Human Papilloma Virus Natural Cures

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Papillomavirus infection and cervical cancer

Papillomaviruses are a group of small DNA tumor viruses that are known to induce a broad range of benign and malignant epithelial lesions in the infected host (for a review, see ref. 1). Ofthe over 100 human papillomavirus types (HPVs) that have been identified to date, approx 25-30 are associated with lesions of the anogenital tract. Depending on the likelihood of associated lesions to progress to malignancy or to remain benign, genital-tract-associated HPVs are further classified as high- vs low-risk HPVs. High-risk HPVs such as HPV16 or HPV18 are strongly associated with cervical cancer irrespective of other risk factors and geographic location (2). Cervical cancer is the second most common cancer in women worldwide, causing 15 of female cancer mortality (3). Approximately 400,000 new cases of invasive cancer are diagnosed each year with 5-yr survival ranging from 44 to 66 for all clinical stages (4). Over 97 of cervical cancers contain high-risk HPV DNA and express the viral...

Papillomaviridae A Taxon Separate from the Polyomaviruses

Traditionally, papillomaviruses had been placed with the polyomaviruses such as the simian virus 40 (SV40) in the family papovaviridae based on the properties that could be observed in the 1970s, namely, electronmicroscopically similar viral capsids that lack envelopes and double-stranded circular DNA genomes. Research during the 1980s revealed that polyoma- and papillomaviruses have different genome sizes (5kb vs. 8kb) and different genome organizations, since early and late genes face one another in the polyomaviruses but are oriented in the same direction in the papillomavirues. Lastly, there are no homologies between the proteins of papilloma- and polyomaviruses, with the exception of a small domain in the E1 gene and the T-antigen gene, respectively (Clertant and Seif, 1984), which is associated with the helicase activity of these proteins. While it was therefore obvious since the mid-1980s that papillomaviruses and polyomaviruses are unrelated and should be considered as two...

Papillomavirus Structure and Assembly

Papillomaviruses are spherical, nonenveloped DNA viruses 55-60 nm in diameter. Their coat or capsid is comprised of 72 pentamers (capsomeres) of their major capsid protein (L1) arranged on a T 7 icosahedral lattice. An internal minor (in amount) capsid protein (L2) is associated with a subset of the L1 pentamers that forms the outer shell. Enclosed within the capsid shell is the viral genomic DNA packaged as a minichromosome by cellular nucleosomes. The overall structure of the papillomavirus virion is strikingly similar to that of the polyomaviruses, where VP1 is the major capsid protein comprising the pentameric capsomeres, and the VP2 and VP3 proteins are analogous to L2. The structures of papilloma and polyoma viruses have been a longstanding object of investigation, and have served to model the study of other icosahedral viruses. Their symmetry provided support for the Crick-Watson postulate (Crick and Watson, 1956) that most viruses likely would have structures constructed of...

Papanicolaou Pap smear 363

Pap smear See Papanicolaou (pap) smear. Pap smear screening The need for rigorous surveillance in HIV infection has given rise to the argument for routine Pap smear screening in HIVpositive women. At the time of screening, it is equally important to examine the vulva and vagina, culture the cervix for STDS (gonorrhea and chlamydia), and diagnose and treat any vaginitis present, including atrophic vaginitis. Management strategies also include liberal referrals for colposcopic evaluation, particularly for vulvar and vaginal lesions that cannot be definitively diagnosed, so that colposcopically directed biopsies can be obtained. Most clinicians feel that pap smear screening should be performed every six months for the majority of HIV-positive women. It is equally important to utilize a cytology laboratory that is consistently accurate and that uses the 1988 Bethesda system for reporting. Using this system, all Pap smears with recurrent atypias, cervical intraepithelial neoplasias of all...

Human Papillomavirus E6 Proteins 10221 HPV E6 and p53

Most studies on thehuman papillomavirus E6 proteins have focused on thehigh-risk HPV types associated with human cervical cancer. The first activity identified for the high-risk HPV E6 proteins was the ability to form a complex with p53 (Werness et al., 1990), a property not shared with the low-risk HPV E6 proteins. Through this interaction, high-risk E6 can block the ability of p53 to transcriptionally activate p53-responsive promoters (Mietz et al., 1992). The steady state levels of p53 are generally quite low in HPV-positive carcinoma cell lines and in cells immortalized by the HPV oncoproteins (Scheffner et al., 1991). The observation that E6 proteins of high-risk HPV types 16 and 18 promote the ubiquitin-dependent degradation of the p53 protein in vitro (Scheffner et al., 1990) led to the hypothesis that E6-mediated ubiquitylation of p53 and its subsequent degradation accounted for the low steady-state levels of p53 in cells. Indeed, the half-life of p53 is dramatically decreased...

Papillomavirus Species

The Most Frequently Studied Papillomavirus Types, Their Biological and Clinical Properties, and Phylogenetic Associations on the Level Of Genus and Species as Recently Recognized by the International Council on the Taxonomy of Viruses (ICTV) Table 3.2. The Most Frequently Studied Papillomavirus Types, Their Biological and Clinical Properties, and Phylogenetic Associations on the Level Of Genus and Species as Recently Recognized by the International Council on the Taxonomy of Viruses (ICTV) Family papillomaviruses (papillomaviridae) Alpha-papillomaviruses Common skin warts, frequently in genital warts of children Benign mucosal lesions HPV-6 and HPV-11 in male and female genital warts, condylomata acuminata of cervix, laryngeal papillomas some of these lesions can progress malignantly Beta-papillomaviruses papillomaviruses Delta-papillomaviruses Bovine papillomavirus-1 (BPV-1) (selected from a type-rich genus) Kappa-papillomaviruses Cottontail rabbit papillomavirus (CRPV)...

The 1930s and 1940s Biology of the Shope Papillomavirus and Other Animal Papillomaviruses

Papillomaviruses were the second class of viruses, after retroviruses, shown to induce malignant tumors (Shope, 1933). As such, the Shope papillomavirus, which is now designated the cottontail rabbit papillomavirus (CRPV), became an important experimental model of viral tumorigenesis. Not only did infectious extracts induce benign papillomas in cottontail and domestic rabbits, but some of the benign lesions progressed to squamous cell cancers, the first demonstration that a mammalian virus could cause a malignant solid tumor (Rous and Beard, 1935 Syverton, 1952 Syverton and Berry, 1935). It was also found that some papillomas regressed, while others persisted without progression. A causal relationship between persistence of a papilloma and the risk of malignant progression was inferred, as the carcinoma developed at the site of the papilloma and malignant tumors still expressed viral antigens. In addition, if a lesion regressed, the site of the former lesion was no longer at risk for...

Prospects for Prevention and Treatment

The identification of a human tumor virus immediately suggests strategies for tumor prevention and control. Public heath measures can be instituted to protect the population from exposure or to identify carriers or people at elevated risk of cancer. Successful examples of this approach are the elimination of HBV and HCV from the blood supply and the use of Pap screening to identify women with HPV-induced cervical dysplasia. In a more recent example, maternal-to-infant transmission of HTLV-1 is reduced if carrier mothers refrain from breast-feeding (Hino et al., 1997). Another well-established modality to control viral infection is vaccination. An effective hepatitis B vaccine is already reducing the incidence of chronic hepatitis B virus infection and hepatocellular carcinoma (Huang and Lin, 2000), and on the basis of clinical trials demonstrating protection against persistent high-risk HPV infection and the development of precancerous lesions, HPV vaccines were recently approved for...

The 1950s and 1960s Cell Differentiation and Virus Replication

The development of tissue culture techniques in the 1940s and 1950s did not lead to the successful in vitro propagation of papillomaviruses. By contrast, the life-cycle and transforming activity of polyoma virus and SV40 virus, which had been discovered in the late 1950s (Stewart et al., 1958 Sweet and Hilleman, 1960), could be studied in monolayer cultures. The latter viruses, therefore, became the most popular DNA tumor viruses to study, leading to remarkable advances in understanding their molecular biology and impact on cells. Interest in papillo-maviruses waned in the 1950s and 1960s largely because they continued to be less tractable to tissue culture analysis and because human papillomaviruses were not thought to be agents of medically important disease. During this period, papillo-maviruses were classified as belonging to the same virus family as polyoma and SV40 (the papovaviridae), as the papillomavirus capsid and genome were both structurally similar to, but larger than,...

Effects of HPVs on Epithelial Differentiation

Cells exits the cell cycle and migrates away from the basal layer to begin differentiation. The presence of HPV gene products maintains differentiating cells in the cell cycle and blocks the degradation of nuclei (Stubenrauch and Laimins, 1999). Examination of the expression of markers of epithelial cell differentiation such as involucrin, keratin 10, transglutaminase, and filaggrin indicate that HPVs exert modest effects on cell differentiation during the productive stage of the viral life cycle (Ruesch and Laimins, 1998). During the productive life cycle, there is a close correlation between the expression of filaggrin and the induction of late viral functions (Ruesch and Laimins, 1998). HPV-positive cells activate late viral functions in differentiating cells that have re-entered S-phase, and fail to express the intermediate filament associated protein, filaggrin. In contrast, the cells that do not amplify viral DNA nor express late genes remain in G1 and synthesize filaggrin....

Nuclear Localization and DNA Binding of L1 and L2

Like most DNA viruses, both polyoma and papilloma virions are assembled in the cell nucleus. Thus the capsid proteins translated in the cytoplasm must be nuclear imported for virion assembly. For both virus families, it appears that the karyopherin a p importin pathway is used, and that the nuclear localization signal (NLS) sequences are composed of the classical mono- or bipartite basic amino acid domains. These basic domains also seem to serve as DNA binding motifs, with a nonspecific DNA sequence preference. DNA binding is an important feature for the capsid interaction with the viral genome, but the precise structural orientation is unknown. A major difference between the nuclear import of polyoma and papillomavirus capsid proteins appears to be whether the minor proteins (VP2 3, L2) are co- or independently transported with the major capsid proteins. L2 can be independently nuclear localized in the absence of L1 (Florin et al., 2002), whereas the polyoma proteins appear to...

Overview of Viral Transcription in Productive Infections

Early efforts to propagate papillomavirus in conventional cell culture systems comparable to those used for many other mammalian DNA viruses proved unsuccessful (Butel, 1972). Simply put, HPVs are not lytic viruses and no plaque assay exists. To understand this difficulty, two issues were addressed in the 1980s to appreciate the architecture of the host tissues in which the papillomaviruses reproduce and to develop tools to investigate the viral activities in naturally infected human lesions. In situ hybridization assays in thin sections of productively infected patient specimens reveal that the papillomaviral DNA and mRNA are below detection in the basal and parabasal cells but both dramatically increase in abundance in a subset of the spinous cells. The L1 major capsid protein is expressed and virions are assembled in a small number of terminally differentiated superficial cells (Stoler and Broker, 1986 Crum et al., 1988 Stoler et al., 1989, 1992 Higgins et al., 1992 reviewed by...

Organotypic Raft Cultures of Primary Human Keratinocytes as a Model System to Study HPVs

Organotypic or raft cultures of primary human keratinocytes (PHKs) grown at the medium air interface achieve stratification and squamous differentiation in vitro (Asselineux and Prunieras, 1984), suggesting that they may support the productive phase of papillomavirus infection (Broker and Botchan, 1986). Initial efforts with this culture system recapitulated high-grade squamous intraepithelial neoplasia with keratinocytes transfected with recombinant HPV-16 plasmid (McCance et al., 1988). The culture system was then optimized to generate from native primary human keratinocytes a squamous epithelium that closely resembles the native tissues (Wilson et al., 1992), with the exception that the basal cells are actively cycling rather than being quiescent as in native tissues. This culture condition allowed, for the first time, the productive phase of the HPV infection in the outgrowth of explanted condylomatous tissues (Dollard et al., 1992) or, alternatively, in the cell line CIN-612 9E,...

Is There More Than One Way to Replicate Viral DNA

The DNA replication measured in transformed tissue culture cells, such as mouse C127 or NIH 3T3 cells, has the hallmarks of the latent or early stage of the viral life cycle, where early genes are expressed, capsid proteins are not expressed, and the viral DNA is replicated and maintained at a relatively low level (100s of copies). An unanswered question is whether DNA replication required for the much higher copy numbers that are associated with productive infection and generation of new virus particles, proceeds by the same or a different mechanism as DNA replication during latent infection. An early-to-late switch exists for viral gene expression since viral transcripts encoding capsid proteins, absent during latent infection, appear in more superficial layers of the papilloma. The nature of this switch is not understood. Similarly, there are hints of a switch in the mode of DNA replication and it has been proposed that a switch to rolling circle replication may occur at late...

E5 Proteins and Major Histocompatibility Antigen Expression

E5 proteins can impair the expression and activity of major histocompatibility (MHC) antigens. Because these antigens play central roles in antigen presentation and immune recognition, inhibition of MHC expression and function can impair host immune defenses against virally infected cells. Cell surface expression of class I MHC antigens is reduced in cultured cells expressing the E5 proteins of several papillomavirus types (Ashrafi et al., 2005 Ashrafi et al., 2002 Cartin and Alonso, 2003 Marchetti et al., 2002). The HPV16 E5 protein down-regulates cell surface expression of HLA-A and HLA-B (Ashrafi et al., 2005), which present viral peptides to cytotoxic T lymphocytes (CTLs). Thus, the E5 protein may allow HPV-infected cells to avoid CTL-mediated killing. In contrast, non-classical HLA-C and HLA-E were not down-regulated by the E5 protein, which may allow the cells to escape natural killer (NK) cells as well. Reduced cell surface expression of MHC antigens in E5-expressing cells...

HPV E7 and Chromosomal Instability

Multipolar mitoses are a distinguishing feature of high-risk HPV-positive cancers (Winkler et al., 1984). Such abnormal mitotic processes can lead to asymmetrical chromosome segregation, thereby contributing to the induction of aneuploidy. The characteristic multipolar mitoses in cervical lesions are caused by supernumerary centrosomes, and the high-risk HPV E6 and E7 proteins cooperate to generate these defects (Duensing et al., 2000). In contrast, cells expressing low-risk HPV E6 E7 proteins do not exhibit centrosome abnormalities. Centrosome abnormalities also arise in cervical cancers (Balsitis et al., 2003 Reznikoff et al., 1994) and skin lesions that develop in HPV-16 E6- and or E7-expressing transgenic mice (Schaeffer et al., 2004).

HPVIndependent Effects of the E2 Protein

In addition to the effects described above that require HPV repression, E2 proteins can also exert HPV-independent effects. E2 expression can induce apoptosis or perturbation of the cell cycle in HPV-negative cells, and E2 mutants defective for DNA binding can elicit HPV-independent effects in HPV-positive cells. For example, delivery of the HPV31 E2 gene on an adenovirus vector caused normal foreskin keratinocytes to arrest in S-phase with ongoing cellular DNA replication, resulting in the generation of cells with greater than 4N DNA content and, eventually, the induction of apoptosis (Frattini et al., 1997). The HPV18 and BPV1 E2 proteins expressed from adenovirus vectors induced rapid p53-independent apoptosis in the absence of E2 DNA binding in HPV-positive or HPV-negative cells, effects which appeared to require high-level E2 expression (Desaintes et al., 1997, 1999). Expression of an ectopic HPV16 E2 gene by induction from a metallothionein promoter by treatment with heavy...

The 1970s to the Early 1990s Viral Genetics and the Emergence of HPV as a Medically Important Virus

Molecular cloning and related techniques developed in the mid-1970s partially overcame the experimental limitations to studying papillomaviruses, leading to renewed interest in these viruses and to a wealth of new information about them. During the late 1970s and early 1980s, papillomavirus research followed two main themes experimentally oriented studies of animal papillomaviruses, especially BPV1, and more clinically oriented studies of HPVs. By the second half of the 1980s, clinical and experimental aspects of HPVs became predominant, following the recognition of their medical importance. primary cell cultures (Black et al., 1963 Thomas et al., 1964), BPV1 was found to induce morphologic transformation and focus formation of established tissue culture cell lines, such as the mouse C127 and NIH 3T3 cell lines (Dvoretzky et al., 1980). In contrast, CRPV and the HPVs known in 1980 did not display this activity. The ability of BPV1 to transform cultured nonepithelial cells is related...

Pathogenicity Versus Latency

Infections with PVs are clearly the cause of common and genital warts and a central causal factor in the etiology of cervical cancer. While this concept is well confirmed, it is nevertheless erroneous to characterize PVs as aggressive neoplastic agents. Among the arguments for this statement is the observation of a huge number of HPV types in the skin of asymptomatic individuals (Antonsson et al., 2000, 2003 Antonsson and Hansson, 2002) and the wide variety of HPV types in healthy individuals that give rise to epidermodysplasia in high-risk patients (Steger et al., 1990 de Villiers, 1989). Even the so-called high-risk HPV types such as HPV-16 most often give rise to neoplasia only in the context of the transformation zone of the cervix, while they lead to subclinical infection elsewhere, for example throughout the vagina and at penile epithelia. All of these Antonsson, A., Forslund, O., Ekberg, H., Sterner, G, and Hansson, B.G. (2000). The ubiquity and impressive genomic diversity of...

Structure Determination

Electron microscopy and image analysis of negatively stained SV40, polyoma, and papillomaviruses (Klug, 1965 Anderer et al., 1967 Finch and Klug, 1965) established that the virion capsids were comprised of subunits (capsomeres) arranged in an icosahedral lattice (Fig. 5.1). The T, or triangulation, number nomenclature was derived by Caspar and Klug to explain the possible icosa-hedral symmetries of capsids of various sizes (Caspar and Klug, 1962). Strict icosahedral symmetry implies 60 x T identical copies of the capsid subunits. In a T 7 capsid, 60 x 7 or 420 identical subunits should be present, with 12 pentamers of these subunits at the pentavalent positions and 60 hexamers at the hexavalent positions (T 1 capsids have 60 subunits, or 12 pentamers, all located at pentavalent positions). Unexpectedly, when Rayment et al. (1982) analyzed low-resolution (25 A) images of polyoma virions, only pentamers (72 pentamer or 360 subunits) were identified (Fig. 5.2). This architecture was...

Pentamer Pentamer Contacts

Schematic showing the bonding interactions modeled by Modis et al. (2002) in the complete T 7 papilloma virion. A The threefold pentamer-pentamer interactions observed in the T1 structure on the left and the possible C-terminal arm conformation at the same threefold location in a T7 particle. B The invading C-terminal arms of adjacent pentamers wrapping around their neighboring pentamers allowing important juxtaposition of cysteine residues (e.g., cys428 HPV16L1) for disulfide bond formation. (See Plate 4). Figure 5.6. Schematic showing the bonding interactions modeled by Modis et al. (2002) in the complete T 7 papilloma virion. A The threefold pentamer-pentamer interactions observed in the T1 structure on the left and the possible C-terminal arm conformation at the same threefold location in a T7 particle. B The invading C-terminal arms of adjacent pentamers wrapping around their neighboring pentamers allowing important juxtaposition of cysteine residues (e.g., cys428...

Human Tumor Viruses

Despite these difficulties, six viruses are now widely recognized as playing an etiologic role in human cancers. Four of these viruses, human papillomaviruses (HPV), Epstein-Barr virus (EBV), hepatitis B virus (HBV), and human herpesvirus-8 (HHV-8), contain DNA genomes, and the remaining two, human T lymphotropic virus 1 (HTLV-1) and hepatitis C virus (HCV), contain RNA genomes. 1.3.1. Human Papillomaviruses The HPVs are small, non-enveloped DNA viruses that cause benign epithelial papillomas or warts in their natural hosts, with particular HPV types causing specific types of papillomas or lesions at particular anatomic sites. The main medical importance of the HPVs is the causal role played by certain high-risk HPV types, primarily HPV16 and HPV18, in a variety of carcinomas. The most important and best documented HPV-associated cancer is cervical carcinoma (Durst et al., 1983 Bosch and Munoz, 2002), but HPV is also thought to play an etiologic role in other anogenital cancers, skin...


Bauknecht, T., Jundt, F., Herr, I., Oehler, T., Delius, H., Shi, Y., Angel, P., and Zur Hausen, H. (1995). A switch region determines the cell type-specific positive or negative action of YY1 on the activity of the human papillomavirus type 18 promoter. J. Virol. 69 1-12. Be, X., Hong, Y., Wei, J., Androphy, E.J., Chen, J.J., and Baleja, J.D. (2001). Solution structure determination and mutational analysis of the papillomavirus E6 interacting peptide of E6AP. Biochemistry 40 1293-1299. Bedell, M.A., Hudson, J.B., Golub, T.R., Turyk, M.E., Hosken, M., Wilbanks, G.D., and Laimins, L.A. (1991). Amplification of human papillomavirus genomes in vitro is dependent on epithelial differentiation. J. Virol. 65 2254-2260. Beger, M., Butz, K., Denk, C., Williams, T., Hurst, H.C., and Hoppe-Seyler, F. (2001). Expression pattern of AP-2 transcription factors in cervical cancer cells and analysis of their influence on human papillomavirus oncogene transcription. J. Mol. Med. 79 314-320. Brandsma,...

Disulfide Bonds

The formation of disulfide bonds is critical for stable papilloma capsid assembly. L1 from HPV virions isolated from skin lesions is cross-linked by disulfide bonds (Doorbar and Gallimore, 1987). Sapp (Sapp et al., 1995) first demonstrated that dithiothreitol (DTT) treatment caused disassembly of L1 VLPs into capsomeres. When purified intact virons (BPV) are treated with DTT, there is no disassembly but rather a conformational change resulting in expansion of the capsids by approximately 10 percent in diameter (Li et al., 1998). This expansion allows penetration of proteases and nucleases to the interior, which can then result in virion disruption. This structural change may correspond to the open capsids seen by cryoEM (Belnap et al., 1996). In vitro assembly of capsids from recombinant pentamers (HPV11) is promoted by oxidation of cysteine

Role of L2

For polyoma, the inside appearance of the virion has been deduced by subtracting 25A resolution structures of complete virions against empty VP1 capsids (Griffith et al., 1992). The resulting image, which should represent all of the non-VP1 density including the genome, shows 72 prongs of electron density extending from the virus core to the axial cavities of the VP1 pentamers. These prongs were identified as VP2 and VP3, and were interpreted as bridging the genome to the outer capsid shell. The VP1 DNA binding domain is immediately C-terminal to its VP2 3 interaction domain, similar to the configuration found for L1 with L2 suggesting a related conformation. Therefore it might be anticipated that L2 could form similar bridges in the papilloma virion as VP2 3 for polyoma.


Atomic structure data are now available for both polyoma and papilloma capsids. Despite the lack of primary sequence homology between VP1 and L1 capsid proteins, the overall conformation of the capsomeres and capsid are remarkably similar. C-terminal domain strand invasion appears to be a general principle in linking pentamers on the T 7 lattice, although L1 and VP1 utilize different bonding partners and connectors. Self-assembly in vitro and in recombinant systems also appears to be robust for both VP1 and L1. The biologic controls of assembly must harness the intrinsic self-assembly properties of the capsid proteins such that encapsidation occurs only around the genome. Cellular chaperones and viral-encoded proteins with specific DNA binding properties likely play a role in solving these problems. papillomavirus genomes in Saccharomyces cerevisiae. J. Virol. 76 3350-3358. Baker, T.S., Drak, J., and Bina, M. (1989). The capsid of small papova viruses contains 72 pentameric capsomeres...

Anal intraepithelial neoplasia

Anal intraepithelial neoplasia Also called anal neoplasia (AIN). AIN is an abnormal cell growth, a lesion, of the anus that may develop into cancer. The term neoplasia itself does not mean cancer. It is an abnormality that is benign or malignant. It is known that AIN is more prevalent in people who have been exposed to the human papillomavirus (HPV), both men and women. It also occurs more often in women and gay males than in heterosexual men. HpVs includes more than one hundred distinct types of viruses. Not all of the types are thought to have links to particular abnormalities in tissue. people who have been exposed to HpV or have had anal or cervical warts should consider having at least an annual anal cytology test. This test is similar to a cervical screening in women. Swabs are taken of anal tissue and sent to a lab for examination. Although this is currently not an official screening protocol, because of lack of government guidelines, the rates and similarities between cervical...

Sarah S Williams Bruce J Aronow PhD and Susanne I Wells PhD

Papillomavirus Infection and Cervical Cancer E2 Inhibition of Cellular Growth Cellular Senescence E2 Expression and Senescence in HPV-Positive Cervical Cancer Cells Infection with the high-risk types of human papillomavirus is strongly linked to the development of cancers of the uterine cervix. Carcinogenesis depends on the continuous expression of the viral E6 and E7 oncogenes in the affected individual. Transcription of these oncogenes can be negatively regulated by the viral E2 protein. Carcinogenic progression of human papillomavirus (HPV)-positive lesions is accompanied by the integration of the viral DNA into the cellular genome and the disruption of the viral E2 open reading frame. When reintroduced into HPV-positive cancer cells, E2 proteins suppress cellular growth through senescence induction. E2 repression of E6 E7 is necessary and sufficient for this process, indicating that important senescence mediators must be inhibited by the viral oncoproteins for both the initiation...

E2 inhibition of cellular growth

The papillomavirus E2 protein is a regulatory factor with multiple roles in the transcription and replication of the viral DNA (67,68). E2 proteins resemble prototypical transcription factors, with an N-terminal transcriptional activation domain and a C-terminal DNA binding domain, separated from each other by a less conserved hinge region. E2 proteins from all viral strains form dimers and interact sequence-specifically with a palindromic motif ACCG(N)4CGGT, where the affinity of the natural E2-binding sites is modulated by the nature of the (N)4 spacer and where the underlined nucleotides are preferred (69-73). The bovine papillomavirus (BPV) E2 proteins have been studied most extensively. Distinct BPV E2 proteins have been detected in BPV-transformed C127 cells. The largest 48-kDa form, E2-TA, represents the product of the complete open reading frame. A short internally initiated 30-kDa form of BPV E2, known as E2-TR, is devoid Several experimental observations suggest that the...

E2 expression and senescence in hpvpositive cervical cancer cells

Expression of BPV1 or HPV16 full-length E2 protein in HPV-positive cervical cancer cells results in either apoptotic cell death or senescence. Apoptosis and senescence take place in different subsets of E2-expressing cells and are controlled by distinct pathways. Apoptosis is observed within 24 h after E2 expression and requires neither E2 DNA-binding nor E2 transcriptional activity (91,92,94). Apoptosis is independent of E6 E7 promoter repression, as it occurs in HPV-positive and HPV-negative cell lines and is mediated at least, in part, via direct interactions between specific residues in the E2 transcriptional activation domain and cellular apoptotic regulators (91-94). In contrast to the timing and mechanism of E2 apoptosis, senescence induction occurs at later times in HPV-positive cell lines such as HPV18-positive HeLa and HPV16-positive Caski cells as well as human keratinocytes immortalized with HPV16 genomic DNA (96,112,113). Senescence is not observed in HPV-negative U2OS...

Transcriptional profiling of senescing cervical cancer cells

In an effort to explore in detail the molecular consequences of E2 expression in HeLa cells and to identify regulators and markers of senescence in this system, we have monitored global transcriptional changes associated with sensescence in HPV-positive, E2-expressing HeLa cells using high-density oligonucleotide microarrays (118). An early timepoint was chosen to examine transcriptional changes in initial stages ofthe senescence

Antagonistic aspects of senescence and immortality

A window of gene expression changes during E2-mediated senescence induction. Expression of E2 in HPV-positive cells causes senescence via the repression of the viral E6 E7 oncogenes. Several gene groups that are regulated during senescence induction were categorized according to biological processes that they are known to regulate. An asterisk marks induced genes. All others are repressed genes. (Modified from ref. 118.) Fig. 3. A window of gene expression changes during E2-mediated senescence induction. Expression of E2 in HPV-positive cells causes senescence via the repression of the viral E6 E7 oncogenes. Several gene groups that are regulated during senescence induction were categorized according to biological processes that they are known to regulate. An asterisk marks induced genes. All others are repressed genes. (Modified from ref. 118.)

Regulation of p53 function

It was demonstrated some years ago that human papilloma viruses (HPV), especially HPV 16, 18 and also some other types, are associated with high-grade cervical intraepithelial neoplasia (CIN) and invasive cervical squamous carcinomas. The integration of these viruses in the genome results in increased expression of the proteins known as E6 and E7, and these proteins have the ability to transform cells into the neoplastic state. Immunohistochemical studies have shown co-localisation of p53 phosphoprotein and E6, suggesting an association between them (Liang et al., 1993). It would appear that the E6 protein binds the p53 phosphoprotein (Werness et al, 1990). This requires another cellular factor called the E6-associated protein (E6-AP). This event leads to a rapid degradation of p53 protein, mediated by ubiquitin-dependent proteolysis (Huibregtse etal., 1993). The introduction of a single HPV16-E6 gene causes the immortalisation of cells and sharply reduces p53 protein levels (Band et...

Central nervous system lymphoma See primary

Cervical cancer Malignant neoplasm (growth) in the cervix, or neck of the uterus. Cervical cancer may occur at any age from puberty on. The mortality rate increases with age. Risk factors include early age at first intercourse, multiple sexual partners, more than five pregnancies, and a history of syphilis or gonorrhea. Women whose mothers took DES while pregnant are also at risk. It is suspected that an oncogenic factor, most probably a virus, is transmitted sexually, and the human papilloma virus is thought to be an important factor.

Retinoblastoma susceptibility gene rb abnormalities in cancer

Consistent with these thoughts is the observation by Wrede et al. (1991) that no abnormalities of rb or p53 are detectable in human papilloma virus (HPV> positive cervical carcinoma cell lines. The rb protein expressed in these cell lines was of the wild-type (Scheffner et al., 1991), but evidence of abnormalities are found in HPV-negative cell lines. Riou et al. (1992) found that early-stage invasive cervical cancers which over-express the myc oncogene in the absence of HPV show a high risk of distant metastases, thus myc gene over-expression may be deemed as an independent prognostic indicator of metastasis.

Regulation of cell cycle progression by retinoblastomasusceptibilitygene product

The sequestration of unphosphorylated rb protein will allow the cells to transit into the S-phase. It is known that functional rb protein forms stable complexes with transforming oncoproteins such as those encoded by the simian virus 40 (SV40) and human papilloma viruses (Templeton et al, 1991). HPV E7 binds to rb protein and such binding is necessary for E7 protein to immortalise and transform cells (Dyson et al., 1989 Munger et al, 1989 Gage et al, 1990). The SV40 T-antigen is known to bind preferentially to the underphosphorylated rb protein (Ludlow et al., 1989). Although these studies suggest a close correlation between phosphorylation and the transition of cells from G, into the S-phase of the cell cycle, phosphorylation might be a progressive event and this may be reflected in the molecular heterogeneity found in rb proteins (Xu et al., 1989). The process of rb phosphorylation may be an incremental process beginning in late G,, several hours before transition into the S-phase

Rash on the Soles of the Feet

His past medical history is significant for HIV, which was diagnosed 24 years earlier, idiopathic thrombocytopenic purpura resulting in a splenectomy 16 years earlier, and bipolar disorder diagnosed 18 years earlier with a suicide attempt 5 years ago. He has been on intermittent HAART therapy and his infectious disease history is positive for hepatitis B, gonorrhea, HPV (human papilloma virus) with anal warts, and herpes simplex virus 1 and 2. His most recent PPD skin test (purified protein derivative) for tuberculosis was negative.

Lowgrade squamous intraepithelial lesion LSIL

Abnormalities in the cells on the surface of the cervix an aberration that turns up on Pap tests. LSILs have a slightly higher degree of abnormality than do atypical squamous cells of undetermined significance (ASCUS). Three approaches to managing this abnormality include colposcopy (a procedure in which the clinician examines the cervix through a lighted, binocular-like magnifying instrument and biopsies abnormal areas), watchful waiting (repeating the Pap test every six months), and testing the cells in the smear for the strains of human papilloma virus (HPV). See atypical squamous CELLS OF UNDETERMINED SIGNIFICANCE and HIGH-GRADE SQUAMOUS INTRAEPITHELIAL LESION.

Why Consider A Career In Obstetricsgynecology

Despite its seemingly specialized nature, obstetrics and gynecology provide much diversity and variety. Medical students should disregard the narrow views of colleagues who may dismiss these specialists as pap smear providers by day and baby delivery service by night. The breadth of issues includes acute and chronic medical conditions, health maintenance, genetics, operative gynecology, pregnancy

OV Statin See nystatin

Sure to high levels of radiation may also cause ovarian cancer. The most common type of ovarian cancer is the epithelial carcinoma in the ovary's outer layer. Frequently there are no symptoms in the early stages of ovarian cancer, making it difficult to obtain an early diagnosis, when there is the greatest chance for effective treatment. An ovarian tumor can grow for some time before pressure or pain can be felt or other problems are noticed. When symptoms do occur, they may include abdominal swelling or bloating, discomfort in the lower part of the abdomen, a full feeling after a light meal, lack of appetite, nausea, vomiting, gas, indigestion, weight loss, constant need to urinate, diarrhea, or constipation, and nonmenstrual bleeding. procedures used in the diagnosis and evaluation of ovarian cancer may include an internal exam of the uterus, vagina, ovaries, fallopian tubes, bladder, and rectum, a pap smear, ultrasound, blood and urine tests, and x rays. Additional procedures that...

Justification For Using Cell Culture And In Vitro Assays

The purpose of short-term in vitro genotoxicity assays is to predict if a chemical may have a potential to cause cancer and to offer information regarding chemical mechanisms of DNA damage. These tests do not prove that something causes cancer, nor is there one single test that provides an unequivocal ruling that a given substance is a carcinogen. A carcinogen is generally accepted as an agent that induces neoplasms in humans or animals, increases the incidence of tumors, or speeds up the time for tumor development. Cancer is currently the second leading cause of death in the United States after heart disease. Established human carcinogens include physical agents such as UV light 35 , x-radiation, and gamma radiation 36 , infectious agents such as hepatitis B and C viruses 37 , human papilloma viruses 38 , and helicobacter pylori bacterium 39 , and many chemical agents including alcohol 40 , aflatoxin 41 , Cr6+ 42 , and polycyclic aromatic hydrocarbons 43 .

Safe sex and good sex See bad sex

Safer sex A term sometimes preferred to safe sex, because it does not imply that sexual contact can be made 100 percent safe. The term recognizes the likelihood of human error, the inexactness of human knowledge, and the fact that people will engage in activities that may not be 100 percent safe. Latex, polyurethane, or other plastic barriers for oral and anal-oral sex between lesbians and gay men are often recommended by safer sex educators. These educators note that lesbians are definitely at risk for HIV and other sexually transmitted diseases because exchange of bodily fluids and possibly blood is often involved in lesbian sex. Viruses such as herpes simplex and human papillomavirus (which causes genital warts) can be transmitted by oral-genital contact, which is considered a medium to low risk on the spectrum of HIV transmission. Several different products can be used by lesbians as barriers for oral sex. Unlubricated latex condoms can be cut into flat barriers by cutting off the...

Sexually transmitted disease 447

At the minimum, these diseases cause discomfort. Left untreated, some STDs can cause serious long-term health problems. For example, gonorrhea and chlamydial infections can cause pelvic inflammatory disease, infertility, and ectopic pregnancy. Several common STDs adversely affect pregnancy, resulting in spontaneous abortion, stillbirth, and premature delivery. Genital infections due to human papillomavirus are associated with cervical cancer, one of the most common cancers in women throughout the world today. Moreover a pregnant woman can pass an infection to her baby. Infections in newborns include syphilis, herpes, gonococcal conjunctivitis (an eye disease that can lead to blindness), and chlamydial pneumonia, an infection of the lungs that can develop into a chronic respiratory disease.

Shaken baby syndrome 451

STDs include gonorrhea, syphilis, chancroid, scabies, herpes, genital warts, pubic lice, trichomoniasis, genital candidiasis, hepatitis B, nonspecific Health problems caused by STDs tend to be more severe and more common among girls and women, partly because girls may not have symptoms and thus do not seek care until serious problems occur. Some STDs can spread into the uterus and fallopian tubes, causing pelvic inflammatory disease, which in turn is a major cause of infertility and tubal pregnancy. STDs in girls and woman also may be eventually associated with cervical cancer. For example, human papillomavirus infection causes genital warts and cervical cancer.

Novel pathways regulated during e2 senescence

Little is known about the molecular machinery triggering the cellular senescence decision and execution, but a multitude of cellular pathways is likely involved. The above analysis revealed a number of novel candidate gene groups, two of which are depicted in Fig. 3 and discussed here. Coordinate induction of six members and regulators of the Ras-related RAB family of small GTPases, RAB2, 5B, 13, 31, RAB interacting factor and the RAB geranylgeranyltransferase a-subunit might reflect or perhaps even functionally relate to the senescence phenotype. RAB GTPases are highly conserved regulators of fluid-phase and receptor-mediated endocytosis, transport between intracellular compartments, and exocytosis (for review, see ref. 124). Membrane association of RAB proteins is mediated by C-terminal geranylgeranyl anchors, and RAB protein function is exerted through interactions with specific effectors at individual transport steps. Consistent with the specific localization of RABs, such as RAB2...

Prevention and Health Screening

An analysis of pooled NHIS data on Latina women for 1990 and 1992 provided estimates of cancer screening rates for Latino subgroups (Zambrana et al. 1999). According to this study, the proportion of women aged 18 and older who reported having had a Pap smear in the past 3 years ranged from 72 in Mexican women to 80 in Mexican American women. Seventy-three percent of Cuban women and 77 of Puerto Rican women reported having had a Pap smear in the past 3 years, although these rates were still well below the Healthy People 2000 target of greater than 95 (Zambrana et al. 1999). The proportion of women aged 35 and older who reported having had mammography in the past 3 years ranged from 35 in Mexican women to 54 in Mexican American women. The rates for Cuban and Puerto Rican women were 77 and 83 , respectively (Zambrana et al. 1999). The true prevalence of breast and cervical cancer screening may be lower because these estimates were based on telephone survey methods and excluded poorer...

Targeting TLRs with specific ligands

Herpes Genitalis Discharge

Topical imiquimod therapy is used for the treatment of external genital and perianal warts caused by Papilloma virus infection 17 . The FDA has recently approved imiquimod for the treatment of actinic keratoses, and there is mounting evidence that imiquimod is an effective treatment of certain types of skin cancer 47, 48 . Resiquimod is a more potent analogue of imiquimod, and trials are under way to assess its use in treatment of genital herpes and hepatitis C virus 49 .

Differential Diagnosis

Conditions to be considered in the differential diagnosis of breast cancer include mammary dysplasia, fibroadenoma, intraductal papilloma, lipoma, and fat necrosis.2 The diagnosis of breast cancer is based on the examination of tissue or cells obtained by biopsy. The gold standard for diagnosis and prognosis in breast cancer is the TNM staging system established by the American Joint Committee on Cancer and the International Union Against Cancer (T size of the tumor, N extent of regional lymph node involvement, and M presence or absence of distant metastases). The degree of axillary lymph node involvement is the major prognostic indicator for later systemic disease.1 The second factor that predicts disease outcome is tumor size. The majority of breast cancers are histopathologically classified as either (1) ductal, which constitutes approximately 70-80 of breast cancers, or (2) lobular, representing approximately 10 of breast cancers.4 These classifications are further divided into...

Vulvar Intraepithelial Neoplasia

VIN or vulvar squamous dysplasia is a common cause of vulvar burning that is often missed by the health-care provider. VIN is categorized as VIN I (mild dysplasia), VIN II (moderate dysplasia), and VIN III (severe dysplasia, carcinoma in situ) (7). Women with VIN can present clinically with the predominate symptom of vulvar burning (6), which can be intermittent or constant. Women may or may not have a prior documented history of human papilloma virus infection. Frequently, the vulvar examination is normal or there may be unifocal

Vulvar Neoplasm Vulvar Intraepithelial Neoplasia

Imiquimod is currently FDA approved for treatment of genital warts is being used currently to treat human papillomavirus-associated VIN. In a few small noncontrolled studies, topical 5 imiquimod cream three times weekly was found to clear VIN II III (137,148). Studies have shown at least 75 overall response (148). Efficacy, however, may be limited when dysplasia extends into ducts of glands or into hair follicles (138). Invasive carcinoma must be ruled out prior to therapy, as invasive disease has been found after treatment with imiquimod. Further studies investigating efficacy are warranted.


Atypical squamous cells of undetermined significance (ASCUS) Abnormalities in the cells on the surface of the cervix, an aberration that turns up on pap tests. Three approaches to managing this mild abnormality include colposcopy (a procedure in which the clinician examines the cervix through a lighted, binocular-like magnifying instrument and biopsies abnormal areas), watchful waiting (repeating the Pap test every six months), and testing the cells in the smear for the strains of human papilloma virus (HPV) that are associated with progression to cancer. In 1997, the National Cancer Institute launched a nationwide study to evaluate these three approaches. Its two principal purposes are to determine whether watchful waiting is a reasonable alternative to colposcopy (if so, many women would be spared the inconvenience and discomfort of the procedure) and to discern whether HPV testing can predict which types of cells will revert to normal and which will progress to high-grade

Cervical cap

The best way to screen HIV-positive women for cervical cancer has long been a matter of debate. Medical reports through the years have documented that women with HIV have a greater risk of cervical cancer than noninfected women, and that it progresses more rapidly and tends to recur after treatment. The accuracy of the pap smear, the standard method for detecting abnormalities that might develop into cervical cancer, has recently been called into question, particularly in the case of women with HIV. These women frequently have lower genital tract infections that may obscure test results. in colposcopy, a low-power microscope (colposcope) is used to examine the cervix, and if suspect tissue is observed, a biopsy is performed for further evaluation. Colposcopy has traditionally served only as a corroborative test in women with abnormal pap smears, but in recent years some medical authorities have urged that cervical col-poscopy be part of the routine management of HIV-positive women...


Cervical cancer is largely a preventable disease. Screening by Pap smear for all sexually active women can identify those with dysplastic precursor lesions so that they can be treated and monitored before more serious disease develops. With the high rates of HPV infection and dysplasia known to exist in the HIV-infected population, screening, early diagnosis, treatment, and careful monitoring are crucial. With no medical intervention available to prevent HPV infection and disease, regular Pap smears, lower genital tract inspection, and appropriate colposcopic follow-up and treatment of abnormalities are the best hope for preventing serious disease in women with cervical dysplasia. Colposcopy is performed to evaluate atypical and dysplastic smears. At this point, there is not a consensus of opinion regarding optimal frequency of Pap smears or the management of abnormal findings in HIV-positive women. Note that there are a number of methods for destroying or removing dysplasia from the...


Circumcision The surgical removal of the end of the prepuce, of foreskin, of the penis. Circumcision is a social or religious custom, usually performed on newborn babies at the request of the parents. The issue of circumcision as it relates to HIV transmission is hardly trivial. It has been suggested that there is a relationship between absence of circumcision and HIV. Studies seem to support such an association but must be interpreted cautiously because evidence may be unavoidably confounded with other factors. Since the late 1800s, it has repeatedly been found that men with sexually transmitted diseases (STDs) are more likely to be uncircumcised than are men without STDs. Modern investigators have reported that uncircumcised men were more likely than circumcised men to be infected with gonorrhea or syphilis, less likely to have genital warts, and equally likely to have herpesvirus infection. Recently several investigators have reported that uncircumcised men may be more susceptible...


Several hypotheses have been proposed to identify etiological factors for vulvodynia. A high concentration of calcium oxalate crystals in the urine (27), allergies (28), hormonal relationships (29), history of abuse (30), genetics (25), psychological conditions (11), and recurrent infections (e.g., Candidiasis yeast, human papilloma virus, and bacterial vaginosis) (20,31,32) have been thought to play a role in disease development. Yet, there is no agreement in the literature regarding these and other theories. Moreover, these issues have been described primarily in small, uncontrolled studies, and there is a lack of systematic, large-scale studies that explore them in greater depth (33).

Community norms 113

When the centers for disease control and prevention (CDC) began drafting gynecological guidelines for HIV-positive women in 1993, the CDC's advisory group had to choose between a schedule of regular Pap smears and or colposcopy. The agency settled on recommending repeat Pap smears as a way of countering false-negative individual Paps. AIDS activists feared that HIV-positive women who had to wait six months or more for testing of abnormal Paps would risk contracting cervical cancer and insisted on colposcopy examinations for all HIVpositive women. Health care providers and activists generally agree, however, that, as a practical matter, it may be a more effective use of resources to create the best conditions for successful use of the low-tech Pap test than to put them into the more sophisticated colposcopy technique.

Infectious Diseases

So far, many groups have been successful in activating the pathway against viral targets with diverse replication strategies, including HIV (136,152-162), hepatitis B and C (HBV HCV) (163-170), human papilloma virus (HPV) (171-173), polio virus (174,175), herpes virus (176), human T-cell leukemia virus-1 (177), respiratory syncytial virus (178), influenza (179), Epstein-Barr virus (180), and, finally, corona viruses such as SARS (181-185).


Several in vitro studies have already demonstrated the potential use of RNAi in cancer treatment. Cancer cells usually differ from normal cells by their uncontrolled growth and the ability to escape programmed cell death (apoptosis). For nutrition supply, they assemble a network of blood vessels around tumors, and to evade chemotherapy, they might change surface composition. Therefore, targets for a possible RNAi treatment are genes that are either involved in cell division and proliferation such as growth factors, tumor suppressor genes, transcription factors, and apoptosis inhibitors (106,171,202-217) or proto-oncogenes that take part in many regulatory events and signaling cascades such as Ras and Bcl-2 (208), as well as viral oncogenes, such as from human papilloma virus (HPV). Impaired apoptosis signaling is associated with tumor development and confers resistance to chemotherapy and apoptosis triggered by the death receptor pathway (204). In many tumors, antiapoptotic...


A history of genital infections is a risk factor for VVS (34). Early etiologic hypotheses focused on epidemiologic links to vulvovaginal candidiasis and genital human papilloma virus (HPV) infection. One study reported a history of recurrent candidiasis in 80 of VVS cases (35) others found the prevalence of Candida infection to be within the range found in normal subjects (36). The diagnosis of candidiasis in the aforementioned studies was often presumptive hence, early misdiagnosis of VVS as candidiasis could have contributed to the observed statistical linkage. More recent investigations, which corroborated referring physicians' statements or prior laboratory results with patient reports, found VVS risk to be associated with a history of bacterial vaginosis, Candida albicans, pelvic inflammatory disease, trichomoniasis, and vulvar dysplasia (34). The epidemiological association with HPV has been controversial. Studies investigating this hypothesis (most of which examined a limited...

Early stopping

Tion in women include Pap smears, pregnancy counseling, and access of women with HIV infection to clinical trials and investigational treatments. Because HIV-infected individuals experience a range of unique oral conditions in addition to dental problems common to all individuals, both specialized and routine oral care is required by individuals with HIV infection. Similarly, because of the wide range of ocular complications associated with HIV disease, specialized and routine eye examinations are required by individuals with HIV infection.


HIV-positive women who are essentially asymptomatic, with CD4 counts greater than 400, who are not sexually active and who have no new gynecological complaints can be followed with gynecological screening and pap smears annually. Symptomatic women, women with AIDS, and sexually active women should be scheduled for gynecological evaluations, Pap smears, and STD screening every six months. Interval assessment should occur whenever a woman presents with low abdominal pain vaginal or rectal discharge abdominal bloating genital sores new onset of swollen or painful inguinal nodes dysuria, hesi

Human rights

A patient does not have to have had a wart in a particular area to be affected by neoplasia in that region. What this means is that, despite not having genital warts in a particular area, it is still possible to develop CIN or AIN. The clinical course of HPV and anogenital neoplasia is accelerated in HIV-positive patients. HPV infection and neoplasia in HIV-infected patients are often persistent and recurrent, extend to adjacent areas of skin and mucous membranes, resist conventional therapy, and can progress to invasive cancer. Whether women with both HIV and HPV infection will have an accelerated rate of progression to invasive genital tract cancer cannot be predicted. HIV-infected women have a significant increase in cervical abnormalities and a higher prevalence of (CIN). HIV-positive men have higher incidences of AIN and anal cancers than their HIVnegative counterparts. In HIV-positive patients dysplasia and cancerous lesions occur at a younger age, are...


Note that gynecologic problems are common among HIV-positive women and are frequently present at the time of initial evaluation and care. Some gynecologic issues are unrelated to the patient's serologic status, whereas others are directly related to HIV disease and associated with immunosuppression. Still others are associated epi-demiologically with HIV because of common risk factors, such as sexual behavior or substance abuse. To date, breast cancer has not been related to HIV disease, associated with immunosuppres-sion, or associated epidemiologically with HIV. Nonetheless, along with routine gynecologic evaluations, pap smears, STD screening, and sigmoi-doscopy colonoscopy, routine mammography is one of the core components of a sound health maintenance program for women.

Papillary tumor

Papilloma An epithelial tumor of skin or mucous membrane consisting of hypertrophied papillae covered by a layer of epithelium. Papillomas are often found in the genital area. Included in this group are warts, condylomas, and polyps. Most are caused by a strain of the human papilloma virus (hpv). There are more than 40 types of HPV infections. Certain viral strains predispose women to and indeed probably cause cervical, vaginal, and vulval cancer. Women known to have HPV infections need to be monitored carefully with pap smears and at times colposcopy and biopsy. Cryosurgery or laser surgery may be necessary if precancerous changes occur. Male partners of women with HPV infections should be evaluated by a physician familiar with this problem, as HPV infections can be invisible to the naked eye and require special staining techniques and or col-poscopy to evaluate. papillomavirus A virus that causes papillomas or warts in humans and animals. Papillomaviruses belong to the papovavirus...

Parasomnia 383

Applying spermicides with nonoxynol-9 to affected or treated areas may be helpful in reducing transmission of the virus. Everyone with genital lesions, and all partners of persons with genital lesions, should alert new sexual partners about HPV infection risk and take precautions to limit spread of HPV.

Pregnancy 389

Infections, including vulvovaginal candidiasis, bacterial vaginosis, genital herpes simplex, human papillomavirus, syphilis, cytomegalovirus, toxoplas-mosis, hepatitis B, and hepatitis C. These infections may be associated with pregnancy complications or perinatal infection.

Allethrin Scabies

Treatment of genital warts. Clin Dermatol 2004 22 48. 86. Buck H. Genital warts. Clin Evid 2004 12 1. 87. Beutner K et al. Patient-applied podofilox for treatment of genital warts. Lancet 1989 1 831. 88. Edwards L et al. Self-administered topical 5 imiquimod cream for external anogenital warts. Arch Dermatol 1998 134 25. 89. Moore R et al. Imiquimod for the treatment of genital warts a quantitative systematic review. BMC Infect Dis 2001 1 3. 90. Stone KM et al. Treatment of external genital warts a randomised clinical trial comparing podophyllin, cryotherapy, and electrodesiccation. Genitourin Med 1990 66 16. 91. Duus B et al. Refractory condylomata acuminata a controlled clinical trial of carbon dioxide laser versus conventional surgical treatment. Genitourin Med 1985 61 59. 92. Gross G et al. Systemically administered interferon alfa-2a prevents recurrence of condylomata acuminata following CO2-laser ablation influence of the cyclic low-close therapy regime. Genitourin...

Genital ulcer

Genital wart The name given to warts on the vulva, the vaginal wall, or the cervix in women and on the penis of men and on, around, and in the anus of all sexes. Genital warts result from a sexually transmitted disease caused by the human papillomavirus (HPV). In men and women, the warts may be single, occur in clumps, or become florid (a large mass). In HIV-positive people they may respond inadequately to treatment. Warts have been linked to more serious diseases, such as cervical cancer in women and anal neoplasia in men and women. In all cases of genital warts in women, a pap smear and follow-up treatment for HPV infection of the cervix must be conducted. It is now being suggested that men and women also receive anal smears regularly to detect any anal cancers that may develop from lesions caused by HPV. Both cervical and anal cancers are found at higher rates in HIV-positive people. They are also called condylomata acuminata.