Is colposcopy warranted in women with external anogenital warts?

OBJECTIVES.: To determine the prevalence of cervical dysplasia, diagnosed cytologically (squamous intraepithelial lesion [SIL]) or histologically (cervical intraepithelial neoplasia [CIN]), in women with external anogenital warts, and to determine the discriminating risk factors between those with and without cervical dysplasia. MATERIALS AND METHODS.: Chart review of women referred to colposcopy for external anogenital warts from 1990 to 1999. Human papillomavirus risk factors predictive for cervical dysplasia were assessed by logistic and Cox regression models. RESULTS.: There were 496 patients in this study. The prevalence of SIL by cytology was 20%: 18% low-grade squamous intraepithelial lesion and 2% high-grade squamous intraepithelial lesion. The combination of Pap smear and colposcopically directed biopsy identified dysplasia (SIL or CIN) in 30%, 4% of which were high-risk lesions (high-grade squamous intraepithelial lesion or CIN 2,3). Colposcopy performed much better than the Pap test alone in detecting CIN 2,3 lesions; 16 of 18 cases of CIN 2,3 diagnosed on biopsy had Pap smear results of low-grade squamous intraepithelial lesion or less, 7 of which were normal. Two thirds of those diagnosed with CIN 2,3 were aged 25 years and older. No differences in human papillomavirus infection risk factors were found between women with and without cervical dysplasia. CONCLUSIONS.: The high prevalence of CIN 2,3 in women with external anogenital warts warrants evaluation with colposcopy, particularly in women aged 25 years and older.     

Cytopathology update on atypical squamous cells

The most common abnormality reported by cervical cytology (Pap tests) is atypical squamous cells (ASC). The two subcategories are ASC of undetermined significance (ASCUS) and ASC, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). ASCUS show morphology suspicious for a low-grade lesion, while ASC-H cells are suspicious for a high-grade process. ASCUS account for most ASC reports, and the 2002 median ASCUS reporting rates were 3.1% for conventional smears and 4.1% for liquid-based preparations. Reporting rates for squamous intraepithelial lesions and cancer (SIL+) were also higher for liquid-based preparations, and thus the median ASC/SIL+ ratio was lower for liquid-based preparations (1.27) than for conventional smears (1.44). Interobserver reproducibility for ASC is generally considered lower than for other squamous epithelial abnormalities. Women with ASCUS may be managed by human papillomavirus DNA testing, repeated cytology, or colposcopy, while women with ASC-H should generally proceed to colposcopy.     

Postpartum evolution of cervical squamous intraepithelial lesions with respect to the route of delivery

OBJECTIVE.: To analyze the effect of the mode of delivery on the evolution of cervical squamous intraepithelial lesions. MATERIALS AND METHODS.: A chart review was performed of all pregnant women referred to the Northwestern Memorial Hospital Colposcopy Clinic between January 1990 and December 1998. Postpartum changes in the Pap smear and in a combined cytologic, histologic, and colposcopic impression of cervical status were evaluated. Data were analyzed using the chi, Fisher exact test, or Student t test. RESULTS.: Antepartum cytology was atypical squamous cells of undetermined significance in 23 women (7.1%), low-grade squamous intraepithelial lesions in 226 women (69.3%), and high-grade squamous intraepithelial lesions in 77 women (23.6%). Vaginal delivery occurred in 300 women (92.0%); 6 women (1.8%) had an elective cesarean section, and 20 women (6.1%) underwent a cesarean section after laboring. Of 306 women who had postpartum Pap smears, 37.9% had no change, 58.8% had improvement, and 3.3% had worsening of their cervical cytology. The rates of improvement of postpartum Pap smears were 164/285 (57.5%) following a vaginal delivery and 16/21 (76.2%) after a cesarean section (p = .81). Similarly, using a combined histologic, colposcopic, and cytologic evaluation of the cervix, the route of delivery did not affect postpartum cervical status (p = .68). CONCLUSION.: The route of delivery did not appear to influence the evolution of cervical squamous intraepithelial lesions during pregnancy and the puerperium.     

Papillomavirus found in anorectal squamous carcinoma, not in colon adenocarcinoma.

We used polymerase chain reaction DNA amplification methods for the detection and typing of genital human papillomaviruses in paraffin-embedded tissue sections of five patients with anorectal squamous cell carcinoma and 22 patients with colonic adenocarcinoma. The cases were further tested by in situ hybridization with biotin-labeled probes specific for human papillomavirus types 6/11, 16/18, and 31/33/35. By polymerase chain reaction, human papillomavirus DNA was demonstrated in all of the cases of anorectal squamous cell carcinoma and in none of the cases of colonic adenocarcinoma for which analyzable DNA was available. Tumor cell nuclei stained for human papillomavirus DNA by in situ hybridization in four of the five cases of squamous cell carcinoma and in none of the cases of colonic adenocarcinoma. We conclude that human papillomavirus types usually associated with malignant transformation are uniformly present in anorectal squamous cell carcinoma but are absent from adenocarcinoma of the colon.     

Role of human papillomavirus in squamous cell metaplasia-dysplasia-carcinoma of the rectum

Primary colorectal squamous cell carcinoma (SCC) and squamous dysplasia are uncommon and little is known about their pathogenesis. Most have been reported in association with ulcerative colitis and other chronic disease states. Although cervical and anal SCC have been strongly linked to human papillomavirus (HPV) infection, the role of HPV in rectal squamous carcinoma has not been well-examined. We evaluated 3 cases of primary rectal SCC for the presence of high-risk HPV by immunohistochemistry for p16(INK4A), in situ hybridization, and polymerase chain reaction. HPV type 16 was detected by polymerase chain reaction in all cases. In addition, all cases exhibited diffuse strong reactivity for p16(INK4A) and punctate nuclear staining by Ventana HPVIII in situ hybridization. The presence of HPV 16 in all three cases suggests that high-risk HPV infection is a risk factor for rectal SCC, particularly in patients with underlying chronic inflammatory disease processes or altered immune status. Further studies are warranted to determine if SCC occurring more proximal in the colon are also HPV-dependent or occur via another, HPV-independent pathway.     

Ancillary Diagnostics in Gynecologic Cytology

Cytology has been the mainstay of cervical dysplasia and cancer screening in the United States. The specificity of a woman harboring a high-grade lesion when identified as high-grade squamous intraepithelial lesion on Pap test is high; however, the test suffers from low sensitivity. Epidemiology studies have demonstrated that human papillomavirus (HPV) types 16 and 18 account for most cervical squamous cell carcinomas. Tests have been developed to identify high-risk HPV, some specifically to identify HPV 16 and 18. Simultaneous to the increase in HPV detection methods, interdisciplinary groups are making recommendations on the managerial use of the tests.     

Diagnostic Accuracy of Cervical Low-Grade Squamous Intraepithelial Lesions Is Improved With MIB-1 Immunostaining.

There is considerable interobserver variation in the diagnosis of low-grade squamous intraepithelial lesion that involves mature squamous epithelium. Our aim was to evaluate the utility of MIB-1 immunostaining as an adjunct test to increase diagnostic accuracy. Consecutive cervical biopsies originally diagnosed as normal (n = 26) or low-grade squamous intraepithelial lesion (n = 23) were reviewed by three pathologists to obtain a consensus diagnosis. MIB-1 immunostaining was performed, and positive staining was defined as a cluster of at least two stained nuclei in the upper two thirds of the epithelial thickness. Human papillomavirus (HPV) DNA detection was performed using a polymerase chain reaction assay. All cases were subsequently reclassified as low-grade squamous intraepithelial lesion (LSIL) or normal (NL) when two or three of three gold standard criteria were satisfied (LSIL gold standard criteria = consensus diagnosis of LSIL, HPV+, MIB-1+; NL gold standard criteria = consensus diagnosis of NL, HPV-, MIB-1-). Using the gold standard diagnoses, we have identified that 14 normal cases (36%) were originally overdiagnosed as LSIL, and one LSIL case (10%) was originally underdiagnosed as normal. All MIB-1-positive cases were HPV+ and identified as LSIL in the consensus review. All MIB-1-negative cases were NL by gold standard criteria. The sensitivity (1.0) and the specificity (1.0) of MIB-1 staining for identifying LSIL were superior to the sensitivity (0.9) and the specificity (0.8) of HPV testing. In conclusion, MIB-1 is a highly sensitive and specific marker for identifying low-grade squamous intraepithelial lesion and is helpful in verifying the diagnosis of equivocal cases.     

Pseudoangiosarcomatous squamous cell carcinoma: first case report on penis

Pseudoangiosarcomatous squamous cell carcinoma, also called pseudovascular, pseudoangiomatoid or adenoid pseudovascular carcinoma, is an uncommon and highly aggressive variant of squamous cell carcinoma. Histologically, it is characterized by proliferation of atypical keratinocytes with acantholysis and formation of pseudovascular spaces, forming anastomosed channels lined with neoplastic cells that invade the dermis. These cells are positive for cytokeratin and negative for vascular markers such as CD31 and CD34. There are few reports of this variant in the literature. Skin, breast, lung and vulva involvement have been described, but to the best of our knowledge, no cases involving the penis has been described. This study aims to describe the first case of angiosarcomatous squamous cell carcinoma of the penis. The patient presented with a painful lesion in the penis associated with urinary retention. Macroscopic findings exhibited an ulcerative vegetating lesion that involving the entire glans and part of the penile body, as well as infiltration of penile structures and scrotal skin. Microscopy shows atypical proliferation of sarcomatous keratinocyte pattern mimicking vascular spaces. Human papilloma virus (HPV) biomarkers and polymerase chain reaction (PCR) were all negative. Advanced penile squamous cell carcinoma with aggressive lymph node metastasis. This report presents the first case of penile pseudoangiosarcomatous squamous cell carcinoma, as an important differential diagnosis.     

Human papillomavirus‐related basaloid squamous cell carcinoma of the bladder associated with genital tract human papillomavirus infection

Basaloid squamous cell carcinoma is a biologically aggressive neoplasm mainly found in the head and neck region. Recently, four cases of basaloid squamous cell carcinoma of the bladder have been reported, and three of them occurred in patients with neurogenic bladder, repeated catheterizations and human papillomavirus infection of the urinary tract. To the best of our knowledge, none of the patients affected by basaloid squamous cell carcinoma of the bladder described in the literature had documented genital involvement by human papillomavirus. Herein, we describe the case of a woman with neurogenic bladder affected by basaloid squamous cell carcinoma of the bladder and by a concomitant genital tract human papillomavirus infection.     

Vulvar cancer in human immunodeficiency virus-seropositive premenopausal women: a case series and review of the literature

This review describes three cases of human immunodeficiency virus-infected women who were diagnosed with vulvar cancer before age 40 years. A retrospective chart review was performed for three patients who were younger than 40 years of age and who had histologically confirmed invasive squamous cell carcinoma of the vulva diagnosed between 1999 and 2002. Demographic, clinical, and laboratory data were recorded. Three human immunodeficiency virus-seropositive women were diagnosed with invasive squamous cell carcinoma of the vulva, stages IA, IB1, and III. All cases were characterized by extensive surrounding vulvar, vaginal, and cervical intraepithelial neoplasia. CD4 cell counts were 250, 330, and 900 cells/uL. Two patients experienced previous acquired immune deficiency syndrome-defining illnesses: toxoplasmosis and cervical cancer. Vulvar cancer in young human immunodeficiency virus-seropositive women may be associated with other human papillomavirus-related diseases and immunosuppression, as evidenced by low CD4 counts and the presence of antecedent acquired immune deficiency syndrome-defining illnesses.     

Noninvasive squamous lesions in the urinary bladder: a clinicopathologic analysis of 29 cases

Noninvasive squamous lesions are distinctively uncommon in biopsies of the urinary bladder with the exception of nonkeratinizing squamous metaplasia. The clinical significance of these squamous lesions in the bladder remains to be explored. A total of 29 cases of transurethral biopsies and resections of the bladder containing noninvasive squamous lesions (excluding nonkeratinizing metaplasia) were studied from the consult files of one of the authors. These cases included keratinizing squamous metaplasia (5), verrucous squamous hyperplasia (5), squamous papilloma (5), condyloma acuminatum (3), and squamous cell carcinoma in situ (CIS) (11). Immunohistochemistry for epithelial growth factor receptor (EGFR) and in situ hybridization for wide-range human papillomavirus was performed on 23 cases. The follow-up period ranged from 2 months to 3 years with an average of 1.5 years. After the initial diagnoses in biopsies of the bladder, 10 patients received cystectomies, and 7 patients received repeat tissue sampling of the bladder. Of the 5 patients with keratinizing squamous metaplasia, 2 patients had invasive urothelial carcinoma with squamous features in their cystectomy specimens at intervals of 3 and 14 months, respectively, 1 had persistent keratinizing squamous metaplasia on rebiopsy. Of the 5 patients with verrucous squamous hyperplasia, 1 patient had invasive squamous cell carcinoma at cystectomy at an interval of 14 months, 1 had squamous cell CIS on rebiopsy, 1 had persistent verrucous squamous hyperplasia on rebiopsy, and 2 had no evidence of disease at 6 and 24 months. Of the 5 patients with squamous papilloma, 1 patient had low-grade urothelial carcinoma at cystectomy at an interval of 21 months (h/o low-grade urothelial carcinoma preceding papilloma diagnosis), 2 were free of lesions at rebiopsy. Of the 3 patients with condyloma acuminatum, 1 had squamous CIS at cystectomy at an interval of 3 months, 1 had invasive squamous cell carcinoma at 20 months. Of the 11 patients with squamous cell carcinoma in situ (CIS), 3 patients had invasive squamous cell carcinoma at intervals of 2, 3, and 4 months, respectively, 1 had invasive urothelial carcinoma with squamous features in cystectomies at an interval of 12 months, 1 had squamous cell CIS at 10 months, 1 had high-grade urothelial carcinoma (not otherwise specified) at rebiopsy at an interval of 6 months, and 1 had no evidence of disease at 8 months. Among the 9 patients with invasive carcinoma, 4 patients died in the period of 0.5 to 3 years after the diagnoses. Immunohistochemical study with EGFR demonstrated strong signals in 20 cases and no signals in 2 cases. Wide-range human papillomavirus DNA signal was detected in 1 case of condyloma acuminatum and 1 case of squamous cell CIS. Keratinizing squamous metaplasia, verrucous squamous hyperplasia, and condyloma acuminatum in the urinary bladder can be associated with subsequent or concurrent in situ, or invasive squamous carcinoma and should be closely followed. Squamous cell CIS in the urinary bladder is often associated with subsequent or concurrent invasive carcinoma with squamous differentiation. Enhanced expression of EGFR in these bladder squamous lesions suggests that EGFR may represent a logic therapeutic target in those squamous lesions that are difficult to manage clinically.     

Keratinising squamous metaplasia of the bladder: natural history and rationalization of management based on review of 54 years experience

OBJECTIVE: To review our experience of keratinising squamous metaplasia of the bladder as a predictor for the development of cancer and other complications, and formulate a policy for its management. MATERIALS AND METHODS: A retrospective review (1945-1999) identified 34 patients with histologically proven keratinising squamous metaplasia (27 males and 7 females, average age 50 years, range 13-80 years). The histological criteria used to diagnose keratinising squamous metaplasia were squamous metaplasia of the urothelium with keratinisation and/or hyperkeratosis and/or acanthosis. Female patients with non-keratinising squamous metaplasia (vaginal metaplasia) were excluded. RESULTS: Four patients had synchronous bladder carcinoma (three advanced with early death; one localised, cured by cystectomy). Another 14 patients had extensive metaplasia (Group A, >50% of mucosal involvement). Three cases had cystectomy and cure. Six cases (out of 11) developed subsequent cancer (4 advanced and early death, two localised and cured by cystectomy). One other case died of obstructive uropathy secondary to squamous metaplasia. Two cases died of unrelated causes.Sixteen patients had limited squamous metaplasia (Group B, <50% involvement mucosal surface). Twelve patients had endoscopic resection, extraction bladder calculus etc. with no further complications. Another two patients underwent urinary diversion. Two patients (out of 16) developed subsequent cancer both with advanced disease and early death. CONCLUSION: Keratinising squamous metaplasia of the bladder is a significant risk factor for vesical carcinoma and complications, such as bladder contracture and ureteral obstruction. This risk of complications increases with more extensive bladder mucosal involvement. The wide variation in lag time to the development of complications necessitates indefinite follow-up. Selected patients with extensive bladder involvement and long life expectancy should be offered cystectomy.     

A "see and treat" management for high-grade squamous intraepithelial lesion pap smears

OBJECTIVE.: This study evaluates a "see and treat" intervention for high-grade squamous intraepithelial lesions (HSIL) on Pap smears. This is a case control study comparing cost-effectiveness, patient compliance, and pathology obtained from immediate colposcopy and large loop excision of the transformation zone of the uterine cervix. (LLETZ) MATERIALS AND METHODS.: At our institution before the onset of the study, a chart review of 100 patients with HSIL Pap smears was performed. This was the control group. Ninety percent of the patients' in the control group who had HSIL on Pap eventually had LLETZ. The next consecutive 100 women presenting to the clinic who met the same inclusion criteria underwent colposcopy and LLETZ at the same visit and were compared with the control group. Demographics, pathology, compliance, and cost were analyzed. RESULTS.: One hundred patients were treated with one visit colposcopy/LLETZ intervention. Histologic diagnosis of cervical intraepithelial neoplasia (CIN) 2,3 was confirmed in 94% of patients. Two percent of the patients had CIN 1, 1% had no histologic evidence of CIN, and 3% had microinvasive cancer to a depth of 0.5-1.5mm. Cost analysis revealed savings of $35,000 for the institution. Patient compliance was improved with a kept appointment rate of 82%. CONCLUSIONS.: "See and treat" intervention for HSIL Paps was an effective tool. Treating HSIL Paps without a separate visit for colposcopy is a cost-effective management. This method was more convenient for patients with only one disruption of daily schedules.     

The distribution of low and high-risk HPV types in vulvar and vaginal intraepithelial neoplasia (VIN and VaIN)

It has been proposed that low-grade vulvar and vaginal lesions (VIN 1 and VaIN 1) are flat condylomas and should be designated as such. Moreover, their relationship to high-grade lesions (VIN 3 and VaIN 3) is unclear. Accordingly, this study was undertaken to address these issues by comparing the distribution of human papillomavirus (HPV) types in vulvar and vaginal intraepithelial lesions. We identified 33 cases of VIN 1, 34 cases of VIN 3, 17 cases of VaIN 1, and 16 cases of VaIN 3. In addition, 36 cases of low-grade squamous intraepithelial lesion (LSIL) in the cervix and 116 cases of cervical high-grade squamous intraepithelial lesion were used for comparison. Polymerase chain reaction analysis was performed using both the Roche PGMY and DDL SPF 10 systems. In cases where HPV was detected, the majority of low-grade and high-grade lesions contained a single HPV type. However, a minority of cases were found to have multiple HPV types. Of the VIN 1 cases, a low-risk virus was seen in 22 (67%), with HPV 6 or 11 accounting for 14 (42%). A high-risk virus was detected in 14 (42%) of cases of which 2 (6%) contained HPV 16. Of the VIN 3 cases, all had high-risk HPV of which 31 (91%) were found to have HPV 16. Of the VaIN 1 cases, 6 (35%) were found to have low-risk HPV types. HPV 6 or 11 were not found in these cases. High-risk virus was seen in 13 (76%) VaIN 1 cases, with 1 (6%) containing HPV 16. HPV was detected in 15 of 16 (94%) VaIN 3 lesions, all of which had high-risk types. HPV 16 was found in 8 (50%). In contrast, 2 (6%) of cervical LSIL had low-risk HPV (HPV 6 and 11), whereas 34 (94%) of LSIL cases had high-risk HPVs. Of the cervical high-grade squamous intraepithelial lesion cases, 100% had high-risk HPVs of which 87 (75%) were found to have HPV 16. The findings demonstrate that a significant number of low-grade vulvar and vaginal lesions contain high-risk HPV types, supporting their designation as low-grade intraepithelial lesions rather than flat condylomas. The low frequency of HPV 16 in VIN 1 compared with VIN 3 suggests they are distinct lesions or that HPV 16 is critical in the progression to VIN 3. Finally, comparison of the distribution of HPV in the vagina and vulva suggests that VaIN is more closely related to cervical intraepithelial neoplasia than to VIN.     

Cost-effectiveness of adding human papilloma virus testing to a managed care cervical cancer screening program

OBJECTIVE: The purpose of this study was to demonstrate a methodology for auditing the impact of HCII testing on the direct cost of cervical cancer cytological screening, where the test is collected in all women screened and processed routinely in women age 30 years and older. MATERIALS AND METHODS: After a policy change to screen all patients 30 years or older with both Pap smears and high-risk human papillomavirus (HR-HPV), as well as cocollection of HR-HPV in women younger than 30 years, all cytological, HPV, and histological data pertaining to cervical screening was collected retrospectively during a 2-month period. We documented the direct costs of performing these tests and estimated the necessary compliance rate for balanced cost-effectiveness. RESULTS: During the 2-month period, 8,300 women were screened with both Pap smear and HPV cocollection. Of the 'nonnormal' cytological findings, 5% of patients showed either atypical squamous cells (3.5%) or squamous intraepithelial abnormalities (1.5%). An additional 427 (5%) patients had the finding of positive HR-HPV with normal cytology. Six of these patients opted for immediate colposcopy, 2 of which were found to have cervical intraepithelial neoplasia 2. In women age 30 years and older, 900 patients per 1,000 screened would be eligible for a 2-year screening interval based on negative cytology and negative HR-HPV. Based on the direct costs associated with this cohort, no more than 164 women could request screening at an interval shorter than 3 years for the total costs of such a program to equal that of one without HR-HPV cocollection. CONCLUSIONS: By adding HCII collection to the Pap smear for our entire screening cohort, we intended to reduce the number of tests performed, which was impacted by its age distribution. Our findings indicate that at least 736 of the 900 double-negative patients (82%) would have to be screened at no less than 3 years for such a screening paradigm to be cost-effective in managing women 30 years and older.     

p16INK4A immunohistochemistry is superior to HPV in situ hybridization for the detection of high-risk HPV in atypical squamous metaplasia

In situ hybridization (ISH) assays for high-risk human papillomavirus (HR-HPV) and immunohistochemical (IHC) assays for surrogate markers such as p16 can be useful in detecting HR-HPV in cervical dysplasia, but the use of these markers in problematic cervical biopsies has not been well-established. We evaluated 3 chromogenic ISH assays (Ventana INFORM HPVII and HPVIII and DakoCytomation GenPoint) in conjunction with p16 IHC and HPV polymerase chain reaction in a study set consisting of 12 low-grade squamous intraepithelial lesions, 16 high-grade squamous intraepithelial lesions, and 30 benign cervix samples. A test set of 28 cases of atypical squamous metaplasia were also evaluated withVentana HPVIII ISH and p16 IHC. In the study set, the sensitivity of the DakoCytomation ISH assay (which detects HPV subtypes 16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59, and 68) was similar to the Ventana HPVII assay but less than that of the Ventana HPVIII ISH assay (both of which detect HPV subtypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 66) and less than p16 IHC (55.6% vs. 53.6 vs. 69.2% vs. 82.1%). All HPV ISH assays exhibited 100% specificity. p16 reactivity consisted of 2 patterns: focal strong and diffuse strong. Because focal strong p16 reactivity was identified in benign squamous epithelium (6.7% cases) and dysplastic epithelium, it was considered an equivocal result and only diffuse strong reactivity was considered to be specific for the presence of HR-HPV. In the squamous intraepithelial lesions study set, the difference in sensitivity between Ventana HPVIII ISH and p16 was not statistically significant. However, in the atypical squamous metaplasia test set cases, p16 reactivity (focal strong and diffuse strong) was significantly more sensitive than Ventana HPVIII ISH in correlating with the presence of human papillomavirus as detected by polymerase chain reaction (83.3% vs. 33.3% P=0.004). Because focal strong p16 reactivity is less specific, cases with this staining pattern are considered atypical and require further evaluation by other means. Overall, p16 IHC is considered the best candidate for the initial assessment of cervical biopsies that are histologically indeterminate for dysplasia given its wide availability, comparative ease of interpretation, and high sensitivity and specificity.     

Immunochemical assessment of p16 and HPV L1 capsid protein in cervical squamous intraepithelial lesions

The behavior of the cervical squamous intraepithelial lesions cannot be predicted, many of them, particularly of the low grade type, may disappear without treatment. Invasive cervical carcinoma occurs in approximately 10% of the intraepithelial precursor lesions, being strongly associated with HPV infection. The aim of this study was to make a comparative assessment between immunohistochemical and immunocytochemical expression of p16 and L1 HPV capsid protein respectively, in low grade and high grade cervical squamous intraepithelial lesions. MATERIAL AND METHOD: The study involved 20 patients with cytological diagnosis of LSIL/CIN1 (low grade squamous intraepithelial lesion/cervical intraepithelial neoplasia) and HSIL (CIN2 and CIN3) (high grade squamous intraepithelial lesion), which underwent a subsequent cervical biopsy. The conventional smears were evaluated for the immunoexpression of L1HPV protein and the corresponding biopsies for the immunoexpression of p16. RESULTS: The HPV L1 capsid protein was expressed in 46% of LSIL and 24% of HSIL. P16 was positive in 68% of LSIL, 84% of CIN2 and 100% of CIN3. The correlative analysis of p16 status and protein L1HPV expression can be very useful in the assessment of progression risk of cervical squamous intraepithelial lesions.     

Laser treatment of premalignant and malignant squamous cell lesions of the penis.

Thirty men with biopsy-proven premalignant or malignant squamous cell lesions of the penis were treated. All had subclinical aceto-white lesions with histologic evidence for human papilloma virus infection. Nineteen patients had penile intraepithelial neoplasia (PIN I and II) and 11 had squamous cell carcinoma. Of these 11 patients, 6 had noninvasive penile intraepithelial neoplasia--carcinoma in situ (PIN III/Tis)--and 5 had invasive squamous cell carcinoma (4 stage T2 and 1 T3). All were treated with laser: CO2 was used for low-stage lesions, Nd:YAG was used alone or in combination with CO2 laser for more histologically advanced lesions, and KTP/532 was used in one patient with squamous cell carcinoma (Tis). Follow-up in 23 patients for up to 2 years showed that all but 1 (stage T3) remained free from penile malignancy. Appropriate laser therapy for all but deeply invasive (T3) tumors controls local disease, producing results that are clinically equal and cosmetically and functionally far superior to partial penectomy.     

The agreement between cervical abnormalities identified by cytology and detection of high-risk types of human papillomavirus.

OBJECTIVES AND DESIGN: Human papillomavirus (HPV) is causally associated with cervical cancer. Using the Digene Hybrid Capture 2 high-risk HPV test (HC2), we investigated the prevalence of high-risk HPV in cervical specimens, and compared results with those of Papanicolaou (Pap) smears taken concurrently. SUBJECTS AND SETTING: Cervical specimens were obtained from women attending hospitals / community health centres in the Western Cape province of South Africa. They were participating in a case-control study of the association of hormonal contraceptives and invasive cervical cancer. RESULTS: Of 1 491 women tested, 254 (17%) were HPV DNA positive. The age-specific prevalence of HPV was 36/97 (37.1%) in those aged < 30 years, 78/369 (21.1%) in those aged 30 - 39 years, 78/603 (12.9%) in those aged 40 - 49 years and 62/422 (14.7%) in those aged 50 - 59 years. In women with normal cytology the prevalence of HPV was 10.9% (138/1 264); in those with abnormal squamous cells of unknown significance (AS-CUS) it was 30.8% (36/117); in those with low-grade squamous intraepithelial lesions (LSIL) it was 63.2% (36/57), and in those with high-grade squamous intraepithelial lesions (HSIL) it was 83% (44/53). The odds ratio between HPV and HSIL in women aged 40 - 59 years was 57.1 (confidence interval 22.4 - 170.7). CONCLUSIONS: HC2 detected a high prevalence of HPV (17%) in this population. Most women with HSIL (83%) were positive, indicating that HPV testing of AS-CUS women may aid in management. When costs decrease, HC2 could be introduced as an adjunct to Pap smears in identifying women at risk for high-grade cervical disease and could be useful in the maintenance of cervical health in those who remain Pap smear negative.     

Human papillomavirus-associated early vulvar neoplasia investigated by in situ hybridization

Of 21 consecutive cases of early vulvar neoplasia studied at the Istituto Nazionale Tumori of Milan, 62% appeared to be related to papillomavirus infection. This conclusion is the result of the present study by in situ hybridization with DNA probes of human papillomavirus (HPV) 6/11, 16, and 18 and of previous ultrastructural and immunohistochemical investigations. The proportion of cases associated with HPV was 78.5% for those (11/14) with histologic evidence of viral infection and 33% for those without (2/6). HPV 16 was detected in all cases that were positive by in situ hybridization except for one, which showed HPV 6/11 DNA. In one case there was a mixed triple infection for HPV 6/11, 16, and 18. The patient who was positive for HPV 6/11 had a giant condyloma associated with an inguinal lymph node containing a metastatic well-differentiated squamous cell carcinoma. Three cases were positive for papillomavirus internal capsid species-nonspecific antigen (PV-Ag) (with ultrastructural evidence of virions in one of them) and were negative for HPV-DNA hybridization. They appeared to be infected with a type of HPV not identified by the available probes. Three cases, and two sites of two other cases with double infection, were HPV-DNA-positive and PV-Ag-negative. They illustrate the limitation of immunohistochemical investigation in cases with high-grade intraepithelial neoplasia. Six cases of verrucous carcinoma of the vulva were negative for HPV DNA by in situ hybridization.