Cervical and anal HPV infections in HIV positive women and men

The goal of this review is to summarize recently published epidemiological information that contribute to understanding the natural history of cervical and human papillomavirus (HPV) infection and their associated lesions among human immunodeficiency virus (HIV) infected women and men. HIV-positive women and men are more likely to be infected with oncogenic HPV types and to have cervical intraepithelial neoplasia (CIN) or anal intraepithelial neoplasia (AIN), lesions that may lead to invasive cervical and anal cancer, respectively. Although the magnitude of the increased risk of cervical or anal cancer in HIV-positive individuals is not clear, it is clear that the risk will remain elevated even in the HAART era. Full screening for CIN remains necessary in HIV-positive women and it is likely that screening for AIN will be beneficial as well to prevent invasive anogenital cancer in long-term AIDS survivors.     

High rate of multiple genital HPV infections detected by DNA hybridization.

Cervical smears collected from 450 patients involved in a clinical follow-up of cervical human papillomaviruses (HPV) infections were screened for the presence of HPV 6b, 11, 16, and 18 DNA by both dot blot and southern blot hybridization methods. Using very high stringency hybridization assays, the four HPV types could be easily distinguished by dot blotting. After a preliminary clinical sorting, 42.9% of the samples were found to be HPV-positive. Among the samples infected by a single HPV, type 16 was the most frequent (25.4% of the positive samples) followed by 6b (19.7%), 11 (8.3%), and 18 (7.2%). Double or even multiple infections by the different HPV types were detected at a very high rate (39.4% of the positive samples).     

HPV、CMV与老年男性慢性前列腺炎的关系研究

目的 探究老年慢性前列腺炎患者前列腺液中人乳头状瘤病毒(Human papillomavirus,HPV)、巨细胞病毒(Cytomegalovims,CMV)与前列腺液白细胞计数、卵磷脂小体计数及血清细胞因子关系,为临床治疗提供指导.方法 选取来我院住院治疗的老年慢性前列腺炎Ⅲ型患者87例作为研究对象,同时选取同一时间来我院体检的健康老年人37例作为对照组,经我院伦理委员会审核通过,征求患者或家属同意.血清中IL-2、IL-4、IL-8、TNF-α水平采用酶联免疫吸附实验进行检测,前列腺液中白细胞计数及卵磷脂小体计数通过常规镜检分析.解脲尿原体(UU)、沙眼衣原体(CT)、人类乳头瘤状病毒(HPV)、巨细胞病毒(CMV)采用特异性PCR检测.结果 在白细胞计数上,ⅢA、ⅢB组显著高于正常组(P＜0.01);在卵磷脂小体计数上,ⅢA、ⅢB组显著低于正常组(P＜0.01);老年慢性前列腺炎前列腺液中均发现UU、CT、HPV及CMV,白细胞计数与人类乳头瘤状病毒总型阳性率存在显著正相关(P＜0.01),卵磷脂小体计数与人类乳头瘤状病毒总型阳性率存在显著负相关(P＜0.01);与正常组相比,UU组、CT组、HPV组、CMV组在IL-2、IL4、IL-8、TNF-α上存在统计学差异(P＜0.05).结论 HPV、CMV可能参与老年慢性前列腺炎致病过程,HPV与慢性前列腺炎的炎症程度关系密切.     

Smoking increases oral HPV persistence among men: 7-year follow-up study

Persistent high-risk human papillomavirus (HR-HPV) infection is the key event in the progression of HPV lesions, and more data are urgently needed on asymptomatic oral HPV infections in men. Asymptomatic fathers-to-be (n?=?131, mean age 28.9 years) were enrolled in the cohort, sampled by serial oral scrapings at baseline and at 2-month, 6-month, 12-month, 24-month, 36-month, and 7-year follow-up visits to accomplish persistent and cleared HPV infections. HPV genotyping was performed using nested PCR and Multimetrix® assay. Covariates of persistent and cleared oral HPV infections were analysed using generalised estimating equation (GEE) and Poisson regression. Altogether, 17 HPV genotypes were detected in male oral mucosa point prevalence, varying from 15.1 % to 31.1 %. Genotype-specific HPV persistence was detected in 18/129 men the mean persistence time ranging from 6.0 to 30.7 months. History of genital warts decreased (p?=?0.0001; OR?=?0.41, 95 % CI 0.33?0.51) and smoking increased (p?=?0.033, OR?=?1.92, 95 % CI 1.05?3.50) the risk of persistent species 7/9 HPV infections. Of the 74 HPV-positive men, 71.6 % cleared their infection actuarial and crude clearance times, varying between 1.4 and 79.6 months. No independent predictors were identified for species 7/9 clearance. At the last follow-up-visit, 50.1 % of the fathers had oral mucosal changes, correlating only with smoking (p?=?0.046). To conclude, most of the persisting oral infections in males were caused by HPV16. Smoking increased while previous genital warts decreased oral HR-HPV persistence. No predictors of HR-HPV clearance were disclosed.     

HPV infections and tonsillar carcinoma

Since human papillomavirus (HPV) was first linked to laryngeal/oral carcinomas in 1983, several studies have confirmed its causal role in a subgroup of upper aerodigestive tract tumours. Of the non-genital cancers, tonsillar carcinomas (TCs) have the strongest association with HPV. By the end of 2002, 432 TCs had been analysed for HPV DNA. Overall detection rate was 51%, with HPV-16 being the most prevalent (84%). The original proposal that HPV-33 would be the most frequent HPV in TCs has not been confirmed, being present in only 4.6% of cases. HPV copy numbers are similar to those found in genital carcinomas (10-300 copies/cell), although HPV is mainly episomal in TC. The importance of this observation is unclear, although a role for subepithelial proliferative lymphatic tissue has been speculated. Patients with HPV-16 positive tumours have better overall and disease specific survival than HPV negative patients. They are also younger and the association with conventional risk factors-smoking and drinking-is less significant than in HPV negative patients. Thus, recent data suggest a distinct pattern for HPV-16 positive TCs.     

HPV infections and lung cancer

Because of the major clinical impact of bronchial cancer worldwide, the possibility that human papillomavirus (HPV) contributes to its pathogenesis as a co-carcinogen is an intriguing one. Bronchial squamous cell carcinoma develops through well defined precursor lesions, often at the sites of squamous metaplasia. Benign squamous cell papillomas are rare but HPV DNA has been found in almost half of those studied, implicating a causal association. In invasive bronchial cancer, morphological changes seen in HPV lesions elsewhere are often seen. HPV DNA has been detected in 21.7% of the 2,468 bronchial carcinomas analysed to date and the same high risk types implicated in other squamous cell cancers have been identified. Clearly, more effort should be focused on assessing the role of HPV in bronchial carcinogenesis, by analysing the synergistic effects of carcinogenic agents (cigarette smoke, radiation, asbestos, etc) and HPV in different experimental settings.     

HPV infections and oesophageal cancer

The first reports suggesting an involvement of human papillomavirus (HPV) in the development of both benign and malignant squamous cell tumours of the oesophagus date back to 1982. Since then, a substantial amount of literature has accumulated on this subject, summarised in this review. To date, 239 oesophageal squamous cell papillomas have been analysed in 29 separate studies using different HPV detection methods, with HPV being detected in 51 (21.3%) cases. Many more squamous cell carcinomas have been analysed: of the 1485 squamous cell carcinomas analysed by in situ hybridisation, 22.9% were positive for HPV DNA, as were 15.2% of the 2020 cases tested by the polymerase chain reaction. In addition, evidence derived from large scale serological studies, animal experiments, and in vitro studies is discussed in the light of the highly variable geographical incidence rates of oesophageal carcinoma worldwide. It may be that the (multifactorial) aetiology of oesophageal cancer differs greatly between those geographical areas with a low risk and those with a high risk for this disease. Oncogenic HPV types seem to play an important causal role, particularly in high risk areas.     

Increased IL-18 levels in seminal plasma of infertile men with genital tract infections

PROBLEM: Interleukin (IL)-18 is a novel cytokine, previously known as interferon (IFN)-gamma inducing factor. We evaluated the levels of IL-18 and IFN-gamma in seminal plasma (SP) of fertile and infertile men. METHOD OF STUDY: Semen samples were obtained by masturbation from 80 men, and were examined for the levels of IL-18 and IFN-gamma by enzyme-linked immunosorbent assay. Seven groups were included: (i) fertile men (n = 18), (i) infertile men with genital tract infections (n = 17), (iii) with varicocele (n = 15), (iv) with Klinefelter syndrome (n = 6), (v) with cryptorchidism (n = 7), (vi) with mumps orchitis (n = 7), and (vii) with idiopathic testicular lesions (n = 10). RESULTS: Mean levels of IL-18 were higher in SP from infertile men with genital tract infections compared with SP from other groups except Klinefelter syndrome (P < 0.05). However, no significant differences could be detected for IFN-gamma. A significant positive correlations was found between IL-18 and IFN-gamma in total patient population (P < 0.001). Moreover, a negative correlation was observed between IL-18 and sperm concentrations, and motility (P < 0.01 and < 0.03, respectively). Furthermore, there was a positive and statistically significant association between IL-18 and IFN-gamma levels in SP of infertile men with genital tract infections (P < 0.0001). However, there was no relationship between IL-18 and IFN-gamma, and semen parameters in the same group. CONCLUSION: SP IL-18 levels were increased in men with urogenital infections. Thus, the elevated expression of IL-18 in SP may be used as a diagnostic marker in the male genital tract infections.     

Self-disclosure and its relationship to marital intimacy

Examined the relationship between marital intimacy and self-disclosure from a multidimensional framework within a sample of 10 clinical and 10 nonclinical married couples. The linear combination of various parameters of self-disclosing behavior was able to account for 71.7% (R = 0.853) of the variance in intimacy ratings derived from a structured interview. Results are discussed in terms of both the role that self-disclosure plays in the development of marital intimacy and its therapeutic benefits and limitations in marital therapy.     

Epidemiology of human papillomavirus (HPV) infections and their associations with genital squamous cell cancer. Review article

Reliable assessment of the epidemiology of genital HPV infections is hamphered by a number of technical problems. Because of the lack of tissue-culture systems, methods based on morphological approaches (colposcopy, cytology and histopathology) play a central role in HPV diagnosis. Even DNA-hybridization techniques and the recently introduced DNA amplification with PCR are extremely difficult to standardize, and are thus subject to major interlaboratory variation. Further confusion in the field is created by the complex biological behaviour of HPV infections. As established by the long-term prospective follow-up study of over 500 women which has been running in Kuopio since 1981, clinical progression and regression are significantly related to the grade of the lesion at the time of diagnosis (p less than 0.00001, and p = 0.0005, respectively), as well as to the type of HPV (p = 0.0012). Most importantly, however, genital HPV infections seem to run an extremely fluctuating course, passage from manifest to subclinical or latent infection being frequently encountered in individual patients when examined at 6-month intervals over prolonged periods. This explains the significantly divergent prevalence figures reported in different series (ranging from 2% to 80%), which are completely dependent on the technique used to analyse the presence of HPV, i.e. whether a) PAP smear, b) biopsy, c) DNA hybridization, or d) PCR amplification. The first two are capable of disclosing only manifest (clinical) infections, the latter two also the latent ones. In an unselected population of 22-year-old Finnish females, the prevalence of clinical HPV infections was about 3 per cent, and the adjusted annual incidence was 8.0 per cent. According to estimates of the life-time risk, up to 79% of Finnish females will contract at least one HPV infection between the ages 20 to 79 years. When related to the long-term trends in invasive cervical cancer in Finland, it is evident that this 79% life-time risk of becoming HPV-infected or even the observed 15% clinical progression rate for HPV infections in the prospective follow-up study by no means signifies an identical risk of developing cervical cancer (i.e. 0.79 x 0.15 = 11%). It seems likely that in countries where mass-screening programmes exist (and precancer lesions are traced), the high prevalence of HPV infections is not necessarily reflected as an increased prevalence of invasive cervical carcinomas. The distinction of lesions at risk for malignant transformation from those regressing spontaneously will have major implications in therapeutic considerations of genital HPV infections.     

Prevalence of genital HPV infections in a regularly screened population in The Netherlands in relation to cervical cytology

To determine the prevalence of human papilloma virus (HPV) genotypes in relation to cervical cytology, 1,290 cervical samples from a regularly screened population of 30-55-year-old women were investigated. Gynaecological specimens, obtained from the cervix, were cytologically classified and screened for the presence of HPVs 6/11 and 16/18 using dot-spot DNA hybridisation. Of the cervical samples containing unequivocally normal cells, 21 of 1,271 (1.6%) were found positive for HPV, and of the cervical samples containing cells with mild dysplasia, 6 of 14 (43%) were found positive for HPV. All five samples containing cells consistent with severe dysplasia or carcinoma in situ were found positive for HPV. Approximately 50% of the HPV-positive samples contained HPV 16 and/or HPV 18 DNA.     

The uganda study on HPV variants and genital cancers.

BACKGROUND: Genital cancers in Uganda have been the most frequently diagnosed cancer in men as well as in women since the 1950s. Genetic studies have detected HPV-16 variants of Af1 class and identified a new sub-class designated Af1-u. OBJECTIVES: The main goal of this study is to analyze the prevalence of HPV strains and HPV variants in anogenital lesions of Ugandan male and female subjects in order to possibly determine their role in the pathogenesis of such lesions and to develop an Ugandan preventive HPV vaccine program. STUDY DESIGN: The study is planning to enroll male and female subjects affected by genital lesions, in particular to collect 200 scrapes/biopsies from women with normal ectocervical epithelium as well as with all different degrees of ectocervical lesions (from CIN 1/LSIL to cervical carcinoma). All samples are analyzed by PCR amplification of the L1 conserved region (nt 6584-7035) and the E6/E7 genes (nt 34-880), nucleotide sequence analysis, homology and phylogenetic studies. Variant distribution studies will be followed by serological studies of prevalence and incidence in 1000 women. PRELIMINARY RESULTS AND CONCLUSIONS: Penile cancers from the Kyadondo County have been analyzed for the presence of HPV sequences. More recently 16 ectocervical scrapes and three biopsies have been received from women attending the Nsambya Hospital and analyzed for the presence and type of HPVs. Our results, obtained by PCR and sequencing analysis, allowed the identification of HPV-16 Af1 sequences in 100% of tumor tissue and in 6.25% of scrapes. HPV 45 was identified only in one tumor together with HPV 16 infection. HPV 33 and HPV 58 were present in 20% and 40%, respectively of HPV positive benign samples. The results are showing a narrowing of the HPV pattern in more advanced lesions, suggesting that mainly HPV-16 Af1 patients are progressing to cancer.     

Two novel genital human papillomavirus (HPV) types, HPV68 and HPV70, related to the potentially oncogenic HPV39.

The genomes of two novel human papillomavirus (HPV) types, HPV68 and HPV70, were cloned from a low-grade cervical intraepithelial neoplasia and a vulvar papilloma, respectively, and partially sequenced. Both types are related to HPV39, a potentially oncogenic virus. HPV68 and HPV70 were also detected in genital intraepithelial neoplasia from three patients and one patient, respectively. Comparison with sequence data in the literature indicates that the subgenomic ME180-HPV DNA fragment, cloned from a carcinoma cell line, corresponds to an HPV68 subtype and that several HPV DNA fragments amplified by PCR from genital neoplasia represent worldwide distributed variants of HPV68 and HPV70.     

Natural history of oral papillomavirus infections in spouses: a prospective Finnish HPV Family Study.

BACKGROUND: The natural history of genital human papillomavirus infection is well known, but nearly nothing is known about the outcome of oral HPV-infection. OBJECTIVES AND STUDY DESIGN: To study natural history of oral HPV in spouses during the follow-up 331 women (mean 25.5+/-3.4 years) and 131 men (mean 28.8+/-5.0 years) were recruited from maternity unit. Scrapings from healthy oral mucosa of spouses at baseline, 2, 6, 12 and 24 months and genital samples were taken for HPV testing. HPV DNA was detected by nested PCR and confirmed by hybridization using a cocktail of 12 high-risk (HR) oligoprobes. RESULTS: The detection rate of HR HPVs varied from 15% to 27%. Baseline oral HPV status between the spouses was closely related (odds ratio 4.3; 95% confidence interval 1.6-12.0; P=0.006). Persistent oral infection in one spouse was a significant risk factor (odds ratio 10.0; 95% confidence interval 1.5-68.7; P=0.005) for oral HR HPV persistence in the other partner. Cumulative incidence of new HR HPV infections was identical in both spouses, while men seemed to clear their infection more rapidly. In univariate survival analysis, the partner's oral or genital HPV status, oral sex habits or age did not predict clearance or acquisition of oral HR HPV. CONCLUSION: Natural history of HPV infection in oral mucosa mimics that of genital HPV infection. Oral sex had no association to oral HPV infection, but a persistent oral HPV infection of the spouse increased the risk of persistent oral HPV infection 10-fold in the other spouse.     

HPV infections in benign and malignant sinonasal lesions

This review updates the evidence that the human papillomavirus (HPV) is involved in the development of benign and malignant sinonasal lesions. Since the early 1980s, when evidence was provided on the possible involvement of HPV in the aetiology of both benign respiratory papillomas and squamous cell carcinomas, a substantial number of studies have explored this issue. To date, 33.3% of sinonasal papillomas and 21.7% of sinonasal carcinomas analysed have been shown to be positive for HPV. Many elements of the data parallel the observations made in HPV lesions at other mucosal sites, such as malignant transformation and frequent recurrence after radical treatment; the fact that low risk HPV types 6 and 11 are usually confined to benign lesions, whereas the reverse is true for the oncogenic HPV types 16 and 18; and the presence of squamo-columnar junctions and squamous cell metaplasia in the sinonasal system. The discrepancies reported by several studies might result in part from technical reasons, but it is also possible that sinonasal lesions have a heterogeneous aetiology (HPV related and non-related) and/or that some novel (yet unidentified) HPV types exist in these lesions, which are detected by some studies but not by others.     

A prospective study of antibody responses to defined epitopes of human papillomavirus (HPV) type 16 in relationship to genital and anorectal presence of HPV DNA.

The aim of this study was to investigate whether antibody responses against synthetic peptides derived from genital human papillomavirus (HPV) proteins are associated with laboratory-proven genital and anorectal HPV infection. In this study, 158 heterosexual patients (110 women and 48 men) were followed prospectively. At each visit we collected serum samples as well as specimens from several sites in the anogenital area for detection of HPV type 6/11 (HPV-6/11), -16, -18, and -33 DNAs by PCR. Immunoglobulin A (IgA) and IgG responses against disrupted bovine papilloma virions and eight different synthetic peptides derived from HPV-6/11, -16, and -18 were determined for serum samples from the first and the last visits. The subjects attended the Municipal Sexually Transmitted Disease Clinic in Amsterdam, The Netherlands, two to seven times (mean, four times) at approximately 4-month intervals. Women were monitored over a period of 155 person-years, and men were monitored over 65 person-years. The magnitudes of the IgA responses against HPV-16 late protein epitopes L1:13, L1:31, and L2:49 were significantly higher in the sera from the last visit among the currently HPV DNA-positive participants than in HPV DNA-negative persons (P = 0.02). When the persons positive for any HPV type at any time during the follow-up period were compared with those who were negative at all times during the follow-up period, we also found a significant elevation of IgA responses against L1:31 and L2:49 (P = 0.04 and 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Isolation ofBacteroides ureolyticus from the genital tract of men with and without non-conococcal urethritis

Urethral specimens from 247 heterosexual men — 118 patients with non-gonococcal urethritis and 129 controls with no evidence of urethritis — were examined for the presence ofBacteroides ureolyticus. Bacteroides ureolyticus was isolat-ed from 45 (34.9 %) of the controls and from 31 (26.3 %) of the urethritis patients; there was no significant difference between these rates (p=0.1). There was no association between the density ofBacteroides ureolyticus on primary isolation plates in either group.