Detection and typing of human papillomavirus in cervical specimens of Turkish women

The DNA in situ hybridization (DISH) and conventional solution phase polymerase chain reaction (PCR) were applied to identify human papillomavirus (HPV) DNA in cervical specimens of Turkish women. Samples consisted of 21 cervical brushings from pregnant women and 20 paraffin-embedded biopsies from women with condylomatous or dysplasic lesions. It was found that two out of 21 (9.5%) pregnant women were harbouring HPV-DNA detected by PCR. One woman was infected with HPV 16/30's and the other with an unidentified type. As for the biopsy specimens, the rate of HPV-DNA positivity was 30% and 45% by DISH and PCR, respectively. A double infection was observed in more than 50% of the positive cases. Moreover, HPV 18 was never detected. The results indicated that HPV-DNA is rarely present in cytomorphologically normal smears from pregnant women. The PCR method was successfully adapted for HPV typing in clinical lesions which simultaneously contained different HPV sequences.     

Vulvar vestibulitis is rarely associated with human papillomavirus infection types 6, 11, 16, or 18

Vulvar vestibular biopsy specimens from 31 women with clinical and pathologic findings of vulvar vestibulitis were studied using polymerase chain reaction (PCR) for the identification of human papilloma virus (HPV). The PCR technique specifically probed for HPV types 6, 11, 16, and 18. Of the 31 subjects, three were found to have HPV within the biopsy specimens; two had HPV type 11 and one had HPV 16. Five of the 31 cases had histopathologic features of koilocytosis consistent with HPV effect; three of these five were found to have HPV. The findings support the hypothesis that HPV types 6, 11, 16, and 18 are rarely associated with vulvar vestibulitis. The frequencies identified were similar to those seen with control patients. True koilocytosis is the most useful pathologic feature distinguishing HPV-related cases; it is rarely identified in typical vulvar vestibulitis. Nonspecific changes in the vestibular epithelium associated with glycogen effect should not be interpreted as koilocytosis.     

Immunoglobulin G responses against human papillomavirus type 16 virus-like particles in a prospective nonintervention cohort study of women with cervical intraepithelial neoplasia

BACKGROUND: Infection with cancer-linked human papillomavirus (HPV) types such as HPV type 16 (HPV16) is the most important risk factor in the development of cervical cancer. It has been shown that immunoglobulin G (IgG) antibody responses against HPV16 virus-like particles (VLPs) are specifically associated with genital HPV16 infection. PURPOSE: The aim of this study was to determine the temporal relationships between the presence of HPV16 VLP-specific IgGs, HPV16 infection patterns, and the course of premalignant cervical disease. METHODS: Plasma samples from 133 women who had been diagnosed originally with mild to moderate cervical dyskaryosis and enrolled in a prospective non-intervention cohort study conducted in Amsterdam, The Netherlands, from 1991 through 1996 were analyzed for the presence of HPV16 VLP-specific IgGs by use of an enzyme-linked immunosorbent assay. A detailed analysis was performed on 43 women with different HPV16 infection patterns during a follow-up period of 10-34 months. Progression or regression of cervical intraepithelial neoplasia (CIN) lesions was monitored by cytologic and colposcopic testing at intervals of 3-4 months. HPV typing in cervical smears was performed by use of a polymerase chain reaction-based assay. Statistical analysis of the serologic data was performed by use of the Mann-Whitney U test or 2 x 2 table analyses. RESULTS: The presence of HPV16 VLP-specific IgGs in the plasma of the patients was found to be associated with the presence of HPV16 DNA in the cervical smear. Significantly higher proportions of patients with persistent HPV16 infections (i.e., who were polymerase chain reaction positive in three to 11 consecutive tests) than of patients with cleared HPV16 infections were found to be positive for the presence of HPV16 VLP-specific IgGs (18 [69.2%] of 26 versus nine [28.1%] of 32, respectively; P = .003). HPV16 VLP-specific IgGs were consistently detected in all women (n = 11) who were persistently HPV16 DNA positive during follow-up and whose disease ultimately progressed to CIN III (histologically diagnosed severe dysplasia or carcinoma in situ). CONCLUSION: HPV16 VLP-specific IgG responses are present in the plasma of a majority of patients with persistent HPV16 infections and histologically confirmed high-grade lesions but only in a smaller subset of patients with cleared HPV16 infections and either normal cervical histology or low-grade CIN lesions. IMPLICATIONS: These results suggest that HPV16 VLP-specific antibodies are not responsible for the clearance of virally induced CIN lesions but that they might, in patients with persistent HPV16 infections, be indicative of an increased cervical cancer risk.     

Heterogeneity of human papillomavirus DNA in a patient with Bowenoid papulosis that progressed to squamous cell carcinoma

Bowenoid papulosis (BP) of the genitalia, characterized by the histological findings of a squamous cell carcinoma, follows a largely benign clinical course. The detection of oncogenic human papilloma viruses (HPV) from BP points to an aetiological role of these viral infections. A 47-year-old man with multiple genital skin lesions was seen over a 10-year period with the diagnosis of BP. Recently, he attended again with a recurrent genital tumour that was diagnosed as squamous cell carcinoma. His genital lesions progressed and became polymorphic in appearance, from a wart-like tumour to a reddish invasive plaque. To screen for the presence of different HPV sequences from different skin lesions and to correlate each HPV type with distinct clinical manifestations, polymerase chain reaction and single-strand conformational polymorphism (PCR-SSCP) were performed. PCR-SSCP revealed the presence of several types of HPV from different genital lesions. Sequencing results disclosed that he had a mixed infection of HPV6b, HPV16, HPV18 and HPV33, respectively. Interestingly, the clinical findings were fairly well correlated with the oncogenic potential of HPV found from each lesion.     

Prevalence of human papillomavirus infection and HPV DNA among male partners of Israeli women with genital premalignant and human papillomavirus lesions

The role of the males who are sexual partners of females with genital human papillomavirus (HPV) infection and premalignant lesions is explored in the present study. Within a period of 3 years, 391 females with genital premalignant and HPV-associated lesions were examined and treated at the Cervical Pathology Unit of the Tel Aviv Medical Center. The male partners of all the women were asked to attend this unit, and 322 of them responded. All participants underwent colposcopic examination of the anogenital area followed by colposcopically guided biopsies from the most representative lesions, when present, part of which included in situ hybridization (ISH) of HPV DNA sequences 6/11 and 16/18. The histological prevalence of HPV among the male partners was 86.6% (185 of 213 biopsies). Of the 48 couples who had ISH evaluations, the ISH could not identify any copy of HPV DNA in 58.3% of the males (28 cases) and 41.6% of the females (20 cases). Among the males, HPV 6/11 and 16/18 were found in 17 (35.4%) and 3 cases (6.2%), respectively, and among the females there were 23 (48.0%) and 5 cases (10.4%), respectively. Correlation of HPV DNA sequences 6/11 and 16/18 between the couples was found in six (12.5%) and in one (2.0%), respectively. These data do not support a direct contamination by the current male partner. The question of treating the male partner of a woman with genital HPV and premalignant lesions remains to be evaluated.     

A comparison of human papillomavirus detection rates by dot blot assay from smear and biopsy specimens with regard to human papillomavirus type and histologic diagnosis

Colposcopic biopsy and cervical smear sampling techniques for human papillomavirus (HPV) DNA dot hybridization were compared to reveal differences related to the level of the histopathologic detection of HPV type 16. The authors used a previously published dot blot assay to analyze 814 pairs of concurrent biopsy and smear DNA specimens for the presence of DNA of HPV 6, 11, 16, and 18. The overall HPV detection rate was 38%, the most prevalent type being HPV 16 (39% of all HPV-positive cases). In detection and typing of HPV DNA, a 81% concordance (658 of 814 pairs) was noted between the smear and biopsy specimens, with a significant correlation in detection of any of the HPV types in the specimens (kappa, .609). The rate of smear-negative cases among all biopsy-positive cases was similar for HPV 11 and HPV 16 (41% and 42%, respectively). Further analysis of distribution of the smear-negative and biopsy-positive cases among different histopathologic levels of disease showed no significant difference between neoplastic and nonneoplastic lesions for either virus type. In 56 cases, only the smear specimen was positive for DNA of the studied HPV types. Both biopsy and smear specimens should be used for HPV detection in cervical dysplasias.     

Cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV) infection

Many studies have shown a strong correlation between CIN and HPV infection. Molecular biology has allowed identification of types of HPV which seem to be connected, more frequently than others, to dysplastic lesions. Physical state of HPV-genome seems to play an important role in the development of cervical cancer. In this study the HPV-genome has been searched in tissue specimens obtained from 34 women affected by CIN II and III. All patients underwent laser conization. Immediately before treatment, colposcopically directed biopsies of the cervical lesion and of the areas with no colposcopically apparent disease were taken and on these samples, HPV-DNA has been searched, isolated and analysed for HPV types and physical state. Histologic examination on cones showed 6 cases of CIN II (3 with HPV), 24 cases of CIN III (14 with HPV), 1 microinvasive carcinoma and 3 with no residual lesion. Southern blot analysis detected HPV-DNA in 4 cases of CIN II (16.7%) and in 20 cases of CIN III (70.6%). In 50% of CIN II and 85% of CIN III HPV 16 DNA has been found and in the remaining 50% of CIN II and 15% of CIN III HPV 31 DNA has been detected. All CIN II and 14 cases of CIN III showed episomal HPV-DNA. Integrated HPV-DNA has been found in 3 cases of CIN III and the other 3 cases of CIN III showed both integrated and episomal HPV-genome. Integrated form has been noticed only for HPV 16 type. In no case of colposcopically normal tissue has HPV-DNA been found. These data seem to confirm the strong correlation between HPV 16 type, which often has integrated form, and CIN III strengthening the hypothesis of its potential oncogenic action.     

Intraepithelial neoplasia of the vulva

Intraepithelial neoplasia of the vulva is being seen with increasing frequency. Awareness of this should prompt the clinician to carefully inspect the vulva on all patients. Reports strongly suggest a relationship between infection with human papillomavirus and vulvar intraepithelial neoplasia. The frequency with which this disease progresses to invasive carcinoma is unknown at present. However, it is obvious that it does occur. Both the warty and basaloid types of vulvar intraepithelial neoplasia are associated with HPV infection and are often associated with invasive squamous cell carcinoma of the vulva demonstrating similar morphologic characteristics. These changes are seen more often in younger women who smoke than in the older nonsmoking woman whose lesions do not appear to be HPV related. Both local excision and the carbon dioxide laser are effective for treating vulvar intraepithelial neoplasia. The choice of which approach to take depends upon the location and size of the lesion or lesions. Whichever approach is utilized, preservation of the normal vulvar anatomy and function are of paramount importance.     

Detection of human papillomavirus DNA by PCR in high-risk women. Validation of a protocol

OBJECTIVE: To validate a protocol for HPV DNA detection using PCR (polymerase chain reaction). METHOD: HPV was investigated in cervical exfoliative specimens from 93 women at high risk for HPV infection Blind comparisons of HPV DNA detection using two PCR protocols were carried out in our laboratory and a widely accepted reference laboratory. RESULTS: HPV DNA prevalence varied according to the different protocols. A good agreement with the reference protocol was reached when a reduction of the cellular amount for DNA extraction was carried out. The prevalence of HPV DNA in this population was 50.5%. All cases with dysplasia were HPV DNA positive. The HPV type distribution was as follows: 29.8% HPV 16, 17% HPV 33, 12.7% HPV 11/6, 12.7%, HPV 18, 23.4% HPV 31, 3.6% HPV 39 y 4.3% HPV 51. An underestimation of the prevalence of HPV 51 was detected by our procedure in relation to the reference laboratory. CONCLUSIONS: HPV DNA detection by PCR may increase with simple protocol modifications. Regular validation studies are important to reach good sensitivity levels.     

Cervical intraepithelial neoplasia and human papillomavirus related lesions of the genital tract in HIV positive and negative women

Two hundred and twenty one women at high risk for HIV (intravenous drug users and/or those with infected partners) were investigated, through a self-filled questionnaire and gynaecological examination, to define the relationship between genital Human Papilloma Virus (HPV) infections, preneoplastic cervical intraepithelial lesions (CIN) and behavioural risk factors. In the 121 HIV positive women, 58 (47%) had HPV lesions at colposcopic and/or cytologic examination and, out of these 58, 23 (40%) had CIN 1, CIN 2 or CIN 3. Six out of the 16 cases with CIN 1 and CIN 2 (37%) followed-up showed a rapid progression of the lesion to CIN 3; in 3 women the interval was 6 months, in the other 3 about 12 months. Only 5 (7%) of the remaining 66 women without HPV lesions had a CIN lesion, with an obviously significant difference on comparison with HPV positive subjects. Sixty two women out of the 121 (52%) had a previous diagnosis of condylomata. In the 100 HIV negative women, 23 (23%) had HPV lesions and, among these 23, 6 (26%) had CIN 1, CIN 2 or CIN 3; 1 of them had rapid progression from CIN 1 to CIN 3 within a year. Only 5 (3%) without HPV infection showed any kind of CIN. 33 women out of 100 (33%) had a previous clinical history of condylomata. Our findings strongly suggest that HIV infection is associated with HPV lesions and that cervical cytological abnormalities develop in this situation. There is a need for short interval cytological and colposcopic follow-up for women at high risk of HIV infection.     

Prevalence of human papillomavirus types 16 and 18 in penile carcinoma: a study of 41 cases using PCR

AIMS: To determine retrospectively the prevalence of human papillomavirus (HPV) types 16 and 18 in penile carcinomas. METHODS: Forty one surgically resected penile carcinomas from the archives at Queen Mary Hospital, Hong Kong, were reviewed and classified into verrucous carcinoma, and well, moderately, and poorly differentiated squamous cell carcinomas. Paraffin wax embedded tumour tissue was sectioned and analysed for HPV 16 and HPV 18 using the polymerase chain reaction with type specific internal probes. RESULTS: There were seven verrucous carcinomas, and 11 well, 17 moderately, and six poorly differentiated squamous cell carcinomas. Six of the 41 (15%) patients had penile carcinoma containing HPV 16 or HPV 18 DNA, or both, with HPV 16 found in four (10%) and HPV 18 in four (10%). The mean ages of HPV positive and HPV negative groups of patients were 68.5 and 57.6 years, respectively (p < 0.05). None of the seven verrucous and 11 well differentiated squamous cell carcinomas was positive for HPV. The mean age of patients who had these carcinomas was 52.4 years. As a group, these low grade carcinomas occurred in patients younger by more than a decade than those who had carcinomas of the higher grades (mean age 64.4 years; p < 0.01). CONCLUSIONS: Penile carcinomas had much lower rates of infection by HPV 16 or HPV 18 than cervical carcinomas in this Hong Kong population. Based on our findings and on data collated from published findings, it is concluded that penile verrucous carcinomas are not associated with HPV 16 and HPV 18. The overall low prevalence of HPV 16 and HPV 18 in penile carcinomas suggests that other HPV types might be important in the pathogenesis of these tumours.     

Issues in the management of human papillomavirus genital disease

Human papillomavirus (HPV) infects epithelial cells at a variety of anatomic sites. Of the more than 80 types of this virus, approximately one third infect genital tissue. Genital infection can be clinical (warts), subclinical (abnormal Papanicolaou [Pap] smears or lesions visible only with magnification and application of acetic acid) or latent (infection with apparently normal tissue). Recent research has revealed a clear association between genital warts and HPV types 6 and 11, and between cervical cancer and HPV types 16, 18 and others. Women with genital warts who have normal Pap smears do not need colposcopy. All available therapies are suboptimal because HPV is not eradicated by treatment. However, the active disease expression can be eliminated by treatment. The approach to treatment will depend on each patient's personal characteristics and preferences.     

Evaluation of argyrophilic nucleolar organizer regions (AgNORs) in oral carcinomas in relation to human papillomavirus infection and cytokinetics

The numbers of argyrophilic nucleolar organizer regions (AgNORs) were quantified in oral carcinomas (n = 39) with or without human papillomavirus (HPV) infection. The AgNOR counts of the HPV-positive samples (7.15 +/- 2.13) were not significantly (P = 0.09) higher than those of the HPV-negative ones (6.16 +/- 1.89). Furthermore, the lesions infected with multiple HPV types had greater counts than those with HPV type 16/18 infection alone. Significant differences were observed between the mean counts of the poorly (10.50 +/- 0.54), moderately (7.31 +/- 1.07) and well- (5.12 +/- 0.85) differentiated carcinomas. The mean AgNOR numbers in the oral carcinomas at TNM stages III/IV were found to be significantly (P < 0.01) higher than the numbers in corresponding stage II lesions. Cytokinetics of the lesions assessed by the bromodeoxyuridine (Brdu) labelling index (LI%) showed a linear correlation (r = 0.91; P < 0.0001) with their respective mean AgNOR counts.     

Genomic variation of human papillomavirus type 16 and risk for high grade cervical intraepithelial neoplasia

BACKGROUND: Epidemiologic studies have demonstrated strong and consistent associations between the detection of human papillomavirus (HPV) type 16 DNA and the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. However, HPV16 is also the most common type of HPV in the normal population, and only a minority of women with HPV16 infection develop cervical cancer. Studies of genomic heterogeneity in HPV16 have demonstrated the presence of multiple variant forms in all human populations examined to date. It is conceivable that the natural variants of HPV16 in a given population may not have the same biologic behavior. PURPOSE: This study was designed to determine the association between natural variants of HPV16 and the risk of biopsy-confirmed CIN 2 or 3, the most important precancerous lesions of the uterine cervix. METHODS: Prospective studies were conducted among 1) women attending a university and 2) women presenting to a sexually transmitted disease clinic. Subjects were eligible for inclusion in this investigation if the initial cytologic findings did not reveal CIN 2-3 and HPV16 DNA was detected by means of a polymerase chain reaction (PCR)-based method in one or more cervical or vulvovaginal samples. Eligible subjects were followed every 4 months with cervical Pap smears and colposcopic examinations. Women were referred for biopsy if cytology or colposcopy suggested CIN 2-3. Two groups of HPV16 variants, prototype-like and nonprototype-like, were determined by means of single-strand conformation polymorphism (SSCP) analysis of PCR products from the noncoding region of the viral genome. Representative SSCP patterns from HPV16 variants were further characterized by direct DNA sequencing of the PCR products. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox regression analysis. RESULTS: Prototype-like variants accounted for 79% of the HPV16 detected in university students and 86% of the virus detected in patients presenting to the sexually transmitted disease clinic. CIN 2-3 was confirmed by biopsy in nine of 57 HPV16-positive women attending the university and in 10 of 66 HPV16-positive women presenting to the sexually transmitted disease clinic. Among university students, those with HPV16 nonprototype-like variants were 6.5 (95% CI = 1.6-27.2) times more likely to develop CIN 2-3 than those with prototype-like variants. A similar association was observed among women presenting to the sexually transmitted disease clinic (RR = 4.5; 95% CI = 0.9-23.8). CONCLUSIONS: This study suggests that the risk of developing CIN 2-3 is not the same with all variants of HPV16 and that nonprototype-like variants confer a greater risk compared with prototype-like variants. The important genomic differences underlying this increased risk of CIN 2-3 remain to be determined.     

Oral cancer risk in relation to sexual history and evidence of human papillomavirus infection

BACKGROUND: Experimental models and analyses of human tumors suggest that oncogenic, sexually transmittable human papillomaviruses (HPVs) are etiologic factors in the development of oral squamous cell carcinoma (SCC). We conducted a population-based, case-control study to determine whether the risk of this cancer is related to HPV infection and sexual history factors. METHODS: Case subjects (n = 284) were 18-65-year-old residents of three counties in western Washington State who were newly diagnosed with oral SCC from 1990 through 1995. Control subjects (n = 477) similar in age and sex were selected from the general population. Serum samples were tested for HPV type 16 capsid antibodies. Exfoliated oral tissue collected from case and control subjects and tumor tissue from case subjects were tested for HPV DNA. Odds ratios (ORs) were calculated after adjusting for age, sex, cigarette smoking, and alcohol consumption. RESULTS: Among males only, oral SCC risk increased with self-reported decreasing age at first intercourse, increasing number of sex partners, and a history of genital warts. Approximately 26% of the tumors in case subjects contained HPV DNA; 16.5% of the tumors contained HPV type 16 DNA. The prevalence of oncogenic HPV types in exfoliated oral tissue was similar in case and control subjects. The ORs for HPV type 16 capsid seropositivity were 2.3 (95% confidence interval [CI] = 1.6-3.3) for all oral SCCs and 6.8 (95% CI = 3.0-15.2) for oral SCCs containing HPV type 16 DNA. The joint association of cigarette smoking and HPV type 16 capsid seropositivity with oral SCC (OR = 8.5; 95% CI = 5.1-14.4) was stronger than predicted from the sum of individual associations with current smoking (OR = 3.2; 95% CI = 2.0-5.2) and seropositivity (OR = 1.7; 95% CI = 1.1-2.6). CONCLUSIONS: HPV type 16 infection may contribute to the development of a small proportion of oral SCCs in this population, most likely in combination with cigarette smoking.     

Occurrence of human papillomavirus infection in cervical intraepithelial neoplasia. A retrospective histopathological study of 317 cases treated by laser conization

The aim of the study was to compare the histological outcome of the cone specimens with the diagnoses of the preoperative biopsies, to assess the distribution of histological features consistent with human papillomavirus (HPV) infection and, finally, to analyse the impact of cellular HPV features on classification of cervical intraepithelial neoplasia (CIN). The study comprised a population of 317 women treated for CIN by laser conization during the period 1983-85. A total of 634 cervical specimens (317 preoperative biopsies and their corresponding cones) were studied retrospectively for CIN classification and examined for morphological signs of HPV infection. For presentation of the results, we used a modified terminology for CIN. Low-grade (LG) CIN included borderline lesions and CIN I, while high-grade (HG) CIN included CIN II and CIN III. The blinded histopathological review revealed HG CIN both in the preoperative biopsies and the cones in 71% of the cases. LG CIN or benign lesions were found in the preoperative biopsies and their corresponding cone specimens in 6% of the study population. HPV features were present in 65% of the preoperative biopsies, and were most prevalent in women under 29 years of age (p < 0.001). Thirteen percent of the total biopsy material was downgraded. The downgrading was most prevalent among original CIN II (p = 0.009) and HPV-negative biopsies (p < 0.001). This study demonstrates that CIN lesions are frequently associated with HPV features, which are significantly more prevalent in the youngest women. Concomitant HPV features do not influence the CIN classification.     

Perinatal transmission and maternal risks of human papillomavirus infection

We conducted a prospective study to investigate whether human papillomavirus (HPV) could be vertically transmitted to neonates. Pregnant women (N = 203) were tested for HPV DNA infection during the third trimester and again during labor prior to delivery. Their newborns (N = 203) were tested 1 to 3 days after delivery. Among the mothers, 12.3% (N = 25/203) typed HPV positive at either or both maternal specimen collection periods, whereas only 1.0% of the neonates (N = 2/203) typed positive. This low transmission rate may be due in part to the fact that 65% of mothers who were HPV positive during the third trimester tested HPV negative by labor/delivery. The higher frequency of risks associated with maternal HPV infection were similar to those found in studies of cervical dysplasia and cancer: younger age at first intercourse and first pregnancy, number of sexual partners, and longer duration in use of oral contraceptives. In addition, those who were past smokers and had a shorter recency and latency period in smoking were more likely to be detected with HPV.     

Human papillomavirus genotype as a major determinant of the course of cervical cancer

PURPOSE: To determine whether the prognosis of invasive cancers of the uterine cervix is related to the type of human papillomavirus (HPV) associated with the tumor. PATIENTS AND METHODS: Two hundred ninety-seven patients with invasive cervical cancer were prospectively registered from 1986 to 1994. HPV typing was performed on DNA extracted from frozen tumor specimens by means of Southern blot hybridization (SBH) and polymerase chain reaction (PCR) techniques. The median follow-up was 38 months. RESULTS: HPV sequences were detected in 246 patients (83%): 150 patients had HPV16, 31 patients had HPV18, and 14 patients had one of the intermediate-oncogenic-risk HPV types (HPV31, 33, 35, 52, 58). In 51 patients, HPV type remained undetermined, and in 51 patients, no viral sequences were found. No significant associations were observed between virologic data and tumor stage or node status. The 5-year disease-free survival (DFS) rate was 100% for patients with intermediate-risk HPV-associated tumors, 58% for patients with HPV16-positive tumors, and 38% for patients with HPV18-positive tumors (P = .02). In multivariate analysis, patients with HPV18-associated tumors had a relative risk (RR) of death 2.4 times greater (95% confidence interval [CI], 1.29-4.59) than that for patients with HPV16, and 4.4 times greater (95% CI, 3.48-5.32) than that for patients with a tumor associated with a viral type different from HPV16/18. CONCLUSION: The prognosis for invasive cancers of the uterine cervix is dependent on the oncogenic potential of the associated HPV type. HPV typing may provide a prognostic indicator for individual patients and is of potential use in defining specific therapies against HPV-harboring tumor cells.     

Usefulness of hybrid capture HPV DNA assay as a diagnostic tool for human papillomavirus infection

The purpose of this study was to determine the usefulness of the hybrid capture HPV DNA assay, a new nonradioactive solution hybridization assay, as a diagnostic tool for human papillomavirus infection. In a total of 234 women, samples for the hybrid capture assay and polymerase chain reaction (PCR) assay were obtained by wiping a swab across the cervix and external os (either a Dacron swab or a cotton swab was used). The papanicolaou smear test (Pap smear) was carried out on all 234 women. Tissue samples for biopsy were obtained by colposcopy from 118 of the women. Fisher exact test was used for statistical analyses. Using the hybrid capture assay, HPV DNA of high- and intermediate-oncogenic-risk type was detected in 23 (13.9%) of 166 samples from women with Pap smear Class I or II, and 48 (70.6%) of 68 with Pap smear Class III, IV or V (p < 0.0001). The HPV DNA type was detected in 18 (29.0%) of 62 samples from those with no evidence of cervical intraepithelial neoplasia and 44 (78.6%) of 56 with cervical intraepithelial neoplasia or squamous cell carcinoma (p < 0.0001). Correlation of the test results between the hybrid capture test and PCR was determined by using the 217 samples in which both test results were available (PCR test results were not obtainable in 17 samples. When PCR is set as a gold standard, the hybrid capture test has high sensitivity (74.6%) and specificity (92.7%). These findings suggest that the hybrid capture HPV DNA assay is a useful method for diagnosing HPV infection in the clinic.