Number Of Human Papillomavirus Types Research Articles

HPV prevalence among young adult women living with and without HIV in Botswana for future HPV vaccine impact monitoring

IntroductionIn 2015, Botswana introduced quadrivalent human papillomavirus (HPV) vaccine for girls aged 9–13 years. To establish a baseline HPV prevalence for future HPV vaccine impact monitoring, we evaluated HPV prevalences among the youngest unvaccinated women in Botswana and compared HPV prevalences among women living with HIV (WLHIV) and without HIV.MethodsWomen aged 18–22 years were recruited from the University of Botswana and HIV clinics in Gaborone from October 2019–January 2021. Demographic and behavioral characteristics were self-reported during structured interviews; HIV clinical characteristics were abstracted from medical charts. Self-collected vaginal swabs were tested for 28 HPV types using Seegene Anyplex II HPV28. We compared prevalence of any HPV, high risk (HR)-HPV, and quadrivalent HPV vaccine types (HPV6/11/16/18) among WLHIV and women without HIV and evaluated risk factors for prevalence of HR-HPV.ResultsA total of 306 WLHIV and 500 women without HIV were recruited. Compared to women without HIV, WLHIV were more likely to be sexually experienced (86.6% versus 74.4%) and have ≥ 3 lifetime sex partners (55.3% versus 27.8%). All HPV type prevalences were significantly higher among WLHIV compared to women without HIV, including prevalence of any HPV (82.7% versus 63.0%), HR-HPV (72.9% versus 53.8%), and quadrivalent vaccine HPV types (34.3% versus 21.0%). Among WLHIV, there were no differences between those perinatally and non-perinatally infected for HPV prevalences, number of HPV types detected, CD4 count, or viral load.ConclusionsOver one-third of WLHIV and nearly a quarter of those without HIV had vaccine-type HPV detected. This study supports need for the national HPV vaccination program in Botswana and provides important baseline data for future evaluation of impact of the program.

Beta Human Papillomavirus and Merkel Cell Polyomavirus in Skin Neoplasms

Beta Human Papillomavirus and Merkel Cell Polyomavirus in Skin Neoplasms

Trends in prevalence in human papillomavirus types and their association with cervical dysplasia: an analysis on 15 138 women over 20 years.

To investigate trends in prevalence of various human papillomavirus types in order to assess the unmet clinical needs for women affected by human papillomavirus-related disease. Data of consecutive 15 138 patients undergoing human papillomavirus DNA testing from 1998 to 2018 were retrospectively identified. Human papillomavirus types were classified at high-risk according to the classification of the International Agency for Research on Cancer. The International Agency for Research on Cancer included seven human papillomavirus types covered by nine-valent vaccine and five not yet covered by any available vaccines. Overall, 4159 (65.3%), 1500 (23.5%) and 714 (11.2%) women had human papillomavirus types covered by nine-valent vaccination, not covered by nine-valent vaccination and co-infections of human papillomavirus types of both groups. At least one high-risk human papillomavirus type(s) was detected in 1241 patients with genital dysplasia: 832 (67.1%), 291 (23.4%) and 118 (9.5%) women had human papillomavirus types covered by nine-valent vaccination, not covered by nine-valent vaccination and co-infections of human papillomavirus types of both groups. Over the twenty-year study period, the number of human papillomavirus types not covered by nine-valent vaccine increased dramatically (from 4 to 16%; P < 0.001, P for trend). Similarly, looking at patients with genital dysplasia, high-risk human papillomavirus types not covered by nine-valent vaccine increased from 3 to 13% (P < 0.001, P for trend). Our data highlight that human papillomavirus types covered by nine-valent vaccine represent are the main types associated with genital dysplasia. However, over the study period, we observed an increasing prevalence of confections and high-risk human papillomavirus types not covered by the nine-valent vaccine, thus suggesting the need of developing more complete vaccines against human papillomavirus.

A Pilot Study of the Immunologic, Virologic, and Pathologic Consequences of Intra-anal 5% Imiquimod in HIV-1-Infected Men With High-Grade Squamous Intraepithelial Lesions.

Imiquimod can be used to treat internal anal high-grade squamous intraepithelial lesions. In HIV-1-infected individuals there is a theoretical concern for increased HIV replication in anorectal tissue secondary to imiquimod-induced mucosal inflammation. The purpose of this study was to assess local virologic, immunologic, and pathologic effects of imiquimod treatment in HIV-infected individuals. This was a pilot study at a single academic center. The study was conducted at the University of Pittsburgh Anal Dysplasia Clinic. HIV-1-infected individuals with biopsy-confirmed internal anal high-grade squamous intraepithelial lesions were included. Imiquimod cream was prescribed for intra-anal use 3 times per week for 9 weeks. Anal human papillomavirus typing, anal and rectal tissue HIV-1 RNA and DNA quantification, cytokine gene expression, and anal histology were measured. Nine evaluable participants (1 participant was lost to follow-up) were all white men with a median age of 46 years (interquartile range = 12 y) and a median CD4 T-cell count of 480 cells per cubic millimeter (interquartile range = 835). All were taking antiretroviral therapy, and 7 of 9 had HIV-1 RNA <50 copies per milliliter. The median dose of imiquimod used was 27.0 (interquartile range = 3.5), and there was a median of 11 days (interquartile range = 10 d) from last dose to assessment. There was no progression to cancer, no significant change in the number of human papillomavirus types detected, and no significant change in quantifiable cytokines/HIV-1 RNA or DNA levels in anal or rectal tissue. Seven (35%) of 20 high-grade lesions resolved to low-grade squamous intraepithelial lesions. The study was limited by the small number of participants and variable time to final assessment. Intra-anal imiquimod showed no evidence of immune activation or increase in HIV-1 viral replication in anal and rectal tissue and confirmed efficacy for intra-anal high-grade squamous intraepithelial lesion treatment morbidity. See Video Abstract at http://links.lww.com/DCR/A498.

Impact of bivalent human papillomavirus (HPV) vaccination upon the risk of acquisition of other HPV types

The first human papillomavirus (HPV) vaccine was approved by the FDA in 2006, protecting against 2 carcinogenic types, 16 and 18. There is limited information about whether that vaccination may affect the prevalence of other HPV types in a community over time. Our study aimed to examine this issue. We used published data from The Costa Rica Vaccine Trial. Women were vaccinated with either the Cervarix® HPV vaccine or the hepatitis A vaccine (the control group). Based upon laboratory data, each of these arms can be divided into a naive cohort with no evidence of HPV infection on trial entry and the rest considered a non-naive cohort with baseline infection with HPV.At the end of a 4-year follow-up, women in the combined non-naive cohort had higher rates of HPV (mean number of HPV types detected per woman = 1.22) compared to the combined naive cohort (mean number of HPV types detected per woman = 0.917), consistent with their presumptive higher risk profile upon study entry. However, there was considerable variation by HPV type. Comparing those vaccinated against HPV to the control group, those in the non-naive cohort had an increased prevalence of HPV type 35 (RR=1.37, 95%CI [0.88, 2.11]), and significantly increased prevalence of HPV types 51 and 59 (RR=1.34 [1.03, 1.74] and 1.86 [1.15, 3.00]) respectively). This could be the result of increased HPV infection with these types after HPV 16/18 vaccination or HPV infection before trial entry. Among the naive cohort, there was decreased prevalence in the HPV vaccine arm of HPV type 31 (RR=0.30, 95% CI [.12, .79]) and type 45 (RR=0.18, 95% CI [0.02, 1.46]), suggesting possible cross protection to these HPV types.The protective effects from the bivalent HPV vaccine in the non-naive cohort further support the current public health practice of administering the HPV vaccine to young women, without regard to baseline HPV status.On December 10, 2014, the FDA approved Gardasil 9®, which vaccinates for an additional 5 carcinogenic types of HPV (31, 33, 45, 52 and 58). The addition of these types to the HPV vaccine will be beneficial in decreasing infection with these HPV types, but our analysis looks at the possible implications of how this can affect acquisition types not featured in the vaccine. There was a high prevalence of HPV types 16, 51 and 52 among the total cohort. Types 51 and 52 are not in the prior HPV vaccines and type 51 is not in the new Gardasil 9® vaccine, so type 51 may continue at a high prevalence in some geographic areas and may pose especial risk in the coming years. The prevalences of the various HPV types differ, sometimes substantially, by region. Therefore, further studies examining the prevalence of HPV types over time by geography will be critical for providing guidance to vaccine manufacturers, as well as screening guidelines for clinicians.

HPV infection-associated anogenital cyto-colpo-histological findings and molecular typing in HIV-positive women.

HIV and human papillomavirus (HPV) coinfection is increasing, especially in the anal canal (AC) and cervico-vaginal regions. We identified anal epithelium abnormalities related to high-risk HPV (HR-HPV) lesions in the lower genital tracts (LGTs) of HIV-positive women, described the HPV genotypes identified, and assessed the expression of E6/E7 oncogenes in coinfected patients. Ninety-eight women were enrolled in groups combining HIV status and presence or absence of HPV in the LGT. Anal and cervical smears were collected for cytology and HR-HPV assays using Cobas(®) and/or PapilloCheck(®). Samples with highly oncogenic HPV genotypes were confirmed by NucliSENS EasyQ(®). Forty-two HIV-positive (25-52; mean age 39.5) and 56 HIV-negative (18-58; mean age 35.7) patients were included. E2 and C1 groups presented AC alterations (P = 0.002); altered images for high-resolution anoscopy were higher in E1 and C2 (P < 0.001). Of the 29 women with alterations, 41.38% were HIV-negative and 58.62% were HIV-positive (P < 0.001). HIV-positive patients accounted for 29% of the anal high-grade squamous intraepithelial lesions (P = 0.015). The Cobas(®) positive result frequency was higher in three AC groups than in the other groups. There was variation in the number of HPV types in the cervico-vaginal samples among the study groups (P < 0.001). Anal cytology and anoscopy showed more altered findings in HIV-positive patients with HPV in the LGT. HR-HPV anal infections by various genotypes are common and are associated with cervical infections in HIV-positive patients. E6/E7 expression is apparently more common in the AC of HIV-positive women.

Prevalence of human polyomavirus DNA in eyebrow hairs plucked from patients with psoriasis treated with TNF inhibitors

Background Tumour necrosis factor alpha (TNF-a) inhibitors are associated with an increased risk of infections and with a still debatable risk of skin cancer. Furthermore, cutaneous human papillomavirus (HPV) infection may be involved in skin cancer. Objectives Our primary objective was to assess the HPV DNA prevalence in psoriasis patients treated with TNF inhibitors and the secondary objective was to assess the same parameter before and during treatment. Methods Plucked eyebrow hairs were collected from 151 consecutive patients with moderate to severe chronic plaque psoriasis, including 48 patients treated with anti-TNF-a agents, 21 patients treated with methotrexate (MTX) and 82 patients with no previous systemic treatment. Among them, 38 patients were subsequently treated with either MTX or anti-TNF-a agents. HPV genotyping was performed using the HPV type-specific E7 PCR bead-based multiplex allowing the detection of 27 genus-a types, 25 genus-b types, 16 genus-c types and one single genus-l type. Follow-up provided a total of 972.7 person-months of overall exposure for patients treated with TNF inhibitors and 326.9 person-months for patients treated with MTX. Results Our data confirm the high prevalence of b-HPV infection in healthy skin of psoriasis patients (68.9%), with no significant difference between untreated patients (64.6%), patients treated with MTX (76.2%) and patients treated with anti-TNF-a agents (72.9%). The mean number of different HPV types and the distribution of HPV types were similar in different groups of patients. Moreover, in prospectively treated patients, we did not observe any change in the HPV DNA prevalence in the distribution of HPV types and the number of HPV types after a mean duration of treatment of 332 39.8 days. Conclusion Despite the small number of patients in our cohort, our results are quite encouraging in view of the increased use of anti-TNF-a agents in different auto inflammatory immune diseases.

Current status of human papillomavirus vaccines.

Cervical cancer is a malignant neoplasm arising from cells that originate in the cervix uteri. It is the second most prevalent cancer among women. It can have several causes; an infection with some type of human papillomavirus (HPV) is the greatest risk factor for cervical cancer. Over 100 types of HPVs have been identified, and more than 40 types of HPVs are typically transmitted through sexual contact and infect the anogenital region. Among these, a number of HPVs types, containing types 16 and 18, are classified as "high-risk" HPVs that can cause cervical cancer. The HPVs vaccine prevents infection with certain species of HPVs associated with the development of cervical cancer, genital warts, and some less common cancers. Two HPVs vaccines are currently on the global market: quadrivalent HPVs vaccine and bivalent HPV vaccine that use virus-like particles as a vaccine antigen. This review discusses the current status of HPVs vaccines on the global market, clinical trials, and the future of HPVs vaccine development.

Prevalence of human Papillomavirus DNA in eyebrow hairs plucked from patients with psoriasis treated with TNF inhibitors

Tumour necrosis factor alpha (TNF-α) inhibitors are associated with an increased risk of infections and with a still debatable risk of skin cancer. Furthermore, cutaneous human papillomavirus (HPV) infection may be involved in skin cancer. Our primary objective was to assess the HPV DNA prevalence in psoriasis patients treated with TNF inhibitors and the secondary objective was to assess the same parameter before and during treatment. Plucked eyebrow hairs were collected from 151 consecutive patients with moderate to severe chronic plaque psoriasis, including 48 patients treated with anti-TNF-α agents, 21 patients treated with methotrexate (MTX) and 82 patients with no previous systemic treatment. Among them, 38 patients were subsequently treated with either MTX or anti-TNF-α agents. HPV genotyping was performed using the HPV type-specific E7 PCR bead-based multiplex allowing the detection of 27 genus-α types, 25 genus-β types, 16 genus-γ types and one single genus-μ type. Follow-up provided a total of 972.7 person-months of overall exposure for patients treated with TNF inhibitors and 326.9 person-months for patients treated with MTX. Our data confirm the high prevalence of β-HPV infection in healthy skin of psoriasis patients (68.9%), with no significant difference between untreated patients (64.6%), patients treated with MTX (76.2%) and patients treated with anti-TNF-α agents (72.9%). The mean number of different HPV types and the distribution of HPV types were similar in different groups of patients. Moreover, in prospectively treated patients, we did not observe any change in the HPV DNA prevalence in the distribution of HPV types and the number of HPV types after a mean duration of treatment of 332 ± 39.8 days. Despite the small number of patients in our cohort, our results are quite encouraging in view of the increased use of anti-TNF-α agents in different auto inflammatory immune diseases.

Validation of the SPF 10 LiPA Human Papillomavirus Typing Assay Using Formalin-Fixed Paraffin-Embedded Cervical Biopsy Samples

Lower levels of performance of human papillomavirus (HPV) typing assays in studies using formalin-fixed paraffin-embedded (FFPE) tissue compared to those using exfoliated cervical cells have been reported. The interpretation of current studies is limited by bias in inclusion criteria, sample matching, and methods of cell collection. We aimed to validate FFPE tissue for typing by the use of the SPF(10) LiPA assay, comparing cervical scrapings to punch and cone biopsy specimens. We examined 165 paired cervical scraping and FFPE punch biopsy samples, and 66 paired FFPE punch and cone biopsy samples. HPV typing was performed using the SPF(10) LiPA assay. Kappa statistics were used to measure interrater agreement. The overall agreement with respect to HPV status was 100%. For 74.5% of subjects (kappa = 0.6147), the same numbers of HPV types were detected in scraping and biopsy specimens. The overall positive typing agreement was 95.4% (range, 93.4 to 97.3) for 441 out of 484 individual HPV type analyses. Agreement was good for HPV-39, -42, -43, and -70 (kappa = 0.6506 to 0.7166), excellent for HPV-6, -16, -18, -31, -33, -35, -40, -51, -52, -56, -58, and -66 (kappa = 0.8499 to 0.9665), and absolute for HPV-11, -44, -45, -53, and -68. In 43.9% of cases (kappa = 0.247), the same numbers of HPV types were found in punch and cone biopsy specimens. Overall positive agreement for typing was 86.8% (range, 82.5 to 91.1) for 204 out of 266 individual HPV type analyses. More infections by HPV-18, -33, -51, and -52 were detected in cone specimens. HPV typing by SPF(10) LiPA performed equally well for cervical scraping specimens and standard pathological material. Some viral types are preferentially detected in cone specimens, likely reflecting better sampling of diseased epithelium and endocervix tissue.

Human papillomavirus-associated induction of human β-defensins in anal intraepithelial neoplasia

Antimicrobial peptides and proteins (AMPs) are widely distributed effector molecules of the innate immune system with well-known antibacterial activity. However, there is a paucity of information regarding antiviral effects of AMPs. The present study was performed to analyse expression of AMPs in human papillomavirus (HPV)-associated anal skin lesions of human immunodeficiency virus (HIV)-positive men who have sex with men (MSM), a special high-risk group for persistent HPV infections and anal dysplasia. Skin lesions were analysed for the presence of LL-37, RNase 7, and human beta-defensin (hBD)-1, hBD-2 and hBD-3. Moreover, HPV typing and HPV DNA load determination for HPV types 6, 11, 16, 18, 31 and 33 were performed to evaluate possible correlations between expression of AMPs and lesional HPV types. Skin biopsies of 45 HIV-positive MSM with anal intraepithelial neoplasia (AIN), anal condylomata acuminata or unaffected anal mucosa, as well as condylomata acuminata of eight HIV-negative MSM, were analysed for AMP mRNA expression. Additionally, immunohistochemical analysis for hBD-2 and hBD-3 was performed in a total of 45 samples. hBD-2 and hBD-3 gene and protein expression was significantly increased in both AIN and condyloma, whereas LL-37, RNase 7 and hBD-1 gene expression did not differ significantly from unaffected anal mucosa. AMP expression correlated neither with the number of HPV types nor with the high-risk and low-risk HPV DNA loads of the quantified types. No significant differences in AMP expression were observed in condylomata of HIV-positive and HIV-negative MSM. hBD-2 and hBD-3 expression was shown to be significantly upregulated in HPV-associated anal skin lesions of both HIV-positive and HIV-negative MSM. Their biological significance in the innate immunity against these lesions needs further research.

Imiquimod Leads to a Decrease of Human Papillomavirus DNA and to a Sustained Clearance of Anal Intraepithelial Neoplasia in HIV-Infected Men

Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)-associated precursor lesion of anal carcinoma, is highly prevalent in HIV-infected men having sex with men (MSM). This prospective follow-up study evaluated the long-term results of imiquimod treatment of AIN in 19 HIV-infected MSM. Standardized follow-up examinations included high-resolution anoscopy, anal cytology/histology, HPV typing, and DNA load determination for HPV types 16, 18, 31, and 33. Mean follow-up time was 30.3 months. A total of 74% (14/19) of the patients remained free of AIN at the previously treated site. Five patients (26%) had recurrent high-grade AIN after a mean time of 24.6 months. At the end of follow-up, the numbers of HPV types as well as high-risk HPV-DNA loads were significantly lower than before therapy. During follow-up, 58% of all patients (11/19) developed new anal cytological abnormalities in previously normal, untreated anal regions. 55% of these new AIN lesions were high-grade lesions and most of them were located intra-anally and associated with high-risk HPV types not detectable before therapy. These results demonstrate that imiquimod leads to a high rate of long-term clearance of AIN in HIV-positive men together with a prolonged decrease of high-risk HPV-DNA load. However, new AIN lesions associated with previously undetected HPV types frequently occur in untreated areas.

Prophylactic HPV vaccines – an update

Cervical cancer affects nearly half a million women each year, and nearly half of them die. The greatest problem is in the developing world, though even in the UK nearly 3 000 women develop cervical cancer each year.Infection with certain types of sexually transmitted human papillomavirus (HPV), in particular HPV 16 and HPV 18, is the main cause of cervical cancer. It has been shown that 99.7% of cervical cancers contain HPV DNA. Infection with HPV appears to be extremely common in young people, but is usually transient. It appears that the presence of HPV is more meaningful in older women (over 30), who have persistent infection.Screening tests detect cellular abnormalities early, but the ultimate solution to a viral disease is obviously a vaccine. A problem is the number of cervical cancer HPV types which need to be included (potentially 15). Two vaccines have proved extremely effective in clinical trials, with recent results demonstrating 100% efficacy against persistent HPV infection and development of CIN up to five years of follow up (Harper 2006, Villa 2005). One of these (Gardasil, recently licensed) contains four HPV types and would thus protect against genital warts (types 6 and 11) as well as the commonest cervical cancer HPV types (16 and 18). Gardasil®is licensed for children and adolescents aged 9 to15 years and adult females aged 16 to 26 years. The NHS cost of one dose of the vaccine is £80.50, three doses are required to provide protection.In clinical trials Gardasil® showed 100% (95% CI 92.9 – 100) efficacy in the prevention of CIN2/3 related to HPV 16 and 18. Gardasil® was also 100% (95% CI 41.4 – 100) effective in preventing VIN2/3 related to HPV 16 and 18. In addition, there were no cases of high‐grade vaginal lesions (VaIN2/3) due to HPV types 16 and 18 in those who received Gardasil®, compared to five in those who received placebo (not statistically significant). Gardasil has shown 98.9% (95% CI 93.7–100) efficacy in the prevention of genital warts related to HPV types 6 and 11 (Siddiqui &amp; Perry, 2006).The other vaccine (Cervarix) contains types 16 and 18, and thus targets cervical cancer alone. Recent data (Harper 2006) have suggested a degree of cross‐protection, against HPV types 31 and 45, which are phylogenetically related to types 16 and 18. If confirmed, this would significantly increase the level of protection afforded by the vaccines.There are still a number of questions to which we do not have answers. We do not know at present how long the immunity conferred by these vaccines lasts: ideally, such a vaccine would be administered with other childhood vaccines, removing any link with sexual activity in the minds of parents. However, that would depend on the immunity lasting for decades, or boosters being given. At present, it is envisaged that the age group between 11 and 12 is probably going to be the target, and indeed, this is what has been recommended in the US. But should we not vaccinate boys as well as girls?If we eliminate cancer due to HPV types 16 and 18, will other types take their place? Will we need different vaccines for different populations? What might be the effect of a vaccine in HIV positive women? There are no answers to these questions at present.A fundamental issue underpinning the potential resistance to an HPV vaccine is the lack of education of both the public and health professionals about HPV. Possibly the most important aspect will be how the information is presented, and work needs to be done to ascertain the most effective ways of doing this. This has been a woefully neglected aspect of strategies proposed for the introduction both of HPV testing and vaccines.In theory, an HPV vaccine could prevent almost all cervical cancer, eventually removing the need for cervical smears. However, there is at least one whole generation of women for whom the vaccine will come too late, and who will continue to require screening. Also, until the number of HPV types in the vaccine is increased, there will still be cancers not prevented by vaccination. The exact point at which vaccination supersedes screening will depend upon the percentage of cancers preventable by the vaccine, the percentage being prevented by the screening programme in place, the attitude of women to having smears and the attitude of the society in which they live to vaccination against a sexually transmitted virus. It is therefore clear this will vary considerably.

HPV genotypes in CIN 2‐3 lesions and cervical cancer: A population‐based study

The distribution of human papillomavirus (HPV) varies between countries and continents leading to different effectiveness of upcoming prophylactic HPV vaccines. This study analyses the HPV distribution in CIN 2-3, recurrent CIN 2-3 and cervical cancer in Iceland. About 80% of incident cases with CIN 2-3 lesions in 1990 and 1999, 99% of cancer cases in 1990-1994 and 1999-2003, and cases with recurrent CIN 2-3 after conization in 1990 were tested with PCR analysis for the presence of 12 oncogenic HPV types. About 95% of the CIN 2-3 and 92% of the cancer cases tested positive for the included HPV types. HPV 16 was the most frequent type followed by HPV 33, 31, 52, 35, 18, 58, 56, 39, 45, 59 in CIN 2-3 and by HPV 18, 33 45, 31, 39, 52, 35, 51, 56 in cancer. HPV 16 and 18 were associated with a significantly increased cancer risk and HPV 52 and 31 with decreased cancer risk compared to the risk of CIN 3. The HPV distribution differed between histological cancer types, stages and age groups. The number of HPV types was not a significant predictor of cancer. Oncogenic HPV types were found in all persistent or recurrent CIN 2-3 disease after conization. Vaccination against HPV 16/18 is estimated to achieve a minimum 40% reduced rate of CIN 2-3 and a minimum 60% reduced cancer rate. This rate could, however, be increased to 95% and 92% respectively by including all the 12 HPV types tested for in this study.

Human Papillomavirus Infections With Multiple Types and Risk of Cervical Neoplasia

Although particular human papillomavirus (HPV) genotypes have been implicated in the origin of cervical cancer, little is known about whether multiple-type HPV infections influence the risk of cervical lesions. Coinfection with multiple HPV types reportedly is more frequent in younger women and those with cytologic abnormalities or impaired immune responses. The planned use of HPV testing in programs screening for cervical cancer makes this issue especially important. The investigators sought an association between multiple HPV types and cervical lesions in 2113 Brazilian women taking part in a study of the natural history of HPVs and cervical neoplasms. Cervical specimens were typed by the polymerase chain reaction technique. Use of a repeated measurement design allowed assessment of the relationship between concurrent and cumulative numbers of HPV types and both any-grade squamous intraepithelial lesions (SILs) and high-grade SIL (HSIL). The mean follow up was 40 months and the mean number of visits was 7.4. Between 1.9% and 3.2% of women at any given visit were infected by multiple HPVs. The cumulative rate of infection by multiple types of HPV in the first year and the first 4 years of follow up, respectively, were 12.3% and 22.3%. The risk of HSIL increased markedly with the number of HPV types. Odds ratios were 41.5 (95% confidence interval [CI], 5.3-323.2) for single-type infections; 91.7 (95% CI, 11.6-728.1) for infection by 2 or 3 HPV types; and 424.0 (95% CI, 31.8-5651.8) for infection by 4 to 6 types, all compared with women who remained HPV-negative during the first year of follow up. Excess risk levels persisted after excluding women infected by HPV-16, those with high-risk types of HPV, and those with persistent infections. The risk level was especially high for coinfections by HPV-16 and HPV-58. The risk of HSIL appeared to be substantially greater for women infected by 4 to 6 HPV types compared with those having 2 to 3 types or single-type infection. These findings suggest a synergistic effect of infection by multiple HPV types on cervical carcinogenesis. It seems likely that HPV typing will increasingly become a part of clinical practice. Also, with the advent of HPV vaccination, HPV testing may prove useful in following immunized persons.

Imiquimod Treatment of Anal Intraepithelial Neoplasia in HIV-Positive Men

To evaluate the treatment of anal intraepithelial neoplasia (AIN) with the local immune response modifier imiquimod in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). Prospective, nonrandomized, open-label pilot study, with a mean follow-up time of 9(1/2) months. Dermatology department of a university hospital. Patients Twenty-eight consecutive HIV-positive MSM with histologically confirmed perianal (n = 23) or intra-anal (n = 5) AIN. Intervention Overnight treatment with self-applied imiquimod cream (perianal AIN) or suppositories (intra-anal AIN) 3 times a week for 16 weeks. Response to treatment was documented using clinical, cytologic, and histologic criteria. Human papillomavirus (HPV) typing and HPV DNA load determination for the high-risk HPV types 16, 18, 31, and 33 were performed. Seventeen (61%) of all 28 patients included in the study and 17 (77%) of the 22 patients with AIN, who applied imiquimod as instructed, showed clinical and histologic clearance at the end of therapy. Four patients had residual AIN and 1 patient did not improve. Clinical response was accompanied by a sharp decline in HPV DNA loads and by a reduction in the number of HPV types, but long-term HPV clearance was rarely achieved. In the follow-up period, AIN cleared in 3 patients with residual AIN. Fourteen (78%) of 18 imiquimod responders with at least 5 five months of follow-up had a normal cytologic and clinical picture at the end of the follow-up period. Three primary responders developed a recurrence. In 6 noncompliant patients, there was no clinical or morphological improvement and the HPV DNA loads remained high. Imiquimod appears to be a safe and effective treatment option for AIN in HIV-positive MSM. Clinical response is accompanied by a significant decrease in high-risk HPV DNA load. These results should encourage controlled randomized studies of imiquimod treatment of AIN.

Failure to demonstrate human papillomavirus (HPV) involvement in Bowen's disease of the skin.

To assess the role of human papillomavirus (HPV) in the aetiology of extragenital Bowen's disease (EBD), a series of 91 cases were analysed using in situ hybridization (ISH) with whole genomic DNA probes of HPV types 1, 2, 4, 6, 7, 11, 12, 15, 16, 18, 26, 36, 37, 39, 42, 55 and 59. No HPV DNA was found in any of the samples tested. A polymerase chain reaction (PCR) was also used to analyse 37 of the 91 samples, using both the consensus primers MY09/MY11 which amplify a large number of HPV types from the L1 region and the degenerate primers CP65/CP70, which amplify the complete set of epidermodysplasia verruciformis (EV) HPV types. All the cases were also negative in the PCR. The results suggest that EBD is not HPV-related, at least in immunocompetent patients.

Detection of Human Papillomavirus DNA by AffiProbe HPV-DNA Test Kit in Cervical Scrapes or Biopsies-Histopathologic Correlates

Objective: The aim of this study was to evaluate and compare the efficacy of punch biopsies and cervical scrapes in the detection of human papillomavirus (HPV) DNA from the cervix and compare the results with the histopathologic diagnosis. Methods: The specimens were collected simultaneously, and HPV DNA was detected using a liquid hybridization test. Results: Biopsies and scrapes were equally efficient, but each detected only two-thirds of all HPV-DNA-positive patients. Thus, the positivity rate increased when both tests were used. Overall, 13% of patients with normal histopathology, 38% of patients with benign atypia, and 66% of patients with squamous intraepithelial lesions (SIL) were HPV-DNA positive. HPV-DNA 16 was found in 54% of HPV-DNA-positive patients with SIL, in 20% of HPV-DNA-positive patients with atypia, and in none of patients with normal histopathology. Conclusions: The liquid hybridization test used in this study detects HPV DNA equally efficiently from both biopsies and scrapes. The test can be performed in 1 working day. However, the sensitivity of the test is low, and it only detects a limited number of HPV types.