HPV and Abnormal Pap Smear Results

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Family Papillomaviridae

Papillomaviruses resemble polyomaviruses in structure but are larger (Fig. 2.5). The virion is 55 nm in diameter, and the circular dsDNA genome is 8 kb in size. Replication and assembly of progeny virus occur in the nucleus. A partial listing of papillomaviruses is shown in Table 6.13. They are primarily mammalian viruses, but there are a few avian representatives in the family. The viruses are species specific. They infect epithelium and will undergo a complete replication cycle only in terminally differentiated cell layers. On infection, papillomaviruses induce cellular proliferation that leads to the production of warts or papillomas. In most infections these eventually resolve, but in some cases tumors can result. Papillomaviruses of humans, cattle, sheep, and cottontail rabbit have been shown to be associated with cancers in their natural hosts. Our knowledge of the replication of the papillomaviruses is limited because none will undergo a full replication cycle in any simple...

Screening and early detection The Pap smear

The Pap test is one of the better tests for detecting precursors of cancer. If followed by evaluation and treatment, it significantly reduces the mortality from cervical cancer. The purpose of the Pap test is to detect and treat cervical intraepithelial neoplasia (CIN) and, thus, prevent invasive cancer. Of those women treated for CIN, the likelihood of cure and survival is nearly 100 . Most women who develop cervical cancer have never had a Pap test, or have not had one in the past ten years. In the USA, more than half of those women who developed cervical cancer last year had never had a Pap test.4 Another 10 have not had a Pap test within five years, and 10 have had ineffective follow-up for an abnormal Pap test.5 Case-control studies in the UK have found that cervical cancer screening by Pap test has changed the incidence of cervical cancer over the past 20 years. The incidence of cervical cancer has fallen since 1960, mostly in the group of women aged 40-69, who are...

Evaluation of abnormal Pap test

Assuming an adequate specimen, normal or negative Pap test results can be followed as in Table 17.1. Controversies and variation in consensus of the evaluation of other readings occur. Atypical cells of undetermine sequence (ASCUS) may be the reading that causes much of the difficulty. One wants to neither overinvestigate with invasive procedures nor miss a cervical cancer before cure is possible. Use of HPV testing, often done routinely by the laboratory if ASCUS is detected, may determine a group of women with high-risk HPV infection who need closer and more frequent evaluation. Women with readings of ASCUS - favor low-grade squamous intraepithelial lesion (LGSIL) or high-grade squamous intraepithelial lesion (HGSIL) are found to be more likely to be infected with high-risk HPV.12 Follow-up evaluation for ASCUS can include repeat Pap testing in three months, HPV testing, and or colposcopy, especially if the woman is infected with high-risk HPV or has had previous abnormal Pap tests,...

Papillomaviruslinked cancers

Cervical carcinoma is the third most common cancer in women, with approximately half a million new cases and 280 000 deaths in the world each year. Most, if not all, of these cancers result from infection with a papillomavirus. The papillomaviruses are small DNA viruses of mammals and birds (Figure 22.2). There are well over 100 human papillomavirus (HPV) types, differentiated by their DNA sequences. They enter the body through small abrasions and infect keratin-making cells (ker-atinocytes) in skin or a mucous membrane. Each HPV type infects a preferred site, such as the hands or the genitals, and infection may result in a benign wart (papilloma) or a carcinoma. The papillomaviruses that infect the genitals are transmitted between individuals during sexual contact. Most papillomavirus infections do not become persistent, but in a minority of hosts the infection is not cleared by the host's immune response. In individuals who harbour a persistent infection there is a small risk of...

Micropapillomatosis Labialis

The lesions are not felt to be related to human papillomavirus (HPV) (21) and can be distinguished from condyloma acuminatum by the more uniform appearance of the projections. Histologically, the epithelium of MPL does not show the characteristic cytopathic effects of HPV (koilocytosis). The colposcopic appearance resembling endocervix may be alarming to neophytes (Table 9).


Papillomas (figures 2-2 and 2-3) are benign stalk-like (pedunculated) growths originating from the surface tissues. This outward growing, cauliflower-like, surface tumor is common within the oral cavity and may occur anywhere on oral mucosa. Surgical removal is curative. NOTE The lingual frenum of the tongue is a common site of papilloma development. This possibly is because of constant irritation of this tissue by irregular or sharp lower incisor teeth. Surgical removal is indicated. Notice the cauliflower shape of the papilloma. Figure 2-2. Papilloma, cauliflower shape. NOTE This papilloma does not have the normal warty (cauliflower-like) appearance. The biopsy confirmed an epithelial tissue abnormality. Variation in appearance from the classically-described lesion should always be considered in evaluation of tissue irregularity. Multiple papillomas may indicate secondary syphilis. Figure 2-3. Papilloma, variation in appearance. 2-4. PYOGENIC GRANULOMA

Pap smears

Although the major reason for periodic Papanicolaou (Pap) smear screening is the detection of cervical dysplasia and squamous cervical carcinoma, endometrial pathology may be detected by cytologic examination on routine Pap smears. Benign endometrial cells are detected in Pap smears more frequently in women on HRT than in women who are not on HRT, and abnormal endometrial histology is less frequent in follow-up of women on HRT than in women with endometrial cells who are not on HRT.30 Endometrial-type cells on cer-vicovaginal smears are associated with significant endometrial pathology in less than 9 of patients.31 Atypical glandular cells of undetermined significance (AGUS) are noted on less than 1 of Pap smears. Follow-up studies of patients with AGUS on Pap smears have demonstrated that between 25 and 60 of patients with follow-up biopsies have preneoplastic or neoplastic squamous or glandular lesions on biopsy, with squamous lesions being more common in premenopausal women and...

Human Papillomavirus

Hyperpigmented Labia

Human papillomavirus (HPV) belongs to the Papovaviridae family of double-stranded DNA viruses. Transmission of genital HPV occurs through skin-to-skin contact. There are more than 200 HPV types identified by PCR techniques. Different HPV types have preferences for different body tissues, with some types preferentially affecting the mucosa, others affecting thinner keratinized skin such as lower legs or dorsal hands, and still others found primarily on palms and soles. Common, plantar, and flat warts are examples of extragenital skin lesions. Genitomucosal lesions can be associated with significant clinical disease. HPV types 6 and 11 are most often associated with benign disease or low-grade cervical intraepithelial neoplasia. High-grade cervical intraepithelial neoplasia (CIN), cervical squamous cell carcinoma, vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, penile cancer, and anal cancers are traditionally associated with high-risk HPV types 16 and 18. Although...

Comparison of Icosahedral Viruses

A gallery of structures of viruses determined by cryoelec-tron microscopy is shown in Fig, 2,5, All of the images are to scale so that the relative sizes of the virions are apparent, The largest particle is the nucleocapsid of herpes simplex virus, which is 1250 A in diameter and has T 16 symmetry (the virion is enveloped but only the nucleocapsid is regular), The rotavirus and reovirus virions are smaller and have T 13, Human papillomavirus and mouse polyoma virus are pseudo-T 7, Ross River virus (family Togaviridae) is enveloped but has regular symmetry, with T 4, Several examples of viruses with T 3 or pseudo-T 3 are shown (dengue 2, flock house, rhino-, polio-, and cowpea mosaic viruses, of which dengue 2 is enveloped but regular and the rest are not enveloped), B19 parvovirus has T 1, The general correlation is that larger particles are constructed using higher triangulation numbers, which allows the use of larger numbers of protein subunits, Larger particles accommodate larger...

Infection As A Preventable Cause Of Cancer

Infectious agents more generally.13 Until recently, infectious agents that cause cancer were termed rare and inconsequential. This view, though widely held 10 years ago, is now known to be erroneous. Worldwide, infection remains among the most important causes of cancer. The International Agency of Research on Cancer (IARC) estimates conservatively that 15.6 of all malignancies, and 21 in developing countries, are attributable to infectious agents.14 In some countries, the proportion is substantially higher. For example, in The Gambia in the late 1990s, 62.5 of malignancies in men affected either the liver (of which 84 were considered attributable to hepatitis B or C) or stomach (at least 55 estimated to result from Helicobacter pylori infection). In Gambian women, 57 of cancers affect the liver, stomach, or uterine cervix (95 attributable to human papillomavirus, HPV).5,15 In terms of overall mortality age-adjusted numbers, cancers of the stomach for men and cervix uteri for women...

Adenovirus Pharyngitis

Lymphadenopathy maculopapular rash severe seborrheic dermatitis oral thrush white confluent patch with corrugated surface ( ORAL HAIRY LEUKOPLAKIA) along lateral borders of tongue penile warts ( CONDYLOMATA ACUMINATA) extensive multiple pruritic, pink, umbilicated papules 2-5 mm in diameter ( MOI.LUSCUM CONTAGIOSUM).

African Trypanosomiasis

PS cachectic generalized lymphadenopathy maculopapular rash severe seborrheic dermatitis aphthous ulcers white confluent patch with corrugated surface (orai. hairy leukoplakia) along lateral borders of tongue penile warts (condylomata acuminata) extensive multiple pruritic, pink, umbilicated papules 2 to 5 mm in diameter (molluscijm con tagiosum) .

Cervical Neoplasia in Pregnancy

A 25-year-old patient approximately 14 weeks pregnant by dates has a Pap smear reported as HGSIL (high-grade squamous intraepithelial lesion). On pelvic examination there is a gravid uterus consistent with 14 weeks size, and the cervix is grossly normal. Colposcopy and biopsy. A patient who is pregnant with an abnormal Pap smear should be evaluated in the same fashion as in a nonpregnant stale. An abnormal Pap smear is followed with colposcopy with the aid of acetic acid for better visualization of the cervix. Any abnormal lesions of the ectocervix are biopsied. CIN. Patients with intraepithelial neoplasia or dysplasia should be followed with Pap smears and colposcopy every 3 months during the pregnancy. At 6-8 weeks postpartum the patient should be reevaluated with repeat colposcopy and Pap smear. Any persistent lesions can be definitively treated postpartum.

Pharmacological Management Estrogens

Estrogens are used either systemically or topically. Side effects may include an increased risk for gynecological malignancies, fluid retention, depression, nausea, vomiting, elevated blood pressure, gallstones, and cardiovascular effects such as stroke and myocardial infarction. However, in addition to the aforementioned benefits of improved voiding function, hormone replacement therapy confers an overall benefit in mortality as compared to nontreated patients (24). Topical vaginal application through direct placement or vaginal implants are preferable because of the decreased systemic absorption and preferential local uptake (25). When mild atrophic changes of the vaginal epithelium are noted on pelvic examination despite systemic estrogen replacement, additional topical vaginal therapy may be useful in order to improve voiding function without incurring side effects from increasing the systemic administration. Yearly PAP smears and breast examinations should be performed when...

The answers are 303d 304g 305b 306h 307a

(Kutty, 3 e, pp 762-765.) Most patients with CML have the Philadelphia chromosome t(9,22) and the bcr abl fusion protein. Mucosa-associated lymphoid tissue (MALT) tumor has been shown to be secondary to H. pylori. Squamous cell carcinomas of the anus, penis, and cervix have been linked to human papillomavirus (HPV). Hepatitis B and C and hemochro-matosis are the major risk factors for hepatocellular carcinoma. Other risk factors include aflatoxin exposure and being from the Far East or Africa (high-incidence areas). Cigarette smoking is the most consistently observed risk factor for pancreatic cancer. Schistosomiasis is associated with squamous cell carcinoma of the bladder. Patients with BRCA1 gene on chromosome 17 present with breast cancer at a young age with a family history of breast or ovarian cancer. Vinyl chloride exposure is a risk factor for hemangiosarcoma of the liver. Patients with colonic polyps are at risk for developing colon cancer. Villous adenomas are more likely to...

Overwhelming Postsplenectomy Sepsis

Condylomata acuminata noted in perianal distribution remainder of physical exam normal. The term gay bowel syndrome is used in reference to enteric and perirectal infections that arc commonly encountered in immune-competent homosexual men in homosexuals with HIV, opportunistic organisms play a more important role. Common etiologic agents include Chlamydia trachomatis, lymphogranuloma venereum serovars, N. gonorrhoeae, HSV, Treponema pallidum, human papilloma virus, Campylobacter a pedes, Shigella, Entamoeba histolytica, and Giardia.

Family Polyomaviridae

Until recently, the polyomaviruses and the papillo-maviruses were considered to be two subfamilies within the family Papovaviridae. The name papova came from papilloma virus polyoma virus simian vacuolating virus ( SV40), three characteristic members of the enlarged family. Recently, the ICTV has elevated the two subfamilies to the status of full families, and that is the treatment followed here.

The Ventricular System

Communicating hydrocephalus is caused by oversecretion of CSF without obstruction in the ventricles or by CSF circulation or absorption problems from the subarachnoid space. Choroid plexus papilloma is a possible cause of oversecretion, a tumor in the subarachnoid space limits circulation, or meningitis may limit absorption into the superior sagittal sinus.

Traumatic Gas Gangrene

A 10-year-old child who lives in tropical Africa presents with multiple papillomatous skin lesions and pain in both legs. The first lesion had appeared on the leg as a small indurated papule that ulcerated into a granulomatous papilloma. Multiple papillomatous skin lesions seen, especially in intertriginous areas lesions were painless and exuding a serous fluid painful hyperkeratotic lesions seen on palms and soles both tibia were tender to palpation.

Established p53 inhibitors in the p53 dissociator assay

The p53 dissociator assay can also recapitulate more complex situations, such as the interplay of p53, E6-associated protein (E6-AP) and E6 of high-risk human papilloma viruses (HPV). Exposure to high-risk HPV is linked to cervical cancers, and the E6 protein of high-risk HPV has been shown to induce p53 degradation. To this purpose, E6 recruits the human host factor E6-AP, an E3 in the ubiquitin cascade that forms a direct thioester bond with ubiquitin. The trimeric complex of p53, high-risk HPV E6, and E6-AP results in the degradation of p53 via the ubiquitin cascade (Figure 2A) 20, 28, 70, 84, 96 .

P53 dissociator screens to identify proteins important for p53 biology

Recapitulating the biology of p53, E6-associated protein and high-risk human papilloma virus (HPV) E6 in the p53 dissociator assay. Infection with high-risk HPV is associated with more than 80 of human cervical cancers. (A) The E6 protein induces ubiquitin-mediated degradation of p53 through recruitment of the host factor E6-associated protein (E6-AP), an E3 in the ubiquitin cascade whose cysteine 833 forms a direct thioester with ubiquitin ( S- in the figure). (B) The complex interplay between two human and one viral protein(s) can be recreated in the p53 dissociator assay, since the combination of E6-AP and high-risk HPV E6 results in an Foa resistant (FoaR) phenotype on plates containing Foa (+Foa0.1 ). The interference with p53 is highly specific, since low-risk E6 from an HPV unable to cause cervical cancer does not confer Foa resistance. (C) The FoaR phenotype corresponds to reduced p53 protein levels that are seen not only in galactose

Prevalence in Penile Cancer Table 231

Prevalence of human papillomavirus (HPV) DNA in penile lesions in Europe and the United States Table 23.1. Prevalence of human papillomavirus (HPV) DNA in penile lesions in Europe and the United States The HPV status of verrucous carcinomas of the penis has been assessed in several reports of 26 cases, only three have been found to be positive for HPV-DNA (12 ), and all were positive for low-risk HPVs 13,15,25-28 . Some authors advocate that screening for HPV may be a useful adjunct in differentiating GCBL from verrucous carcinoma. Indeed, published reports suggest that GCBL is always associated with HPV infection. However, in view of our current understanding, the presence or absence of specific HPV types cannot be used to predict malignant transformation.

Interaction with PDZ Domain Containing Proteins

In the largest study to date, the frequency of p53 gene mutations was 33 (seven of 21) in SCC of the penis 48 . This included only 22 (two of nine) HPV-positive tumors, and 42 (five of 12) HPV-negative tumors. In a study of 45 French men with penile SCC, the p53 Arg Arg genotype was not a risk factor for the development of SCC, and no correlation was found between p53 polymorphism at codon 72 and the presence of HPV-DNA 49 . In contrast, two studies have compared the clinical outcomes of patients with HPV-positive versus HPV-negative penile carcinomas. Both reported no difference in lymph node metastasis rates or survival 52,53 . In a recent study, alterations pointing to a disturbed p16INK4A cyclin D1 Rb pathway are commonly present in penile carcinomas 54 . Three alternative mechanisms of disruption were identified (Fig. 23.1) activity of high-risk HPV and the resulting increase in p16INK4A expression was the most frequently detected mechanism, followed by p16INK4A hypermethylation...

The Role of Crosstalk Between Malignant Cells and Their Surroundings

Most research is being done in animal models or in cultured tumor cells. While we may now recognize the earliest pre-malignant changes that occur in isolated ductal cells, we do not yet have diagnostic tests than can detect those changes. Some research is directed toward developing more sensitive, non-invasive imaging. One possible screening procedure is somewhat analogous to the familiar Pap smear for cervical cancer (named for Dr. Papanicolaou, who developed the technique). The method is called breast ductal lavage, in which saline is introduced into individual ducts in the nipples and

Epidemiology and Etiology

In a review of risk factors for the development of penile cancers, strong risk factors identified with an odds ratio of more than 10 were phimosis, chronic inflammatory conditions such as bal-anoposthitis, lichen sclerosis et atrophicus, and treatment with psoralen and ultraviolet A 5 . A three- to fivefold increased risk was found for smoking, sexual history, and condyloma. Circumcision in the neonatal period was associated with a threefold decreased risk of penile cancer. Human papillomavirus (HPV) DNA has been identified in 40 to 50 of invasive penile carcinoma and 70 to 100 of carcinoma in situ 5 .

Embryonic Stem Cell Technology in Cancer Research

The first such TSG gene knockout was also the first TSG cloned, the RB1 gene (reviewed in ref. 55). In many ways the evaluation of this knockout mouse illustrates many of the challenges in the tumor suppressor gene field. Unlike RB1+ patients, Rb1+ mice do not develop retinoblastomas (56). The reason for this may be that, given the number of retinoblast cells at risk and their fleeting appearance in the early life of mice, there is simply not enough time, nor are there enough target cells at risk for acquiring somatic mutation of the wild-type allele. This could be called the target cell number and time dilemma. The natural history of the mouse (which is over two logs less massive than the average adult human and lives 2 years instead of 70) does not recapitulate that of the human. As it turns out, the fact that Rb1+- mice do not develop retinoblastoma was the impetus to pursue the idea that multiple genetic events, such as p53 pathway inactivation, may be required to induce...

Bloody Nipple Discharge

A bloody nipple discharge usually results from an intraductal papilloma. The treatment is total excision of the duct and papilloma through a circumareolar incision. Modern ductography does not reliably exclude intraductal pathology and is not a substitute for surgery in

Immortalization by DNATumor Virus Encoded Proteins

At least two decades ago, specific immortalizing genes were identified for adenovi-rus, polyoma virus, SV40 virus, and papillomavirus (6). Although each of them is capable of immortalizing many mammalian cells, SV40-virus-encoded large T-antigen (SV40 TAg) or its various mutant forms have been extensively used, either alone or by cotransfection with various other cooperative agents (7). In addition, the immortalization of cells by SV40 TAg has been achieved by various strategies, including direct transfection, retroviral-mediated transduction, or expression by site-specific recombination (7). Two other classes of oncogenes that are known to act cooperatively with SV40 TAg are human papillomavirus early proteins E6 and E7 and the adenovirus early proteins E1A and E1B. One common mechanism of cellular transformation and immortalization by all these proteins seems to be their ability to bind and inhibit the activities of many cell cycle proteins including the tumor suppressors, p53 and...

Premenopausal Adnexal Mass

A 28-year-old patient is seen in the emergency room complaining of lower abdominal discomfort for the last 5 days. She has no history of oral contraceptive medication, and her last pelvic examination was a year ago, which included a Pap smear, which was negative. On pelvic examination and on sonogram performed in the emergency room, a right 6-cm complex adnexal mass with no other abnormality is noted.

Molluscum Contagiosum

Moist Labia

Table 3 Human Papillomavirus Infections Table 3 Human Papillomavirus Infections Genital warts papillomatosis, Condylomata acuminata, varicella, herpes simplex, milia, nevi, basal cell carcinoma, folliculitis, keratoacan-thoma Conditions that can resemble mollusca contagiosa include genital warts, fol-liculitis, dermal nevi, milia, and sebaceous hyperplasia. The diagnosis is generally made clinically. However, when the presentation is atypical, the diagnosis can be made when the white central core is expressed and examined microscopically to visualize brick-shaped inclusion bodies. Treatment includes observation, destruction by cryotherapy or cantharidin, and expression of the white molluscum body. More recently, open trials have suggested that topical imiquimod cream applied overnight three nights a week is beneficial, and a controlled trial of 23 children showed that imiquimod used for 12 weeks cleared one-third of patients receiving active medication as compared to one of eleven...

Obstetrics and Gynecology

The answers are 468-e, 469-a, 470-d, 471-c, 472-b. (Fauci, 14 e, pp 562-568.) Most breast cancers present in the upper outer quadrant of the breast patients may present with a hard, circumscribed mass that is fixed to the skin or deep muscle. Cancer may be nodular with indistinct borders. Patients may also have nipple edema or retraction. A woman under the age of 30 years presenting with a mobile breast mass that has well-defined borders most likely has a fibroadenoma. However, breast cancer must still be ruled out since clinical exam and even mammography are not sufficient to exclude the diagnosis. Intraductal papilloma is a benign tumor patients often present with a bloody discharge from the nipple in the absence of a breast mass. Patients who present with an erythematous and

Overflow Incontinence After Lefort Surgery

The answer is a. (Rock, 8 e, pp 375-378.) Partial colpocleisis by the Le Fort procedure is reasonable for elderly patients who are not good candidates for vaginal hysterectomy and A& P (anterior and posterior) repair as treatment for vaginal and uterine prolapse. The technique involves partial denudation of opposing surfaces of the vaginal mucosa followed by surgical apposition, thereby resulting in partial obliteration of the vagina. Patients who are candidates for this procedure must have no evidence of cervical dysplasia or endometrial hyperplasia, have an atrophic endo-metrium, and no longer desire sexual function since the vagina is essentially obliterated and there is no longer access to the cervix or uterus via the vagina. Urinary incontinence can be a side effect of this procedure, so care must be exercised in the denudation of vaginal mucosa near the bladder. In a patient who already has urinary incontinence, the Le Fort operation would be relatively contraindicated....

Atrophic Vaginitis And Serosanguineous Discharge

The answers are 288-b,c,e, 289-a. (Hoskins, 2le, pp 78-79, 182, 197.) Human papillomavirus (HPV), in particular types 16, 18, and 31, has been linked to cervical neoplasia. HPV types 6 and 11 are associated with benign condyloma. Two types of vulvar dystrophies exist lichen sclerosus and hyperplastic dystrophy. When hyperplastic dystrophy is found to have atypical features, the lesion is thought to be premalignant. Lichen sclerosus is a benign condition that does not develop cellular atypia. 311. The answer is e. (Ransom 1997, p 53.) The lesions are condyloma acuminatum, also known as venereal warts. This is a squamous lesion caused by a human papillomavirus (HPV). The lesion reveals a treelike growth microscopically with a mantle that shows marked acanthosis and parakeratosis. Treatment options include local excision, cryosurgery, application of podophyllum or trichloroacetic acid, and laser therapy, although podophyllum is not recommended for extensive disease because of...

Postmenopausal Adnexal Mass

A 70-year-old patient comes into the gynecologist's office for annual examination. She complains of lower abdominal discomfort however, there is no weight loss or abdominal distention. On pelvic examination you find a nontender, 6-cm, solid, irregular, fixed adnexal mass. Her last examination was 1 year ago, which was normal, and it included an abnormal Pap smear.

Is Livergen Suitable For Three Months Pregnancies

The answer is a. (Braunwald, 15 e, pp 1118-1134.) Human papillomavirus (especially subtypes 16, 18, and 31) has an established relationship to abnormal Pap smears and cervical dysplasia. HIV, Chlamydia, or herpesvirus infections are not directly associated with cervical dysplasia. 484. The answer is a. (Braunwald, 15 e, p 48.) The current recommendation for workup of abnormal cervical cytology includes repeat Pap smear at 3 to 4 months, HPV DNA typing, or colposcopy, depending on the patient and her history. A Pap smear every 3 years is acceptable for low-risk patients with three negative annual consecutive Pap smears. There is no recommendation for early repeat Pap smear if a patient has a new sexual partner. Sexually active women should have annual cervical screening, with the exception of low-risk patients, who can discuss changing the screening interval with their physician.

Close Up Twitter Barely Legal

Lymphoepithelioma-like, 167 squamous cell, 161-164 urethral, 175 verrucous, 162-165 Caruncles hymenalis, 12 Cellulitis, 4, 86 Cervical carcinoma, 183 Cervical dysplasia, 74 Chancroid, 81-83 Chickenpox. See Varicella Chlamydia trachomatis, 80, 135 Circumcision, female genital, 6 Clitoris, 13 prepuce and frenulum of, 21 suspensory ligament of, 14 Clobetasol propionate, 51 Colle's fascia, 13 Condylomata acuminata, 4 Gardnerella vaginalis, 84 Genital anomalies imperforate hymen, 32, 33 longitudinal vaginal septum, 32 transverse vaginal septum, 32 vaginal agenesis, 31-32 vulvovaginal abnormalities, 34 Genital herpes virus infection, 3 Genital mucosa chronic ulcer of, 54 genetic, 55 Genital mutilation, 184 Genital staphylococcal infections, 85 Genital tuberculosis, 84 Genital warts, 4 therapy of, 75 Genitalia, ambiguous, 31 Granular cell tumors, 152-155 Granuloma inguinale, 79-80 Granuloma pyogenicum. See Pyogenic granulomas Hidradenitis suppurativa, 46, 48-49 Hidradenoma, papillary,...

Questions Answers On Bulky Epididymal

Human papilloma virus (HPV) serotypes 6 and 11 c. Human papilloma virus (HPV) serotypes 16 and 18 Malformations of the penis related to aberrant opening of the urethra include epispadias (opening on dorsal surface) and hypospadias (opening on ventral surface). Balanitis is inflammation of the glans penis, often related to poor hygiene and lack of circumcision. Peyronie disease is penile fibromatosis resulting in curvature of the penis. Condyloma acuminatum is a warty growth related to HPV infection, s Squamous-cell carcinoma of the penis is uncommon in the United States but can be related to HPV infection,

Pagets Disease of the Vulva Extramammary Pagets Disease

Paget Disease The Vulva

Figure 29 Vulvar intraepithelial neoplasia (VIN), usual type. (A) (See color insert) This VIN lesion is pigmented. (B) (See color insert) This is an example of a depigmented VIN lesion. (C) (See color insert) In the warty pattern, cytopathic features of human papilloma virus are prominent. (D) In the basaloid pattern, the entire epithelium is placed by small basaloid cells. Figure 29 Vulvar intraepithelial neoplasia (VIN), usual type. (A) (See color insert) This VIN lesion is pigmented. (B) (See color insert) This is an example of a depigmented VIN lesion. (C) (See color insert) In the warty pattern, cytopathic features of human papilloma virus are prominent. (D) In the basaloid pattern, the entire epithelium is placed by small basaloid cells.

Other Diagnostics

Colposcopic findings, i.e., a magnified view of vulvar dysplasia can be variable. Compared to cervical dysplasia, which most often has an acetowhite appearance with atypical vascular changes, vulvar dysplasia can occur with minimal colposcopic findings. A mild acetowhite appearance of the vestibule can occur and should not be confused with dysplasia. Examination of the non-hair-bearing areas is most amenable to colposcopy and most often mirrors similar processes on the cervix. Lesions on hair-bearing, keratinized portions can be subtler these lesions may extend into the pilosebaceous apparatus and may not be entirely visible. An important feature of vulvoscopy is how a lesion looks in comparison to its surroundings.

Anne Walling

Case I am turning into a big fat lump that just lies around eating, sleeping and feeling sorry for myself all the time This sudden outburst during a visit for a routine pap smear is completely out of character for Marie, a 44-year-old divorced schoolteacher who is usually smartly groomed, articulate, and vivacious. Tactful questioning reveals about a four-week history of excessive sleeping and feelings of fatigue, low stamina, and worthlessness. She has been snacking excessively and has gained about six pounds. Marie admits to severe blues during her freshman college year and after the births of her children, but she toughed it out. This time, she does not have the energy or will to continue her daily activities and she has called in sick for the first time ever as she just could not face doing a mediocre job for the class.

Intrauterine devices

Considerable debate remains regarding IUD removal because of the risk of the development of endometritis or salpingitis. Contraindications for IUD placement include pregnancy, genitourinary malignancy, cervicitis, recent abnormal Pap smear, dysfunctional uterine bleeding of unknown etiology, salpingitis, and history of previous ectopic pregnancy.


A 38-year-old white female visits her gynecologist for a routine Pap smear. Pallor cervical tenderness a few small, raised, flat lesions on cervix genital warts also seen on vulva ( CONDYLOMATA ACUMINATA). Rounded basophilic cells on Pap smear with large nuclei occupying most of surface nuclei show mitoses and coarse clumping of chromatin with perinuclear halo ( SEVERE KOILOCYTJC DYSPLASIA).

Spermicidal devices

Of a properly applied, non-defective condom with a properly applied spermicidal device has a failure rate of virtually zero. Though not optimally effective as a prevention strategy for sexually transmitted disease (STDs), evidence suggests that spermicidal preparations afford women significant protection against most common STDs, including gonorrhea, trichomonas, syphilis, and human papilloma virus (HPV).

Whooping Cough

A 10-year-old child who lives in tropical Africa presents with multiple papillomatous skin lesions and pain in both legs. The first lesion had appeared on the leg as a small indurated papule that ulcerated into a granulomatous papilloma. Multiple papillomatous skin lesions seen, especially in intertrigi-nous areas lesions were painless and exuding a serous fluid painful hyperkeratotic lesions seen on palms and soles both tibia were tender to palpation.


FIGURE 6.27 Genome organization and transcription map of papillomaviruses. (A) Genome organization of bovine papillomavirus 1. (B) Genome organization of human papillomavirus 11. (C) Transcription map of human papillomavirus 11. Genomes have been linearized at the upstream regulatory region (LCR or URR) for ease of presentation. All ORFs are transcribed from left to right from one DNA strand. Promoters are shown as turquoise arrows sites of poly(A) addition with orange arrows labeled late (AL) or early (AE initiation codons are shown as open red triangles. The symbol A joins two ORFs that are translated together as a fusion protein from a spliced mRNA for example, E1iAE4 is a fusion protein translated from an mRNA in which the first 5 codons of protein E1 (ORF1) are spliced to the 85 C terminal codons of E4 (ORF2). Adapted from Nathanson et al. (1996, p. 27) and from Fields et al. (1996, pp. 2051, 2052). Human Papillomaviruses More than 25 HPVs cause genital warts, which are among the...

Review Questions

A 28-year-old woman comes to the physician because of a big lump on her neck that she found 3 days ago. She says that she is rarely sick and only goes to the doctor every few years for a Pap smear. Her temperature is 38.1 C (100.5 F). Physical examination shows a 2.3-cm nontender cervical lymph node. Excisional biopsy of the lymph node is most likely to show which of the following

Condyloma Acuminatum

This disease is caused by the human papilloma virus (HPV). It is the most common overall STD in women, as well as the most common viral STD. Transmission can occur with subclinical lesions. HPV subtypes 16 and 18 are associated with cervical and vulvar carcinoma. Predisposing factors include immunosuppression, diabetes, and pregnancy.


The incidence of cervical cancer has decreased since the 1950s and stabilized in the 1980s in the USA. Approximately 13 000 women will develop cervical cancer yearly, and approximately 4500 will die from it.1 Because the incidence and mortality of cervical cancer have decreased by more than 40 since 1973 and the push for mass screenings, the Agency for Health Care Policy and Research (AHCPR) has given Pap tests an A recommendation, despite poor evidence for their efficacy.2 In many cases, cervical cancer can be prevented.

When and how often

The frequency, initiation, and cessation of regular Pap tests are controversial. The 2003 American Cancer Society (ACS) guidelines are shown in Table 17.1.10 Further modifications of these guidelines may include a test for human papilloma virus (HPV), which may delineate those women who need closer follow-up and evaluation. A study of more than 2000 women found that those with normal Pap tests but with positive detection of abnormal HPV were more likely to have subsequent abnormal Pap tests (odds ration 2.7) 11 fifteen per cent developed abnormal pap tests within five years. Table 17.1 2003 American Cancer Society guidelines for frequency of Pap tests Women begin regular Pap tests after three years of initiation of vaginal intercourse or at age 21 years Pap tests performed annually if slide tests are used or every other year if liquid-based tests are used After age 30 years, women with three normal Pap tests in a row may be screened less frequently (approximately every three years),...


Colposcopy makes it possible to detect cancer of the cervix in its early stages, examine tissue from which an abnormal Pap smear has been obtained, and monitor areas of the cervix from which malignant lesions have been removed. Colposcopy is also used to monitor women who are at risk for developing cervical cancer because their mothers were given diethyl-stilbestrol (DES) during their pregnancy. Colposcopy may also be used to examine male genitalia when sexually transmitted diseases are suspected. Variations from Normal. Benign, precancerous, or cancerous lesions may be detected during a colposcopy. Male sexually transmitted diseases that can be identified with this procedure include condylomata or human papillomavirus.


In men, a diagnosis of NGU is based on the microscopic finding of four or more PMNs per microscope field at X1000 magnification without the presence of intracellular gramnegative diplococci. However, the finding of microscopic evidence of gonococcal infection does not preclude concurrent infection with C. trachomatis since mixed infections are commonly encountered. While five to more than ten PMNs per high-power field on smears made from endocervical swabs have been found to be associated with C. trachomatis infection in women by some workers, demonstration of inclusions in cells obtained from infected sites is relatively insensitive because inclusions are rarely detected in female genital tract exudates. Although intracytoplasmic inclusions have been detected in Pap smears obtained for cervical cytologic investigations, interpretation of these smears for C. trachomatis infection is difficult, and the sensitivity and specificity of the technique are unacceptably low.43


A 35-year-old patient comes to the gynecologist's office complaining of infertility for 1 year. The patient and her husband have been trying to achieve pregnancy for > 1 year and have been unsuccessful. There is no previous history of pelvic inflammatory disease and she used oral contraception medication for 6 years. The pelvic examination is normal, and a Pap smear is done.

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A 20-year-old sexually active female presents for an annual exam. She tells you she has had four sexual partners in the past, she has participated in unprotected intercourse sometimes, and her age at first coitus was 15. She has a 5-pack-year tobacco history. Her family history is positive for early coronary artery disease in her father and paternal grandfather. On physical exam, she is overweight. Otherwise her exam is normal. On pelvic exam, there are no cervical lesions, and a Pap smear is obtained. 483. Several days later, the Pap smear result is reported as a low-grade squamous intraepithelial lesion (LGSIL). Which infectious agent is most likely associated with this result a. Human papillomavirus (HPV) b. Have an annual Pap smear c. Have a repeat Pap smear if and when she changes sexual partners d. Have Pap smear repeated every 3 years

Vulvar Neoplasia

The relation of human papilloma virus (HPV) infection to the development of cervical carcinoma suggests that a similar process may contribute to vulvar neoplasia (25) but additional epigenetic events (26) may be active in the progression to vulvar neoplasia. HPV-mediated transformation of human epithelial cells has been recognized as a multistep process resulting from the deregulated transcription of the viral oncogenes, E6 and E7, in proliferating cells. Interference with cell cycle regulators induces genetic instability and oncogenic alterations may lead to a malignant pheno-type with tumor cell immortalization and inactivation of tumor suppressor genes. But, it has been suggested that there are two pathways leading to the development of SCC of the vulva (27). As with cervical carcinoma, one route is HPV dependent with premalignant changes of vulvar intraepithelial neoplasia analogous to cervical disease. But, an HPV-independent genesis without high-risk HPV seems to occur, although...

Anatomy Vulva

The vestibule is the medial (central), mucosa-covered part of the vulva. On embryologic, anatomic, and architectonic grounds, the correct term is vestibule of the vagina'' not vulvar vestibule,'' as sometimes appears in the literature (2). The vestibule is composed of loose fibroelastic and smooth muscular tissue without fat. The boundaries of the vestibule are Hart's lines laterally, the hymenal ring medially, the frenulum of the clitoris anteriorly, the fourchette posteriorly, and Colles' fascia deeply. The vestibule contains the urethral meatus and vaginal opening in the midline. The ostia of the greater vestibular (Bartholin's) ducts may be seen with the naked eye in the five and seven o'clock positions just external to the hymen. Minute, soft, nonbranching, pink polyps, the vestibular papillae, are a normal finding in one-third of women in the reproductive age group, although uncommon after menopause (Fig. 1) (3). They may be acetowhite and must be...


Genital Warts Condylomata acuminata or genital warts are caused by the human papilloma virus (HPV). Patients may complain of vulvar irritation or itching and typically note the appearance of multiple small warty lesions of the vestibule, inner labia minora, and perianal region.


The urinary blood fluke, Schistosoma hematobium, is a parasite which occurs in Egypt, Africa, and in parts of the Middle East. The general process of development in the first stages is the same for all blood flukes. The adult urinary blood fluke enters the body of the final host, a human, and matures in the venous plexuses of the bladder, prostate, and uterus. Eggs are passed in the urine or retained in the tissues, particularly the bladder wall and the female genital organs. Among the problems caused by this parasite are fibrosis, ulceration, and granuloma and papilloma formation, bladder wall calcification, chronic cystitis, pyelitis, and pyelonephritis. In Egypt, bladder cancer is common in advanced cases.


The answer is b. (Fitzpatrick, 3 e, pp 149, 170, 766-767, 772-775, 797.) The description of the skin lesions is most consistent with mollus-cum contagiosum. This is a self-limited viral infection due to a pox virus (molluscum contagiosum virus) seen in children, sexually active adults, and HIV-infected patients. These lesions characteristically have a central keratotic plug that gives them the appearance of being dimpled (umbilica-tion). The lesions resolve spontaneously. Common warts or verrucae vulgaris are due to human papillomavirus (HPV). Warts are firm, hyper-keratotic, round papules that are 1-10 mm in diameter. They have no umbilication but have a predilection for sites of trauma including hands, 72-73. The answers are 72-b, 73-a. (Fitzpatrick, 3 e, pp 540-553.) Sezary syndrome is a cutaneous T-cell lymphoma (also called mycosis fungoides) characterized by an erythroderma (a generalized erythema, scaling, and thickening of the skin) and leukocytosis. Abnormal circulating T...

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A 53-year-old woman presents to your office with questions about hormonal replacement therapy (HRT). She has been experiencing hot flashes and night sweats. She has not menstruated for one year. She has no risk factors for cardiovascular disease. She is 5'6 and weighs 120 lbs. Her gynecological examination is normal as well as her Pap smear. Her breast examination and mam-mography are also normal. She wonders about the risks and benefits of HRT given her health status.

Clinical Picture

They can occur on any part of the skin but predominate in exposed areas, mainly the face, forearm and back of the hand. They are single or multiple, isolated or confluent, hemispheric, well-limited and 3-5 mm up to 1 cm, rough, dry, skin-colored or gray and asymptomatic. They involute within an average of two years (Fig. 55.1). Generally they are sessile, but on the eyelid they are filiform and can be associated with conjuntivitis and keratitis. When they occur on the edge of a fingernail, they cause ungual dystrophy and are painful. If they affect genitals, they are more keratosic and less vegetative than condylomas. When they are localized on the inner surface of the lips or the oral mucosae, they are called papillomas (HPV-6 and -11), are vegetative and single or multiple. They can grow rapidly and constitute a picture known as florid oral papillomatosis. They can be few or abundant, and sometimes, because of the Koebner phenomenon, they have a linear configuration (Fig. 55.2)....