually transmitted viral disease worldwide. Low-risk types of HPV (eg, HPV-6 and HPV-11) are the causative agents of genital warts, whereas high-risk types (eg, HPV-16 and HPV-18) have been associated with anogenital cancer, particularly cervical cancer. Cervical cancer remains the second most common cancer in women worldwide. Recent advances have led to a better understanding of how HPV causes cancer on a molecular level and of the immunologic response to HPV. Methods to detect HPV infection have been improved, and a new treatment method for genital warts has been developed. The production of empty capsids of HPV done using recombinant technology has led to the development of serologic assays for HPV. The empty capsids are now the basis of clinical trials of vaccines to prevent HPV infection and disease.     

贵州地区宫颈上皮内瘤变和宫颈浸润癌患者HPV感染状态及其亚型分布

目的观察贵州地区宫颈上皮内瘤变（CIN）和宫颈浸润癌患者人乳头状瘤病毒（HPV）的感染状态及其亚型分布。方法采用导流杂交技术对30例CIN（CIN组）、33例宫颈浸润癌患者（宫颈癌组）、60例自愿接受宫颈HPV感染筛查的妇女（对照组）进行HPV分型检测,所有受检者均来自贵州地区。结果 CIN组HPV阳性13例（43.33%）,宫颈癌组19例（57.58%）,对照组5例（8.33%）。CIN组、宫颈癌组与对照组比较,P均〈0.01。CIN组共检出7种亚型HPV,均为高危型（HR-HPV）,无多型HPV感染（M-HPV）。其中HPV16 7例,HPV31、52各2例,HPV18、33、53、58各1例。宫颈癌组检出5种亚型,亦均为HR-HPV,M-HPV3例。其中HPV16 11例,HPV534例,HPV58 3例,HPV18、59各1例。对照组检出7种亚型,HR-HPV中的HPV16、18、31、39、53、58和低危型HPV的HPV6各1例;M-HPV 1例。CIN组、宫颈癌组HPV16感染率明显高于对照组,P均〈0.05。HR-HPV感染与CIN（OR=8.412,95%CI为2.62~26.99）和宫颈浸润癌（OR=14.929,95%CI为4.74~46.98）紧密相关,且主要与HPV16感染有关（CIN：OR=17.957,95%CI为2.09~154.15;宫颈浸润癌：OR=29.500,95%CI为3.60~242.07）,P均〈0.05。结论贵州地区CIN和宫颈浸润癌与HR-HPV感染密切相关,HPV16为主要感染亚型。