High-grade Squamous Intraepithelial Lesions In Women Research Articles

ДЕТЕКЦІЯ МАРКЕРІВ Р16/KI-67ПРИ ВИЯВЛЕННІ ІНТРАЕПІТЕЛІАЛЬНОЇ НЕОПЛАЗІЇ ШИЙКИ МАТКИ

B a c k g r o u n d . In recent years, Ukraine has experienced an unfavorable epidemiological situation concerning sexually transmitted diseases. One rapidly spreading infection is genital human papillomavirus (HPV). Convincing research has identified human papillomavirus (HPV) as a significant factor in the development of malignant transformations in the cervix. The study of the molecular pathogenesis associated with HPV-related neoplasms has led to the discovery of biomarkers aiding in the diagnosis of High-grade Squamous Intraepithelial Lesion (HSIL) of the cervix. Including the biomarkers p16/Ki-67 in the investigation enhances sensitivity in detecting HSIL in women. Additionally, it is pertinent to further analyze the effectiveness of using an additional semi-quantitative scale to assess the results of immunocytochemical detection of p16/Ki-67. M e t h o d s . The research was conducted on biological material from cervical smears using liquid-based cytology. Techniques included Papanicolaou staining, HPV detection, and immunocytochemical staining against p16/Ki-67. The sample comprised 90 women divided into three age groups, each categorized based on criteria such as HPV presence/absence, Bethesda classification of dysplasia, and negative/positive p16/Ki-67 results. Intensity of staining was further scored on a scale in the corresponding location of positive reactions in the nucleus or cytoplasm. R e s u l t s . The study revealed that immunocytochemical markers p16 and Ki-67 identified women with intraepithelial lesions, especially in cases with positive HPV results and no dysplastic changes in the Pap test. The intensity of immunocytochemical staining for p16 and Ki-67 varied directly with the detected degree of dysplasia. C o n c l u s i o n s . A direct correlation was observed between the severity of dysplasia established by Bethesda classification and the intensity of immunocytochemical staining for p16 and Ki-67. These findings provide an opportunity for further exploration of staining intensity in the presence of immunocytochemical markers p16 and Ki-67 for their potential use in the comprehensive interpretation of Pap test results and the precise identification of dysplasia in ambiguous diagnostic samples.

Impact of a High-Resolution Anoscopy Clinic on Management of Anal Dysplasia in Women Living With HIV.

The rate of anal squamous cell cancer (aSCC) is increasing among women living with HIV. Treatment of precursor high grade squamous intraepithelial lesions (HSIL) may reduce the risk of progression to aSCC. The objective of this study was to examine effects of a dedicated high-resolution anoscopy (HRA) clinic on management of HSIL in women with HIV. Women living with HIV who underwent anal dysplasia screening at a single institution between 2006 and 2020 were reviewed. Those who underwent screening before (Group A) and after (Group B) the implementation of an HRA program in 2017 were compared. The primary outcome of interest was the successful detection and treatment of HSIL. A total of 201 women living with HIV underwent anal dysplasia screening between 2006 and 2020. Seventy-seven patients were found to have abnormal anal cytology requiring further treatment: 43 (55.8%) in Group A and 34 (44.2%) patients in Group B. Of the patients with abnormal anal cytology, 76.7% of patients in Group A received further biopsy and treatment, whereas 79.4% of Group B patients underwent subsequent biopsy and treatment. In propensity score weighting logistic regression analysis, the Group B was 4.6 times as likely to diagnosis HSIL on biopsy compared to Group A (OR = 4.60, 95% CI: 1.15 to 18.38, P = .03). Anal dysplasia is common among women living with HIV. The establishment of a HRA program was associated with increased identification and treatment of HSIL among women living with HIV, which may prevent the progression to aSCC.

Screening for intra-anal squamous intra-epithelial lesions in women with a history of human papillomavirus-related vulvar or perianal disease: results of a screening protocol.

Women with a history of human papillomavirus (HPV)-related cervical, vaginal or vulvar high-grade squamous intra-epithelial lesions (HSILs) or cancer are at increased risk of developing anal squamous intra-epithelial lesions (SILs) or a squamous cell carcinoma of the anus (SCCA). Screening for intra-anal SILs with high-resolution anoscopy (HRA) in high-risk populations is a subject of debate. In this study we aimed to answer the following question: what is the prevalence of intra-anal (H)SIL in women with HPV-related vulvar and/or perianal disease using HRA for screening? A retrospective study was performed to evaluate the prevalence of intra-anal (H)SIL in women with a history of vulvar and/or perianal HSIL or (superficially invasive) squamous cell carcinoma (SCC). This study was performed between 2015 and 2018 following implementation of a protocol for intra-anal screening using HRA. Twenty-seven patients, 10 with a history of (superficially invasive) SCC (four vulvar, five perianal, one multizonal) and 17 with HSIL as the worst diagnosis (two perianal, 15 multizonal) were screened for intra-anal lesions using HRA. No anal cancer was found at screening, 6 (22%) patients were diagnosed with intra-anal HSIL and 12 (44%) patients with intra-anal low-grade SIL. We found a high prevalence of intra-anal HSIL in women previously diagnosed with vulvar and perianal HSIL. Given the clear link between HSIL and SCCA, screening for intra-anal lesions in women with HPV-related genital pathology seems warranted. Future studies should focus on the effect of HSIL treatment on the prevention of anal cancer.

Use of electrical impedance spectroscopy as an adjunct to colposcopy in a pathway of cervical intraepithelial neoplasia diagnostics.

Screening with cytology decreases cervical cancer burden, but new methods have emerged. We assessed thediagnostic value of electrical impedance spectroscopy (EIS) in the real-world gynecological setting. The study aimed todetermine the diagnostic usefulness of EIS used as an adjunct to colposcopies in the diagnosis of high-grade squamousintraepithelial lesions in women with abnormal cytology findings. A cross-sectional, single center, observational study considered 143 women. All were subjected toa colposcopy and EIS with ZedScan. ZedScan-guided or colposcopically-guided biopsies were carried out. Data from 118 women were analyzed. The average age of the included women was 38.29 } 12.52 years (range:22-86 years). Overall, 27 had a diagnosis of CIN2+ and above on histopathological examination, 99 had low-grade colposcopyresults, 18 had high-grade colposcopy results, and 80 had positive ZedScan examination. No adverse events relatedto the examination with ZedScan were observed. EIS used as an adjunct to colposcopies showed sensitivity of 96.30%(95% CI: 81.03-99.91) and specificity of 39.56% (95% CI: 29.46-50.36), and accuracy of 52.54% (95% CI: 43.15-61.81). Theprocedure allowed to detect 11 additional cases with positive histo-pathological result in comparison to colposcopies alone. Colposcopies performed with ZedScan as an adjunct were effective in detecting high-grade cervical lesions.Advantages of ZedScan include real-time result display, no additional diagnostic burden posed on the patient, andgood safety profile. Studies on large patient cohorts are needed for further evaluations of this diagnostic procedure andfactors which may affect its diagnostic accuracy.

Accuracy of colposcopy-directed biopsy in detecting early cervical neoplasia: a retrospective study.

Colposcopy-directed biopsy is a cornerstone method for diagnosing cervical intraepithelial neoplasia. The aim of this study was to evaluate the accuracy of colposcopy-directed biopsy in comparison with definitive surgery. The accuracy of colposcopy-directed biopsy was compared with the final histology in relation to different types of transformation zone (TZ), the patient's age, and the examiner's level of training. The overall accuracy of biopsy in comparison with definitive surgery was 71.9% for all entities-benign lesions, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions (HSILs), and cervical carcinoma-with an underdiagnosis rate of 11.8% and an overdiagnosis rate of 16.5%. The accuracy for detecting HSIL was 88% (401/455), with an underdiagnosis rate of 10.5% and overdiagnosis rate of 1.3%. The accuracy rates for detecting HSIL in women with TZ1, TZ2, or TZ3 were 92.2, 90.5, and 76.5%, respectively. The accuracy rates for detecting HSIL in the different age groups were 93.1% (age 0-34), 83.6% (age 34-55), and 80% (age 55 or older). A combination of the colposcopic findings, cytology, human papillomavirus testing, and colposcopy-directed biopsy is necessary for the correct diagnosis of HSIL. The accuracy rate depends on the TZ and the patient's age. The examiner's level of training does not have any substantial influence on the accuracy.

17 - Screening for anal dysplasia in women with a history of human papillomavirus related lower genital tract pathology

Background Women with a human papillomavirus related history of cervical, vaginal or vulvar high-grade dysplasia or cancer are at increased risk to develop anal dysplasia or anal cancer. Screening for anal cancer precursors (squamous intraepithelial lesions (SIL)) with high resolution anoscopy (HRA) in high-risk populations is subject of debate. In this study we evaluated standardized intra-anal SIL screening using HRA in high-risk female patients. Methods A retrospective observational study was performed to evaluate the prevalence of intra-anal SIL in women with a history of vulvar high-grade SIL (HSIL) and perianal HSIL diagnosed at the Netherlands Cancer Institute, who were referred for intra-anal SIL screening using HRA in the MC Slotervaart between 2015 and 2017. Results 22 female patients were screened for anal SIL using HRA. 19 females had a history of biopsy proven vulvar HSIL and 19 females had a history of biopsy proven perianal HSIL. Eleven (50%) patients had a history of multizonal HSIL at three or more perianogenital locations. No anal cancer was found at screening, 7 (32%) patients were diagnosed with anal HSIL and 7 (32%) patients with low-grade anal SIL. Conclusions We found a high prevalence of anal HSIL in women with HPV related lower genital tract dysplasia. Intra-anal SIL screening using HRA in this high risk population seems to be justified. However, HRA is an invasive screening method. Studying other, less invasive screening methods remains important.

Immunoexpression of HPV 16/18 E6 and E7 oncoproteins in high-grade cervical squamous intraepithelial lesions in HIV-positive women.

The aim of this study was to assess the immunoexpression of human papillomavirus genotypes 16 and 18 (E6 and E7) oncoproteins in cervical high-grade squamous intraepithelial lesions (HSIL) of human immunodeficiency virus (HIV)-positive women. These results were also compared to the persistence and/or recurrence of lesions after loop electrosurgical excision procedure. Cervical samples from 158 patients were divided into three groups according to the presence or absence of HSIL in women who were or were not HIV-positive. By using the tissue microarray technique, immunohistochemistry was performed to analyze the expression of HPV 16/18 E6 and E7 oncoproteins. Cervical samples from 95 HIV-positive women and 63 HIV-negative women were studied. A statistically significant difference was found in the immunoexpression of E6 and E7 oncoproteins in samples from HIV-positive women with HSIL and that of women with non-neoplastic tissue (P < 0.001). There was also a statistically significant correlation between the immunoexpression of E6 (P = 0.012) and E7 (P < 0.001) oncoproteins in lesion persistence among HIV-positive women. Within the limitations of this study, the immunoexpression of HPV 16/18 E6 and E7 oncoproteins may have prognostic value regarding lesion persistence in HIV-positive women.

P16 Immunohistochemistry is useful in confirming high-grade squamous intraepithelial lesions (HSIL) in women with negative HPV testing.

It is believed that almost all squamous cell carcinomas of the cervix are associated with HR-HPV infection. However, a subset of high-grade squamous intraepithelial lesion (HSIL) (CIN2 and CIN3) lesions is found in those women with negative HPV testing. Knowledge of HPV status can influence pathologists' decision in rendering the diagnosis of cervical squamous intraepithelial lesions (SIL). p16, a surrogate marker for HSIL, has been widely applied to facilitate accurate diagnosis of HPV-related cervical dysplasia, especially CIN2 and CIN3. To assess whether p16 immunostaining is useful in diagnosing HSIL in women with negative HPV testing, we studied the utility of p16 immunohistochemistry in 46 women of HSIL and HPV-negative status. A total of 46 cases of initial biopsies with histopathologically diagnosed HSIL (CIN2 and CIN3) were identified from our hospital archives. All women were HPV negative with at least 1 HPV testing using HC-II (Qiagen) within 6 mo of initial biopsy. LEEP procedures within 6 mo of initial biopsies were reviewed and documented. Immunohistochemical staining of p16 was performed on recuts of all original biopsies. Some LEEP specimens without evidence of HSIL (CIN2 and CIN3) on hematoxylin and eosin had recuts with deeper levels and p16 immunostaining to confirm the negative diagnosis. p16 immunostaining were evaluated as negative, focal/patchy, or diffuse staining pattern. Patients' HPV testing status and related clinicopathologic information were reviewed, tabulated, and correlated with p16 immunostaining patterns. Forty-six women between the age of 17 and 58 yr, with a median of 35 yr, were all HPV-negative. All women, except 2, had an abnormal cytologic interpretation at the time of HPV testing ranging from ASC-US to HSIL. Forty-two women (91.3%) had LEEP procedures done within 6 mo of the initial biopsies. LEEP specimens showed that 76.2% (32 cases) women had HSIL, including 22 cases of CIN2 and 10 cases of CIN3, 14.3% (6 cases) had low-grade squamous intraepithelial lesion (CIN1), and 9.5% (4 cases) had benign cervix. p16 immunostaining, performed on initial biopsies with histopathologic diagnoses of CIN2 or CIN3, showed that 66.7% (28 cases) had diffuse staining pattern, 16.7% (7 cases) had focal/patchy pattern, and 16.7% (7 cases) had negative p16 staining. On LEEP follow-up, all 28 cases with diffuse p16 staining pattern had HSIL (CIN2 and CIN3), and all 7 cases with negative p16 staining had no detectable high-grade dysplasia. For those 7 cases with focal/patch p16 staining pattern, 4 had HSIL (CIN2) and 3 had low-grade squamous intraepithelial lesion (CIN1) on LEEP follow-up. Approximately 76% of women with negative HPV and diagnosis of HSIL (CIN2 and CIN3) on initial biopsy had confirmed HSIL (CIN2 and CIN3) in subsequent LEEP follow-up. Diffuse p16 immunostaining pattern is the hallmark of HSIL because it correlates 100% with CIN2 and CIN3 lesions between initial biopsy and LEEP specimens, regardless of the HPV status. The negative predictive value for p16 immunoreactivity to predict cervical lesions less than high grade is almost 100% in our study. Our study suggests that when a woman is negative for HPV and also negative for p16, diagnosis of HSIL should be very cautious in void of unnecessary LEEP procedures.

No Evidence for Synergy Between Human Papillomavirus Genotypes for the Risk of High-Grade Squamous Intraepithelial Lesions in a Large Population-Based Study

Multiple human papillomavirus (HPV) genotypes may be independently or synergistically associated with risk of high-grade squamous intraepithelial lesions (HSILs). We evaluated the risk of HSIL in women concomitantly infected with multiple HPV genotypes. A population-based stratified sample of 59 664 cervical cytology specimens from women residing in New Mexico were evaluated for cytologic abnormalities and HPV genotypes. We calculated the risk of HSIL in women infected with a single HPV genotype and the risk in those infected with multiple HPV genotypes. The highest risk of HSIL was observed for HPV-16 (0.036), followed by HPV-33 (0.028), HPV-58 (0.024), and HPV-18 (0.022). For most types, we observed a greater risk of HSIL in women infected with multiple carcinogenic HPV types. In contrast, the risk of HSIL was similar in women infected with HPV-16 and other types, compared with women infected with HPV-16 only. We observed an increased but plateauing risk of HSIL in women infected with multiple types, compared with those infected with a single type, with risk ratios of 1.5 (95% confidence interval [CI], 1.2-1.8), 1.7 (95% CI, 1.3-2.4), and 1.4 (95% CI, 0.83-2.5) for women infected with 2, 3, and ≥4 genotypes, respectively. In the largest population-based study of HPV genotypes and cytologic outcomes so far, we did not see more than additive effects of HPV types on the risk of HSIL in women infected with multiple types.

Significance of HPV-58 Infection in Women Who Are HPV-Positive, Cytology-Negative and Living in a Country with a High Prevalence of HPV-58 Infection

PurposeCervical cytology and human papillomavirus (HPV) DNA co-testing is recommended as a screening method for detecting cervical lesions. However, for women who are HPV-positive but cytology-negative, the appropriate management and significance of HPV-58 infection remain unknown.MethodsThis study of prevalent HPV detected at baseline with a median follow-up of 3.2 years evaluated the risk factors associated with cervical abnormalities and assessed the significance of HPV-58 infection. A total of 265 women were enrolled. All high-grade squamous intraepithelial lesions (HSIL) that were detected by cytology were confirmed by histology. Histological diagnoses of cervical intraepithelial neoplasia 2/3 were classified as HSIL. Women were classified into four groups according to the HPV genotype that was detected at their first visit: HPV-58 (n = 27), HPV-16 (n = 52; 3 women had HPV-58 co-infection), ten other high risk (HR) types (n = 79), or low/undetermined risk types (n = 107).ResultsOf 265 women, 20 (7.5%) had HSIL on their follow-up examinations. There were significant differences in the cumulative incidence of HSIL between the four groups (p<0.001). The 5-year cumulative incidence rates of HSIL were 34.0% (95% CI: 17.3–59.8%) in HPV-58 positive cases, 28.0% (95% CI: 13.8–51.6) in HPV-16 positive cases, 5.5% (95% CI: 2.1–14.0%) in one of the ten other types of HR-HPV positive cases, and 0% in women with low/undetermined risk HPV. When seen in women with HR-HPV (n = 158), persistent HPV infection was a significant factor associated with the development of HSIL (hazard ratio = 15.459, 95% CI: 2.042–117.045). Women with HPV-58 had a higher risk (hazard ratio = 5.260, 95% CI: 1.538–17.987) for the development of HSIL than women with HPV-16 (hazard ratio = 3.822, 95% CI: 1.176–12.424) in comparison with women with other types of HR-HPV.ConclusionHPV-58 has a high association with the development of HSIL in women who are HPV-positive and cytology-negative.

The Role ofp73G4C14-to-A4T14 Polymorphism in the Susceptibility to Cervical Cancer

Several reports have suggested the importance of p73 polymorphisms in tumor behavior. We investigated the role of a p73 gene polymorphism in the susceptibility to cervical lesions in a southwestern European population. Peripheral blood samples were obtained from Radiotherapy and Gynaecology Departments of Portuguese Institute of Oncology (Porto, Portugal), from 1998 to 2002. We analyzed the p73 cytosine thymine polymorphism in peripheral blood DNA of 176 healthy donors, 38 high-grade squamous intraepithelial lesions (HSIL), and 141 patients with primary untreated invasive cervical cancers (ICC), by polymerase chain reaction-restriction fragment length polymorphism. Our results demonstrate a twofold increased susceptibility to the development of HSIL in women carrying the p73 AT allele (OR=2.39; p=0.022). Further, this association seems to be more evident in women with high parity (OR=12.53; p=0.007). This is in agreement with the possible role of p73 in cervical carcinogenesis, namely, in human papillomavirus-infected transition zone subjected to the action of estrogens and in conjunction with disruption of differentiation program of this squamous epithelium that occurs in HSIL phase before the next step to invasiveness and squamous cervical cancer.

Utilidad de la detección del virus del papiloma humano de alto riesgo mediante Hybrid Capture II ® en mujeres con citologías anormales del cuello uterino

The objectives of the study were to investigate the usefulness of high-risk human papillomavirus (HR-HPV) detection in women with abnormal pap-smears as an adjunct to screening by cervical cytology, and to determine the viral load distribution according to the histological grade of the lesions. A total of 75 women were referred for cytological study of atypical cells of unknown origin (ASCUS), low-grade squamous intraepithelial lesions (LG-SIL) or high-grade squamous intraepithelial lesions (HG-SIL). All patients underwent colposcopy, histological study and HR-HPV detection using the Hybrid Capture II test. In the pap-smear studies, HR-HPV was detected in 31.2% of women with ASCUS and 65.7% with LG-SIL. Histological examination showed HR-HPV in 46.4% of women without lesions, 69.5% of those with LG-SIL and 75% with HG-SIL. Negative predictive values for HG-SIL in women with cytological diagnoses of ASCUS and LG-SIL were 81.8% and 92.3%, respectively. Percentages of infection with high viral load significantly increased in accordance with the histological grade. The Hybrid Capture II test can be useful for the management of women with cytological evidence of ASCUS because of the low prevalence of HR-HPV infection and the high negative predictive value for HG-SIL. The usefulness in women with a cytological diagnosis of LG-SIL is limited due to the high prevalence of HR-HPV infection. High viral load can be a risk factor for the development of premalignant cervical lesions.

Association of Tumor Necrosis Factora-2anda-8Microsatellite Alleles with Human Papillomavirus and Squamous Intraepithelial Lesions among Women in Brazil

Infection with oncogenic human papillomavirus (HPV) is considered to be the major risk factor for cervical cancer. Tumor necrosis factor (TNF) is a pluripotent cytokine that plays an important role in inhibiting the action of microbial agents, and TNF microsatellite polymorphisms have been associated with several diseases, including cancer and viral infections. This study analyzed the associations between TNFa to -e microsatellite polymorphisms and the severity of squamous intraepithelial lesions (SIL), according to the presence of the oncogenic HPV16 and HPV18 types. Samples from 146 HPV-positive women with low-grade SIL (LSIL) and high-grade SIL (HSIL) and samples from 101 healthy women were studied. TNF microsatellite polymorphism typing and HPV detection and typing were performed using PCR-amplified DNA hybridized with sequence-specific primers. Data were analyzed by Fisher's exact test using the GENEPOP software. Significant associations were observed between LSIL and the TNFa-8 allele (4/166; P = 0.04), as well as between TNFa-2 with HPV18 only (16/44; P = 0.002) and TNFa-2 with HPV18 coinfection with HPV16 (16/44; P = 0.001). Patients exhibiting the TNFa-2 allele and harboring HPV18, in the presence or absence of coinfection with HPV16, had an increased risk of HSIL occurrence (13/38; P = 0.04; 5/10; P = 0.04) compared to patients with other HPV types. These results suggest that the TNFa-8 allele is associated with increased susceptibility to the occurrence of LSIL and that despite the presence of a high TNF-alpha production allele, the ability of HPV18 to resist the inhibitory effects of TNF-alpha may contribute to the occurrence of infection and consequently to HSIL in women with cervical HPV18 infection.

Managing Atypical Squamous Cells of Undetermined Significance (ASCUS): Human Papillomavirus Testing, ASCUS Subtyping, or Follow-Up Cytology?

Colposcopically directed biopsy finds high-grade squamous intraepithelial lesion (HSIL) in the histologic specimen of 5% to 15% of cervical smears taken from women with a diagnosis of atypical squamous cells of undetermined significance (ASCUS). This study was designed to investigate the ability of human papillomavirus (HPV) testing, ASCUS subtyping, and follow-up cytology to predict the presence of HSIL in the cervical smear. The study material consisted of 918 liquid-based cervical cytologic samples (ThinPrep test, Cytec Corp, Boxborough, MA) collected in a single pathologic laboratory between 1997 and 2000. HPV testing was carried out in 704 of the samples that had sufficient cytologic material remaining for follow-up cytologic examination, including 105 with a normal diagnosis, 426 cases of ASCUS, 126 with low-grade squamous intraepithelial lesion (LSIL), and 47 with HSIL. The cervical samples of 91% of the women with HSIL, 88% of those with LSIL, and 49% of those with ASCUS were positive for all HPV types, but only 27% of those with normal cervical cytology contained all HPV types. When only high-risk HPV types were considered, the percentage of positivity for normal samples dropped to 19% and the percentage for HSIL increased to 96%. The ASCUS category was further sorted into ASCUS, favor reactive (AFR); ASCUS, not otherwise specified (ANOS); ASCUS, favor LSIL (AFLS); and ASCUS, favor HSIL (AFHS). Both high- and low-risk HPV types were found in AFR and ANOS samples slightly more frequently than in normal samples. High- and low-risk HPV types were found in AFLS far more frequently than in normal smears but slightly less than for LSIL. This pattern continued with the progression from LSIL to AFHS and from AFHS to HSIL. Three hundred eighty-six women of the 704 women had a year or more of follow-up data available, including a biopsy or other tests within 1 year of the cervical smear. Eight women with an initial diagnosis of ASCUS progressed to HSIL (3.4%). The presence of HPV was detected in the samples of all of these women, including high-risk HPV in seven of the eight, yielding a sensitivity of 88% and a specificity of 73% for high-risk HPV testing in predicting the development of HSIL in women with ASCUS. The positive predictive value for high-risk HPV testing was 11%. The sensitivity of any type HPV testing was 100%, but the specificity was only 48%. In all, 64% of the women for whom follow-up data were available regressed to normal. Compared with the 3.4% of ASCUS women who were found to have HSIL, 11% of the positive high-risk HPV patients developed HSIL. A designation of AFHS led to HSIL in 25% of the women with an initial diagnosis of ASCUS. Only 1.1% of the ASCUS women designated AFR later developed HSIL.

Identifying Women With Cervical Neoplasia

ContextA Papanicolaou (Pap) test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5% to 10% of women with ASCUS harbor serious cervical disease, but more than one third of the high-grade squamous intraepithelial lesions (HSILs) in screening populations are identified from ASCUS Pap test results.ObjectiveTo determine whether human papillomavirus (HPV) DNA testing of residual material from liquid-based Pap tests and referral of cases found to be HPV-positive directly to colposcopy could provide sensitive detection of underlying HSILs in women with ASCUS Pap results, compared with repeat Pap testing.Design and SettingNatural history of women with ASCUS Pap smear results, all of whom had liquid-based cytology, HPV testing, and subsequent repeat Pap tests and colposcopy with histologic evaluation, conducted at 12 gynecology clinics in a large managed care organization between October 1995 and June 1996.ParticipantsFrom a cohort of 46,009 women who had routine cervical examinations, 995 women with Pap test results of ASCUS who consented to participate were identified.Main Outcome MeasuresCervical histology, HPV test results, and repeat Pap smear results, and sensitivity of HPV testing to identify patients found to have HSIL+ histology.ResultsOf 995 participants with ASCUS Pap test results, 973 had both a definitive histologic diagnosis and HPV result. Sixty-five (6.7%) had histologic HSIL or cancer. For women with histologic HSIL+, the HPV test was positive in 89.2% (95% confidence interval [CI], 78.4%-95.2%), and the specificity was 64.1% (95% CI, 60.9%-67.2%). The repeat Pap smear result was abnormal in 76.2% (95% CI, 63.5%-85.7%). Triage based on HPV testing only or on repeat Pap testing only would refer similar proportions (approximately 39%) to colposcopy. The sensitivity of HPV DNA testing for HSIL was equivalent to, if not greater than, that of the repeat Pap test. We further estimated that an HPV-based algorithm including the immediate colposcopy of HPV-positive women, and then repeat Pap testing of all others, would provide an overall sensitivity of 96.9% (95% CI, 88.3%-99.5%).ConclusionsFor women with ASCUS Pap tests, HPV DNA testing of residual specimens collected for routine cervical cytology can help identify those who have underlying HSIL. By testing the specimen collected at initial screening, the majority of high-risk cases can be identified and referred for colposcopy based on a single screening.