Human papillomavirus.

In the past year, new data have been published on the molecular biology of human papillomavirus infections and their relationship to cervical neoplasia. As molecular techniques have become more sophisticated and as the molecular knowledge of human papilloma-virus infections has been pursued in greater depth, it is increasingly apparent that this human tumor DNA virus is similar to a number of other oncogenic DNA viruses that have been described and well studied. These viruses appear to act through a common pathway of producing oncogenic proteins that interfere with key signalling elements that normally control the process of cell division. With a better mechanistic knowledge, it should be possible to design new therapeutic approaches to treating human papillomavirus-associated disease that are directed toward specific cellular events such as turning off the production of E6 and E7 proteins or restoring the activity of pRB or p53. Increased attention has also been turned to immunologic aspects of HPV infections, and a number of groups are eagerly pursuing the possibility of using simple office-based procedures to detect specific proteins encoded for by the human papillomavirus open reading frames in an attempt to determine who has been infected, is actively infected, and has proteins being produced that are indicative of neoplasia. From the clinical point of view, the use of outpatient excisional techniques such as the loop electrosurgical excision procedure is rapidly supplanting ablative techniques because of their superior ability to identify early invasive carcinomas and adenocarcinomas in situ that have not been detected by colposcopy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Subclinical vulvar papillomavirus infection.

Eighty-eight cases of subclinical human papillomavirus (HPV) vulvar infection were detected in a consecutive colposcopic series of 968 women. Three patterns of acetowhite lesions had a 72% predictive value (88/122) for histologically assessed HPV. The prevalence of subclinical vulvar HPV in self-referred patients was 7.9% (73/918); it was 9% (88/968) in the overall series and significantly higher in younger patients (age less than 25 years: 21/106, or 19.8%) or in those with cervical HPV or cervical intraepithelial neoplasia (CIN) (40/100, or 40%). Routine inspection of the vulva after acetic acid lavage in association with a Papanicolaou test might help identify Papanicolaou-test-negative patients at high risk of developing cervical HPV or CIN. Treatment with beta-interferon (2,000,000 IU daily intramuscularly for 10 days) was given to 30 consecutive patients, but the results were poor: regression was observed in only 2 cases.     

Molecular epidemiology of human papillomavirus.

Human papillomavirus (HPV) has been considered to be an etiologic factor for anogenital cancers, such as cervical cancer and possibly a subset of cancers of the aerodigestive tract. These small, non-enveloped, double-stranded DNA viruses primarily infect the epithelium and induce benign as well as malignant lesions of the mucosa and skin. Some HPVs are considered to be high-risk due to their strong implication in carcinogenesis, particularly the malignant progression of cervical tumors. The recognition of papillomaviruses as a major etiologic agent for human cancers has increased their medical importance and stimulated research into developing strategies for the screening, diagnosis, prevention and treatment of HPV-associated diseases.     

Human papillomavirus infection and cervical ectopy.

OBJECTIVES: To investigate the prevalence of human papillomavirus (HPV), and HPV type 16 (HPV16) infection in cervical ectopy, and the presence of anti-HPV16 secretory IgA (sIgA) antibodies. METHODS: DNA from patients with cervical ectopy (n=218), HPV-associated lesions (n=111), and controls without evidence of cervical ectopy or HPV infection (n=93) were analyzed by PCR for the presence of HPV and HPV16. The presence of mucosal sIgA antibodies against HPV16 capsid antigens (VLP) was assayed in cervical mucus by ELISA. RESULTS: Prevalence of HPV DNA was higher in cervical ectopy than in controls (P=0.04; OR=2.06; 95% CI 0.99-4.33). HPV16 was 6.3 times more prevalent in cervical ectopy than in controls. Anti-HPV16 sIgA were detected more frequently in cervical ectopy patients than in controls (P=0.0004). CONCLUSIONS: Cervical ectopy correlates with HPV infection. HPV16 is highly prevalent in cervical ectopy. sIgA antibodies against HPV16 capsids are generated in patients with cervical ectopy.     

Immunosuppression and human genital papillomavirus infection.

A group of 39 patients who underwent iatrogenic immunosuppression for renal transplant were evaluated by means of colposcopic, cytologic, and histologic investigations. Evidence of human papillomavirus (HPV) infection was found in 30.7%, more frequently in the cervix. Biopsy specimens of the most atypical areas showed the presence of cervical intra-epithelial neoplasia in one case. The high incidence of HPV infection in this group suggests that immunodeficient patients should have close monitoring of the entire ano-genital tract.     

Genital human papillomavirus infection. A growing concern

HPV infections of the genital tract are one of the most common sexually transmitted viral infections in the United States. Data from STD clinics and private physicians' offices reveal that genital warts, one manifestation of genital HPV infection, have been diagnosed more frequently in recent years. Using a variety of diagnostic techniques, asymptomatic HPV infection has been identified in men and women and is probably much more common than clinically apparent infection.     

Subclinical manifestations of vulvar human papillomavirus infection.

We studied the presence of human papillomavirus (HPV) DNA by in situ hybridization in 74 colposcopically defined subclinical vulvar lesions obtained from 51 patients (mean age 25 years, range 18-42 years) referred for atypical Papanicolaou smears to the Colposcopy Clinic. Serial sections of formalin-fixed, paraffin-embedded biopsy tissue were stained by routine hematoxylin and eosin stain or were separately hybridized with biotin-labeled probes of HPV types 6, 11, 16, and 18 at high stringency and with mixed HPV probes at low stringency. Histologic evidence of HPV infection (koilocytosis or dysplasia) was found in eight lesions. Overall, 10 lesions were positive by in situ hybridization with HPV DNA. Although certain colposcopic features were more strongly associated with HPV DNA than others were, we were unable to demonstrate any consistent correlation between HPV DNA positivity or specific HPV DNA types and colposcopic categories. There was little correlation between HPV DNA positivity and the histopathologic incidence of HPV infection and dysplasia. Three of the 10 hybridization-positive lesions were severely dysplastic as compared with 0 of 64 nonhybridizing lesions. In spite of this association between HPV DNA and dysplasia, HPV DNA hybridization added no additional clinically relevant information to the histopathologic findings. We emphasize the significance of careful colposcopic examination of the vulva with directed biopsies.     

Human papillomavirus

Human papillomaviruses are ancient small DNA viruses and represent the most common sexually transmitted infection in the world. In the majority, HPV infection is cleared by an incompletely understood immune response. HPV is a necessary but not sufficient cause of cervical cancer, and responsible for a proportion of other anogenital cancers including vulval, vaginal, anal and oropharyngeal. Oncogenesis is likely mediated through viral proteins which hijack host-cell machinery in epithelial keratinocytes and disrupt host tumour-suppressor proteins. Much work has been undertaken to further characterise the natural history of HPV infection and cervical disease. Such efforts have been translated to important public health interventions like the introduction of HPV tests in cervical screening. HPV vaccination programmes are expected to further reduce the incidence of high-risk HPV infections and resultantly HPV-related disease.     

Cervix uteri and human papillomavirus infections. Current approach

The incidence of genital warts among sexually active young people is growing, but the association of human papillomavirus with abnormal cervical smears is not clear. The development of Cervical Intraepithelial Neoplasia (CIN) may be expected within one year by one third of patients with histologically documented viral cytopathic effects. The presence of HPV infection in colposcopically normal cervical tissue both inside and outside the transformation zone may help to explain why current methods for treatment of cervical HPV infection are often unsuccessful. A significant proportion of the male population is infected in countries were HPV is an important factor in cervical carcinogenesis. Patients may be considered cured when cytology and colposcopy are found to be negative in two subsequent examinations. At the moment we simply do not know whether or not HPV causes cervical cancer. Perhaps shortly we will be able to write with greater certainty.     

Human papillomavirus in lesions of anogenital mammary-like glands.

Long considered as ectopic breast tissue, anogenital mammary-like glands (MLGs) have recently been suggested to represent distinctive structures located in the anogenital area. We studied 16 neoplasms of anogenital MLG for human papillomavirus (HPV) DNA using INNO-line probe assay (LiPA) HPV Genotyping kit, GP5+/6+, CP(SGB), and FAP 6085-6319 primer sets. The lesions included 3 fibroadenomas, 2 adenosis tumors, 1 invasive ductal carcinoma, 1 tubulolobular carcinoma, 2 hidradenoma papilliferum with prominent cystic change rendering a cystadenoma appearance and oxyphilic metaplasia, and 7 cases of extramammary Paget disease. All 3 fibroadenomas, both adenosis tumors, both hidradenoma papilliferum, and the tubulolobular carcinoma proved negative for HPV DNA. HPV-31 was detected by LiPA in the case of invasive ductal carcinoma. In 2 of the 7 patients with extramammary Paget disease, there was HPV DNA present in the lesional tissue, typed as HPV-6 (LiPA) and a type which was closely related to HPV-21 and HPV-24 (FAP 6085-6319), whereas the remaining 5 cases tested negative. These results coupled with those obtained from literature review suggest that HPV plays no causative role in lesions of anogenital MLG.     

Human papillomavirus and the pathogenesis of vulvar carcinoma.

The pathogenesis of vulvar and cervical cancer are thought to be similar and to be related to a sexually transmitted agent, which, in recent years, has been demonstrated to be human papillomavirus. These two neoplasms differ dramatically in age distribution and relationship to precursor lesions, making a common etiology unlikely. The apparent discrepancies can be explained by a hypothesis that implicates human papillomavirus as an etiologic factor for the majority of cervical carcinomas but for only a small proportion of vulvar carcinomas. Most vulvar carcinomas occur in older women and are not related to human papillomavirus, whereas a subset of vulvar carcinomas occur in young women and are related to this virus. Characterization of two distinct types of vulvar carcinoma may clarify associated risk factors and may have important implications in the clinical management of this disease.     

Expression of cytokeratin No. 19 polypeptide in genital papillomavirus lesions.

A series of 23 punch biopsies proved to contain human papillomavirus (HPV) type 16 and with established clinical course (including HPV-NCIN, HPV-CIN I, and HPV-CIN II lesion), and 18 additional biopsies of HPV 6-, 11-, 16- or 18-induced genital lesions were analyzed immunohistochemically for expression of cytokeratin No. 19 polypeptide. An immunoperoxidase-ABC technique was used with a polyclonal antibody raised against a synthetic nonapeptide corresponding to the residues 2-10 of the NH2-end, non-alpha-helical region. This polyclonal cytokeratin No. 19 antibody stained mainly (but not exclusively) the basal cells of the normal exocervical epithelium (heterogeneous pattern). Basal cell staining was intense slightly more frequently in HPV-CIN than HPV-NCIN lesions, i.e., ++ or more in 14/24 (58.3%) versus 8/17 (47.0%), respectively. The difference was more marked in the staining of the superficial cells, 70.8 and 58.8% showing intense expression of cytokeratin No. 19, respectively. In 6 (21.4%) of the 28 HPV 16 lesions, basal cell layer was intensely stained, as contrasted to none of the 13 HPV 6, 11 or 18 lesions. The most distinct feature was the well-defined granular staining pattern of the superficial layer in 8 out of 10 HPV 6/11 lesions, as contrasted to the homogeneous pattern in 24 out of 28 HPV-16-infected lesions. In superficial cells, regressed lesions exhibited intense staining in 9/13 (69.2%), as compared with only 4/10 (40%) of the progressed lesions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Education about human papillomavirus and human papillomavirus vaccines in adolescents

PURPOSE OF REVIEW: The purpose of this article is to review recent literature that may help guide the development of effective, evidence-based strategies to educate adolescents about human papillomavirus (HPV) and HPV vaccines. Educational strategies are essential, given several new and highly effective technologies to prevent HPV and related diseases such as cervical cancer. RECENT FINDINGS: Although little has been published regarding adolescent knowledge about HPV and HPV vaccines, studies conducted primarily in adult women demonstrate that knowledge generally is poor. Studies of adolescent attitudes about HPV vaccines have identified several modifiable factors associated with intention and confidence in one's ability to receive the vaccine, including higher perceived severity of cervical cancer and fewer barriers to vaccination. Studies of clinician attitudes about HPV vaccines have demonstrated that although clinicians generally support vaccination, some report concerns; for example, adolescents may practice riskier sexual behaviors after vaccination. Studies also show that clinicians believe that educational materials developed specifically for adolescents are essential. SUMMARY: The recent literature on adolescent knowledge about HPV and attitudes about HPV vaccines supports the importance of designing developmentally appropriate educational materials for adolescents about HPV and HPV vaccines, and provides guidance for the development of key educational messages.     

Human papillomavirus screening for women with atypical Papanicolaou smears.

A study was undertaken to evaluate the utility of human papillomavirus (HPV) DNA screening and colposcopy in the management of women whose Papanicolaou smears demonstrated atypia less than dysplasia. Fifty patients whose initial Papanicolaou smears were interpreted as showing atypia less than dysplasia were evaluated for the presence of HPV 16 DNA in exfoliated cervicovaginal cells and for histologic findings on biopsy. Those 50 patients were compared to two groups of patients: one consisting of 124 patients with biopsy-documented cervical intraepithelial neoplasia (CIN) and another of 112 patients with normal Papanicolaou smears. The presence of HPV 16 DNA was confirmed with Southern analysis in 46% of patients with atypical Papanicolaou smears, 46% with confirmed CIN and 11.6% with normal Papanicolaou smears. The 50 patients with atypical smears underwent colposcopically directed cervical biopsies, revealing the following results: 14 (28%) had normal histology, 29 (58%) had koilocytosis without dysplasia, and 7 (14%) had CIN. HPV 16 DNA was present in exfoliated cervicovaginal cells from a large percentage of patients from each category (50% of patients with normal histology, 41.2% with koilocytosis and 57% with CIN). HPV 16 DNA screening did not predict which patients with atypical smears had underlying CIN. Colposcopically directed biopsy remains the evaluation method of choice.     

生殖道人乳头瘤病毒感染规范诊治

女性生殖道人乳头瘤病毒(HPV)感染很普遍,其中多数HPV感染能自然清除。有众多的HPV检测方法,但HPV检测的主要目的是确定是否存在高级别癌前病变, 而不是诊断有无HPV感染。对生殖道低危型HPV感染的治疗以清除疣体为主,对单纯高危型HPV感染需规范管理,对生殖道高级别癌前病变应及时治疗。