An observational study of women with positive HPV-DNA tests and normal cytology and colposcopy

PURPOSE: High risk human papillomaviruses (HPV) are implicated in the aetiology of malignant cervical disease. The usefulness of HPV DNA tests in identifying women at risk of cervical cancer as an adjunct to cervical cytology is under evaluation. Patients and METHODS: This is a retrospective analysis of 47 women positive for high risk HPV but with negative cytology and negative colposcopy at the start of the study. Women were observed for three years or more (in 96% cases) using six-monthly combined HPV DNA tests, cytological and colposcopic evaluation. RESULTS: At the end of follow-up, 29/47 (62%) women were still positive for high risk HPV, 45/47 (96%) women had normal cytology and 47/47 (100%) women continued to have normal colposcopy. CONCLUSIONS: Normal colposcopy has an excellent negative predictive value for HPV positive women with normal cytology. These women can be safely screened cytologically on a three-yearly basis.     

Human papillomavirus testing in the clinical laboratory. Part I: squamous lesions of the cervix

The aim of this study was twofold: (1) to evaluate the contribution of viral (HPV) testing for improving the sensitivity of cervical cytology and (2) to correlate HPV types with the histology of the detected cervical cancer precursors, particularly the low-grade, CIN I variant. We used the dot blot hybridization technique (ViraPap) and polymerase chain reaction (PCR) in 63 women referred to our colposcopy clinic for evaluation of an abnormal Pap test. Histopathologic samples obtained by multiple colposcope-directed punch biopsies were used for a diagnostic gold standard. Among the 53 women with histologically proven CIN, precolposcopy cytology was positive in 38 (72%) compared to 53% and 60% HPV positivity by ViraPap and PCR, respectively (p less than 0.01). When the yields of ViraPap/PCR and cytology were combined, however, the detection rate of CIN was 91%, a significant improvement over cytology alone (p less than 0.02). HPV DNA was found either by ViraPap or PCR in 45 of 63 (71%) biopsy specimens, and 37 of 38 (97%) HPV-positive CIN, including the low-grade CIN I variant, contained oncogenic HPV types. HPV type 16 was present in 22 of 38 (58%) CIN lesions and mixed with HPV 6/11, 18, or the 30s group in 6 of 38 (16%) of the cases. HPV 6/11 alone was found only in 1 case of CIN I (2.7%). HPV testing by molecular technology increases the sensitivity of cytology.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of DAPK gene methylation and HPV and EBV infection in cervical cells from patients with normal cytology and colposcopy

Objective Evaluation of promoter methylation of the death-associated protein kinase (DAPK) gene and HPV and EBV infections in cervical cells from patients with normal cytology and colposcopy. Study design Twenty women, who had been patients at the Institute of Gynecology of the Federal University of Rio de Janeiro (UFRJ) for routine examinations and who showed normal cytology and colposcopy, were selected for this work. Cervical brushings were used for DNA extraction, and the analysis of methylation patterns of the DAPK gene was done through chemical modification with sodium bisulfite. Analysis of viral infection was done using polymerase chain reaction (PCR). Results Of the 20 patients studied, six (30%) presented methylation of the DAPK gene, five (25%) presented infection with EBV and three (15%) presented coinfection with HPV/EBV. Associating methylation with viral infection, we found methylated DAPK in one patient (16%) with EBV, in two patients (33%) with co-infection and in three patients (50%) with no viral infection. Conclusions In the present study, we verified, for the first time, the methylation pattern of the DAPK gene in cervical smears from patients with normal cytology and colposcopy. The results also showed the presence of viral infections in these patients. EBV infection, irrespective of whether associated with HPV or not, may contribute to cervical carcinogenesis as a cofactor. Methylation of the DAPK gene is associated with cell transformation, suggesting that DAPK methylation might be an important marker for the development of cervical epithelial neoplasias.     

Colposcopy: the value of HPV testing in clinical practice

The indications for colposcopy have changed recently because of the new Bethesda terminology, the introduction of HPV testing in clinical practice, and the latest consensus guidelines on management of patients with an abnormal cervical cytological test. Colposcopy remains the reference technique to assess patients with abnormal cytological test results, especially those with ASC-H, LSIL, HSIL, and AGC. In women with an ASC-US result, colposcopic examination of only those who test positive for high-risk HPV increases the specificity of the technique. When liquid-based cytology is used, HPV DNA testing is the preferred approach in these women. In primary screening using combined cytology and HPV DNA testing in women over the age of 30, colposcopy is indicated in patients with normal cytology and two HR HPV DNA positive tests performed at a nine month interval. For the follow up of untreated patients with ASC-US/LSIL and CIN I, colposcopy carried out at one year after a single HR HPV DNA positive test is as sensitive as colposcopy after two or three abnormal cytology tests. After excision or conization in patients with high-grade CIN, colposcopy after a single HR HPV DNA positive test is as sensitive as cytology testing and colposcopy at six months. Therapeutic decisions must not be based solely on the results of HPV DNA testing except in specific cases.     

The use of human papillomavirus typing in detection of cervical neoplasia in Recife (Brazil)

Abstract. Lorenzato F, Ho L, Terry G, Singer A, Santos LC, de Lucena Batista R, Lubambo T. The use of human papillomavirus in detection of cervical neoplasia in Recife (Brazil).
High risk types of human papillomavirus (HR-HPV) play a major role in cervical cancer oncogenesis. This study aims to evaluate the efficacy of HPV detection and typing as a means of identifying cervical neoplasia in a high risk population. A management algorithm for implementation of HPV detection in clinical practice is also proposed. A nested case-control within a cohort study was undertaken in Recife (Brazil). All 479 participants had cervical scrapes collected for HPV detection followed by colposcopy. Samples were blindly analyzed by polymerase chain reaction (PCR) and typed by restriction fragment length polymorphism (RFLP).
HPV detection by PCR and typing with RFLP cost US$ 4.92 per woman screened in this study and is significantly better than cytology in identifying women at risk of developing cervical cancer ( P = 0.0001). Women who tested positive for HR-HPV had over 35-fold increased risk of having high grade squamous intraepithelial lesion (HSIL) or cervical cancer, although this does not necessarily translate into the same risk rate for women with latent HPV infection developing major cervical neoplasia. HPV typing offers 90% sensitivity and 85% specificity for cervical cancer detection. In combination with cytology it provides a negative predictive value of 99.4% and a sensitivity of over 96% for detection of HSIL and cervical cancer.
We conclude that HPV typing is an inexpensive and effective method for identification of cervical neoplasia and women at risk of developing it. It improves quality control for both false negative and false positive cytology results. Routine screening intervals could safely be increased to 3–5 years, decreasing anxiety and socio-economic inconveniences.     

Human papillomavirus cervical infection and associated risk factors in a region of Argentina with a high incidence of cervical carcinoma.

OBJECTIVE: To assess the prevalence and potential risk factors associated with human papillomavirus (HPV) cervical infection among women residing in a region of northeastern Argentina with a high incidence of cervical cancer. METHODS: A case-control study of 330 women participating in a cervical cytological screening program conducted in Posadas city, Misiones, Argentina, from February 1997 to November 1998 was carried out. Standardized questionnaires were administered, and clinical examination including colposcopy was performed. Fresh endocervical specimens for HPV DNA detection by generic polymerase chain reaction were collected and the products typed by dot-blot hybridization. RESULTS: Human papillomavirus DNA was found in 61% of samples analyzed (185/301). Samples with normal cytology had a 43% infection rate (85/199), while those classified as low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, and invasive cervical carcinoma had an infection rate of 96% (53/55), 100% (29/29), and 100% (18/18), respectively. Human papillomavirus typing showed a 64% (118/185) prevalence of type 16 among all the infected population analyzed; type 16 was detected among 49% (42/85) of infected samples with normal cytology and in an average of 74% (74/100) with abnormal cytology. Sexual behavior, residence in southern Paraguay, and history of a previous sexually transmitted diseases were the main risk factors associated with high-grade cervical lesions. CONCLUSIONS: An elevated prevalence of HPV infection was detected in this population, which also has a high incidence of cervical cancer. The broad distribution of high-risk HPV type 16 in women with normal cytology and colposcopy suggests that viral infection is an important determinant of regional cancer incidence.     

High risk human papillomavirus in women with normal cervical cytology prior to the development of abnormal cytology and colposcopy

Objective To study the significance of the presence of high risk human papillomavirus (HPV) in women with initially normal cervical cytology for the development of abnormal cytology and an abnormal colposcopic impression.
Design Prospective, observational study
Participants and methods Sixty-eight women with cytomorphologically normal smears and at least one positive HPV test result were evaluated every six months by cytology, colposcopy and HPV testing. The endpoint of the study was abnormal cervical cytology.
Results The median time of follow up from the first positive HPV test was 34 months. A total of 17 women developed abnormal cytology, of whom 16 (94%) had persistence of a high risk HPV infection. Women with persistent high risk HPV were more likely to develop abnormal cervical cytology than women without high risk HPV (hazard ratio 28.2, 95% CI 3.72–215.2); they also had an increased risk of developing an abnormal colposcopic impression (hazard ratio 4.4, 95% CI 1.69–11.7). Among the 17 women with abnormal cytology, high grade dysplasia was histopathologically demonstrated in eight women.
Conclusion Persistent presence of high risk HPV in normal cervical smears is associated with a significantly increased risk of developing abnormal cytology and to a lesser degree with developing an abnormal colposcopic impression.     

Prevalence of high-risk human papillomavirus (HR-HPV) types 16 and 18 in healthy women with cytologically negative Pap smear

OBJECTIVE: To study the prevalence of high-risk human papillomavirus (HR-HPV) types 16 and 18 in healthy women with negative Pap smears in identifying women with underlying cervical squamous intra-epithelial (SIL) lesions. METHODS: A total of 3300 women who were attending the Gynecology OPD of Lok Nayak Hospital, one of the major government tertiary hospitals in New Delhi, were screened during a 1-year study period, and 2079 (63%) of them were found to have cytologically negative Pap smear with inflammation and the rest (37%) also had negative Pap report but without inflammation. Hundred and sixty of these sexually active women aged between 20 and 60 years were randomly selected, and were investigated by colposcopy and a guided biopsy was done wherever required. HPV types 16 and 18 DNA was detected in scraped cervical cells from all women using type-specific primers in polymerase chain reaction (PCR). RESULTS: The high-risk HPV (type 16 and 18) prevalence by PCR was found to be 10% (16/160). Histopathological findings were obtained in 123 women, out of which 15 had LSIL and four had HSIL. High-risk HPV types 16/18 could be detected in nine out of these 19 (47.3%) squamous intra-epithelial lesions (p < 0.00008) which includes two out of the four women (50%) having HSIL, while only seven out of 104 (6.7%) of the subjects with normal (negative) Pap reports (p = 0.03) had infection of high-risk HPV. CONCLUSION: The results indicate that about 10% of women who show a negative Pap smear, but have inflammation are positive for high-risk HPV types 16/18 and about 15% harbor squamous intra-epithelial lesions. It is suggested that high-risk HPV detection can be utilized as an adjunct to routine cytology screening programs to identify 'high risk' women who have concurrently negative Pap smears but may harbor oncogenic HPV infection and/or more likely to develop CIN lesions.     

Screening of premalignant cervical lesions for HPV 16 DNA by sandwich and in situ hybridization techniques

A series of 97 cervical smears and 69 directed punch biopsies derived from 84 consecutive women prospectively followed-up for cervical HPV (human papillomavirus) infections were studied using the sandwich hybridization and in situ hybridization techniques with HPV 16 DNA probes. The aim was to test the sensitivity and applicability of these two techniques in routine diagnosis of cervical HPV infections from smears. As a measure of specimen adequacy, the number of cells recovered in the cervical scrape was determined along with HPV 16 DNA in the sandwich hybridization test using human pro-alpha 2(I)-collagen gene probe. CIN (cervical intraepithelial neoplasia) was suggested in 56% of the patients by the Pap smear, and disclosed in 65% of the biopsies. HPV 16 DNA was present in 57% of cervical scrapes consistent with CIN, i.e., were of Pap smear classes III or IV. Forty percent of the scrapes not suggestive of CIN, i.e., Pap smear classes I or II, also contained HPV 16 DNA. The detection rate for HPV 16 DNA of the sandwich hybridization method was 89% of that of the in situ method in adequate scrapes, but only 43% in cell-poor specimens. The number of HPV 16 DNA-positive scrapes as compared with the total number of diagnoses obtained by studying also the biopsies was 31/36 (69 patients). The results indicate that the cervical scrape as a noninvasive specimen is applicable for screening of cervical HPV infections, and it can be studied with acceptable sensitivity by the rapid sandwich hybridization technique. However, if a punch biopsy is indicated it should be studied using the in situ hybridization technique that allows more sensitive detection of HPV DNA than any other hybridization method and enables the analysis of several HPV types in the same sample instead of only one HPV type in the scrapes.     

Human papillomavirus (HPV) DNA detection in self-collected urine

OBJECTIVE: Non-invasive sampling of human genitals to identify high-risk individuals with subclinical oncogenic HPV infection remains a challenge. The study was designed to see if self-collected urine can be used as a simple, non-invasive sampling for screening HPV, particularly for screening/monitoring general population or young adolescents or infants, if they are to be immunized by HPV vaccines. METHOD: Self-collected urine samples from 100 sexually unexposed college going girls and cervical scrapes from 104 normal healthy sexually active married women were used in this study. Additionally, a group of 55 women were recruited for collecting first urine and later scraped cervical cells to validate urine sampling by directly comparing HPV positivity between the two types of biological specimens. A dry 'paper smear' method for specimen collection and a simple single tube protocol was employed for PCR detection of HPV infection. RESULTS: Out of 100 sexually inexperienced college going girls, only 6 (6%) were positive for HPV infection as revealed by L1 consensus primer and 4 (4%) of them were positive for HPV 16 but none was found positive for HPV 18 DNA. Out of 104 sexually active married women who were cytologically reported as negative by Pap test, 11 (10.5%) were found HPV positive and 7 (6.7%) of them had infection of high-risk HPV type 16. Both urine and later cervical scrapes from a group of 55 women collected as dry 'paper smear' showed perfect matching positivity for HPV between urine and cervical scrape. CONCLUSIONS: The use of urine coupled with its dry collection as 'paper smear' facilitating their easy transport, storage and direct PCR detection of HPV DNA opens up an alternative non-invasive approach for population screening of HPV infection, at least in such cases as children and infants in whom invasive samples are difficult to obtain.     

Detection of human papillomavirus (HVP) 16/18 infections of the vaginal uterine cervix in females before and following conisation

280 women have been tested by FISH to detect an HPV 16/18-infection of the portio uteri. In a group of 133 women treated by conisation (all with a history of abnormal smear and colposcopy) 67 (50%) were positive for HPV 16/18 DNA before the operation. Follow up examinations of 20 cases with positive HPV 16/18 test before conisation, showed 6 and 12 months after operation only in 3 cases a persistence of HPV 16/18 infection. Only 5 (6.4%) of 78 women with a history of conisation and diagnosis CIN III some years ago were positive for HPV 16/18. In another group of 47 elderly women, treated by abrasio and with normal cervical histology, only 5 (10.6%) had a positive result in the HPV 16/18 FISH-test. 2 (10.6%) of 22 women with normal smear and colposcopy (control group) were positive for HPV 16/18.     

Human papillomavirus infection and cervical disease in human immunodeficiency virus-1-infected women

OBJECTIVE: To report on the natural history of high-risk human papillomavirus (HPV) infection and cervical disease in human immunodeficiency virus (HIV)-1-infected women living in Cape Town, South Africa. METHODS: This was a prospective study of 400 untreated, HIV-1-infected women who underwent high-risk HPV DNA testing, cytology, colposcopy, histology, and CD4 count testing every 6 months for 36 months. Human immunodeficiency virus viral loads and HPV type distribution were determined at entry and after 18 months. RESULTS: Sixty-eight percent of the women were high-risk HPV DNA positive at entry, 35% had a cytologic diagnosis of low-grade squamous intraepithelial lesion (LSIL), and 13% had high-grade squamous intraepithelial lesion (HSIL). There were no cancers. Abnormal cytology and high-risk HPV positivity were strongly correlated with low CD4 counts and high HIV viral loads. The most prevalent types of HPV were HPV-16, -52, -53, -35, and -18. Incident high-risk HPV infection occurred in 22%, and of those infected with high-risk HPV, 94% of infections persisted over an 18-month period, and 6% cleared their infections. Cytologic progression to SIL from normal/atypical squamous cells of undetermined significance cytology occurred in 17% of cases, but only 4% of cases of LSIL progressed to HSIL. CONCLUSION: There is a high level of high-risk HPV infection in HIV-1 infected women, but progression to HSIL over 36 months occurred in the minority of cases. We recommend an initial colposcopy for an abnormal test, and if no high-grade lesion is identified, triennial screening would be appropriate. Human papillomavirus type 16 was the commonest, and HPV-18 was the fifth commonest, suggesting that vaccination against these two types would have a significant effect. LEVEL OF EVIDENCE: II.     

Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening

Human papillomavirus (HPV) DNA testing was recently approved by the Food and Drug Administration for use as an adjunct to cytology for cervical cancer screening. To help provide guidance to clinicians and patients when using HPV DNA testing as an adjunct to cervical cytology for screening, a workshop was cosponsored by the National Institutes of Health-National Cancer Institute, American Society of Colposcopy and Cervical Pathology (ASCCP), and American Cancer Society. Consensus was reached based on a literature review, expert opinion, and unpublished results from large ongoing screening studies. The conclusions of the workshop were that HPV DNA testing may be added to cervical cytology for screening in women aged 30 years or more. Women whose results are negative by both HPV DNA testing and cytology should not be rescreened before 3 years. Women whose results are negative by cytology, but are high-risk HPV DNA positive, are at a relatively low risk of having high-grade cervical neoplasia, and colposcopy should not be performed routinely in this setting. Instead, HPV DNA testing along with cervical cytology should be repeated in these women at 6 to 12 months. If test results of either are abnormal, colposcopy should then be performed. This guidance should assist clinicians in utilizing HPV DNA testing in an effective manner, while minimizing unnecessary evaluations and treatments.     

Telomerase activity in Papanicolaou smear-negative exfoliated cervical cells and its association with lesions and oncogenic human papillomaviruses

OBJECTIVE: The goal of this study was to evaluate telomerase activity in exfoliated cervical cells and its association with cytology, pathology, and human papillomavirus (HPV). METHODS: Telomerase activity and HPV DNA sequences were examined in the exfoliated cervical cells from a general population of 245 women aged more than 30 years undergoing routine cervical screening by Papanicolaou smear. The women who were found to have telomerase activity or abnormal cytology in their exfoliated cervical cells were examined for cervical lesions by colposcopy and biopsy. RESULTS: Cytology for our population (mean, 56 years) revealed only one abnormal smear (1/245, 0.4%), in which a cervical intraepithelial neoplasia grade I (CIN I) lesion was found. The exfoliated cervical cells used to prepare the smear were negative for telomerase and contained low-risk HPV DNA. Telomerase activity was found in 16 exfoliated cell samples (16/245, 6.5%); high-risk HPV DNA was found in 9 of these samples (9/16, 56%) and 9 of the biopsy specimens that could be evaluated from patients testing positive for telomerase revealed CIN I lesions (9/11, 82%). CONCLUSIONS: Telomerase activity is often associated with high-risk HPV infection and it is suggested that telomerase assay can help to detect occult cervical lesions.     

Human papillomavirus type 16 and 18 detection in the management of mild dyskaryosis

Objective To determine if semi-quantitative human papillomavirus (HPV) types 16 and 18 detection by polymerase chain reaction can increase the sensitivity and specificity of repeat cytology alone for underlying high grade cervical intraepithelial neoplasia (CIN).
Design Prospective randomised study of immediate treatment and surveillance.
Setting A dedicated colposcopy clinic serving a regional population.
Sample Three hundred and four women with smears reported as mild dyskaryosis.
Methods Repeat cytology, HPV 16 and 18 tests, and colposcopy were performed at study entry. Women were randomised to either immediate treatment or surveillance with repeated tests at 6 and 12 months. Unless all study smears were negative, women were treated at study exit by large loop excision of the transformation zone.
Main outcome measures Sensitivity and specificity of HPV testing for types 16 and 18 in conjunction with cytology for high grade CIN.
Results Combining repeat cytology with HPV 16 and 18 testing had a sensitivity of 94% and a specificity of 26%., a positive predictive value of 71%, and a negative predictive value of 71%, for underlying high grade CIN. If used to secondary screen in conjunction with repeat cytology for mild dyskaryosis, 88% of women would have been referred for colposcopy on the basis of either test being positive.
Conclusion Combining repeat cytology and HPV 16 and 18 detection would result in the majority of women being referred for immediate colposcopy. Taken with an overall default rate of 17%, immediate referral of all women with mild dyskaryosis for colposcopic assessment still appears to be a more effective clinical strategy.     

Different Detectability of High-Risk HPV in Smears from Incident and Prevalent High-Grade Squamous Intraepithelial Lesions of the Cervix

Human papillomavirus (HPV) status in cervical smears from cervical intraepithelial neoplasia (CIN) 2/3 diagnosed in 36 of 892 women with a history of normal cytology and colposcopy (incident CIN 2/3) was compared with CIN 2/3 in 40 patients with a history of abnormal cytology (prevalent CIN 2/3). In all patients cervical smears for HPV testing and cytology and two cervigrams were taken. The scrapes were collected in hybrid capture assay solution and analyzed with the hybrid capture and general primer/type-specific primer polymerase chain reaction system (GP/TS-PCR) after DNA extraction. Patients with incident and prevalent CIN 2/3 were similar with respect to age. By GP/TS-PCR carried out under suboptimal conditions due to DNA extraction, HPV DNA was detected in 69.4% (25 of 36) of smears from incident CIN 2/3 compared to 95% (38 of 40) in prevalent CIN 2/3 (P= 0.003). Using hybrid capture, smears of incident CIN 2/3 were HPV positive in 50% (18 of 36) compared to 80% (32 of 40) in prevalent CIN 2/3 (P= 0.006). High-risk HPVs were significantly less common in smears from incident CIN 2/3 compared with prevalent CIN 2/3: 36.1% vs 72.5% by GP/TS-PCR (P= 0.001) and 47.2% vs 80% by hybrid capture assay (P= 0.003), respectively. Virus load in HPV-positive smears of prevalent CIN 2/3 was significantly higher than of incident CIN 2/3 using semiquantitative PCR (P= 0.0005). Thus, high-risk HPV types were detected less frequently and in lower concentration in smears from incident CIN 2/3 than in smears from prevalent CIN 2/3.     

Human papillomavirus type 16 and 18 detection in the management of mild dyskaryosis.

OBJECTIVE: To determine if semi-quantitative human papillomavirus (HPV) types 16 and 18 detection by polymerase chain reaction can increase the sensitivity and specificity of repeat cytology alone for underlying high grade cervical intraepithelial neoplasia (CIN). DESIGN: Prospective randomised study of immediate treatment and surveillance. SETTING: A dedicated colposcopy clinic serving a regional population. SAMPLE: Three hundred and four women with smears reported as mild dyskaryosis. METHODS: Repeat cytology, HPV 16 and 18 tests, and colposcopy were performed at study entry. Women were randomised to either immediate treatment or surveillance with repeated tests at 6 and 12 months. Unless all study smears were negative, women were treated at study exit by large loop excision of the transformation zone. MAIN OUTCOME MEASURES: Sensitivity and specificity of HPV testing for types 16 and 18 in conjunction with cytology for high grade CIN. RESULTS: Combining repeat cytology with HPV 16 and 18 testing had a sensitivity of 94% and a specificity of 26%, a positive predictive value of 71%, and a negative predictive value of 71%, for underlying high grade CIN. If used to secondary screen in conjunction with repeat cytology for mild dyskaryosis, 88% of women would have been referred for colposcopy on the basis of either test being positive. CONCLUSION: Combining repeat cytology and HPV 16 and 18 detection would result in the majority of women being referred for immediate colposcopy. Taken with an overall default rate of 17%, immediate referral of all women with mild dyskaryosis for colposcopic assessment still appears to be a more effective clinical strategy.     

Evaluation of HPV 16 PCR detection in self- compared with clinician-collected samples in women referred for colposcopy

OBJECTIVES: A clinical prospective evaluation study was conducted to evaluate PCR detection of high-risk human papillomavirus (HPV) type 16 in self-sampled vaginal compared with clinician-collected cervical specimens. METHODS: Paired vaginal and cervical specimens were collected from 137 consecutive women referred for colposcopy because of abnormal cervical cytology. In-house and a commercial PCR method for HPV type 16 were used. Self-sampled vaginal HPV 16 detection was compared to histology and physician-collected cervical specimens. RESULTS: Of the 137 patients, 98 had proven abnormal histology and were included in the analysis. Overall, using the cervix HPV detection as reference method, the self-sampled vaginal sample showed sensitivity 91.8%, specificity 96.1% and agreement kappa (kappa) 0.881. Using the histology as reference, all 11 cervical cancer cases were HPV-16-positive in both cervical and vaginal samples, and in 43 high-grade lesions, detection sensitivity in cervix was 72.1% (kappa 0.588) and vagina 67.4% (kappa 0.516). HPV 16 detection did not differ (P=0.27) between clinician-collected cervical and self-sampled vaginal specimens. CONCLUSIONS: The self-collected vaginal sample is highly concordant with the physician-collected cervical sample in HPV 16 detection.     

Precancerous lesions and cervical cancer vs HPV infection in pregnant women--cytological assessment

An effort has been made in order to estimate the relationship between HPV, cervical intraepithelial neoplasia and cervical carcinoma. The authors have been trying also to create a reliable prophylactic scheme as far as precancerous lesions and cervical carcinoma are concerned. 2243 pregnant women have been subjected to cytology and colposcopy examination. In selected cases HPV DNA hybridisation technique examination of cervical smear as well as colposcopy directed punch biopsy have been performed. The results of the study indicate of high efficiency of these methods in cervical cancer prophylaxis.     

Human papillomavirus testing for primary screening in women at low risk of developing cervical cancer. The Greek experience

OBJECTIVE: To compare the performance of human papillomavirus (HPV) DNA detection against routine Papanicolaou smear for the detection of low- and high-grade cervical intraepithelial neoplasia in a low-risk population. MATERIALS AND METHODS: A cross-sectional study was performed involving 1296 women attending six outpatient clinics in Northern Greece (Thessaloniki, Thermi, Mihaniona, Corfu, Veria, and Serres). Women underwent a gynecological examination, including collection of exfoliated cervical cells for Papanicolaou cytology and HPV DNA detection. Cytology was processed according the conventional routine manner, and HPV DNA was determined using the polymerase chain reaction technique. In positive cases of either method, a complete colposcopic evaluation was performed with directed biopsies. Tests (HPV DNA, cytology, and colposcopy) performance characteristics were determined using the histopathologic diagnosis as the reference standard. RESULTS: HPV DNA testing showed a significantly better sensitivity than the Papanicolaou smear in detecting cervical intraepithelial neoplasia (75% versus 50% for high-grade lesions and 81.2% versus 50% for lesions of any grade, respectively). Specificity, and positive and negative predictive values did not significantly differ. Even after dividing women in younger or older than 30 years, the sensitivity of the HPV DNA test was greater than cytology (100% and 70% versus 50% for cytology in both groups, respectively), with a 6.3% loss in specificity when performed in women younger than 30 years. CONCLUSION: HPV testing could be useful in screening women at low risk for cervical cancer, either as an adjunct tool to augment existing cytology programs or as a unique test of its own.