Pap Diagnosis Research Articles

Analysis of the sensitivity of high-grade squamous intraepithelial lesion Pap diagnosis and interobserver variability with the Hologic Genius Digital Diagnostics System.

Artificial intelligence (AI)-based systems are transforming cytopathology practice. The aim of this study was to evaluate the sensitivity of high-grade squamous intraepithelial lesion (HSIL) Papanicolaou (Pap) diagnosis assisted by the Hologic Genius Digital Diagnostics System (GDDS). A validation study was performed with 890 ThinPrep Pap tests with the GDDS independently. From this set, a subset of 183 cases originally interpreted as HSIL confirmed histologically were included in this study. The sensitivity for detecting HSIL by three cytopathologists was calculated. Most HSIL cases were classified as atypical glandular cell/atypical squamous cell-high grade not excluded (AGC/ASC-H) and above by all cytopathologists. Of these cases, 11.5% were classified as low-grade squamous intraepithelial lesion (LSIL) by pathologist A (P-A), 6% by pathologist B (P-B), and 5.5% by pathologist C (P-C); 3.8%, 2.7%, and 1.6% of these cases were classified as atypical squamous cell of unknown significance (ASC-US) by P-A, P-B, and P-C, respectively. The sensitivity for detection of cervical intraepithelial neoplasia 2 and above (CIN2+) lesions was 100% if ASC-US and above (ASC-US+) abnormalities were counted among all three pathologists. The sensitivity for detection of CIN2+ lesions was 84.7%, 91.3%, and 92.9% by P-A, P-B, and P-C, respectively, for ASC-H and above abnormalities. The Kendall W coefficient was 0.722, which indicated strong agreement between all pathologists. New-generation AI-assisted Pap test screening systems such as the GDDS have the potential to transform cytology practice. In this study, the GDDS aided in interpreting HSIL in ThinPrep Pap tests, with good sensitivity and agreement between the pathologists who interacted with this system.

The Impact of an Educational Program on Cervical Cancer Knowledge Among HIV-Positive Women in Bali, Indonesia.

The burden of Human papillomavirus (HPV)-related cancers is expected to rise in Indonesia as there has been an increase in the availability of medication that prolongs the survival of women infected with the human immunodeficiency virus (HIV+). There is an urgent need for cervical cancer (CC) screening to address this concern. The objectives of the current study were to determine the burden of HPV infections and cervical pre-cancer lesions and evaluate the effectiveness of an education program to improve HPV and CC knowledge among women attending HIV clinics in Bali, Indonesia. A questionnaire focused on HPV and CC was administered to 200 HIV+ women before (pre-education) and after the education program (post-education). Cervical cells were used to perform the Papanicolaou (Pap) and test for 13high-risk (HR) HPV genotypes. Women diagnosed with Pap diagnoses of greater than atypical squamous cells of undetermined significance (≥ASCUS+) were identified as abnormal Pap. Fifty-four percent of women were diagnosed with ASCUS+ and 81% of those women were positive for any one of the 13HR-HPV genotypes while 71% were positive for any HPV genotype included in the 9-valent (9V) HPV vaccine. The percentages of women who answered questions correctly at the pre-education interview was 3-25% while 97-100% gave the correct answers to the same questions at the post-education interview (P<0.0001). Our study for the first-time documented that a significant proportion of women who attend HIV clinics in Bali are diagnosed with ASCUS+ and HR-HPVs which put them at high risk for developing CC. It would have been possible to prevent the development of ASCUS+ in at least 70% of those women if 9V HPV vaccine was given to these women. Since all 200 women educated by our program consented for screening, we clearly demonstrated that HIV+ women attending HIV clinics can be successfully educated to participate in CC screening.

Analysis of Sensitivity of High Grade Squamous Intraepithelial Lesion (HSIL) Pap diagnosis and Interobserver Variability with Hologic Genius Digital Diagnostics

Analysis of Sensitivity of High Grade Squamous Intraepithelial Lesion (HSIL) Pap diagnosis and Interobserver Variability with Hologic Genius Digital Diagnostics

Rates of CIN2 and CIN3+ in Women with Cervical Histology Following Pap Diagnoses of ASC-H vs. LGH: A 12-year Single Institution Experience

Rates of CIN2 and CIN3+ in Women with Cervical Histology Following Pap Diagnoses of ASC-H vs. LGH: A 12-year Single Institution Experience

Prevalence of Unsatisfactory Pap Smear and Associated Clinical History and Diagnosis in a Tertiary Teaching Hospital in Ghana

Background: A major limitation of cervical cytology is the unsuitability of proportion of smears submitted for analysis and for cytological assessment (unsatisfactory). This study examines the prevalence of unsatisfactory Pap smear, clinical history and diagnosis in the Department of Pathology, Korle-Bu Teaching Hospital (KBTH), Ghana. Materials and Methods: A retrospective review of 15,290 cases spanning 12 years (2005-2016) was carried out at the cytology unit of the Pathology Department of the KBTH. Out of the 15,290 Pap smear records retrieved, 2347 reports were excluded leaving 12,943 for the study. All unsatisfactory smear cases were analyzed and categorized using the Bethesda 2001 System. Results are presented using descriptive statistics. Results: The overall prevalence of unsatisfactory Pap smear was 402 (3.1%). Routine screening smear accounted for 115 (0.9%); reports without clinical history and diagnosis gave 21 (0.2%) and cases with clinical history and diagnosis were 287 (2.2%). The common cause of unsatisfactory Pap smear was scanty cellularity 222 (1.72%). Patient’s history accounted for the least cause of unsatisfactory Pap smear 2 (0.02%). Conclusion: Pap smear results reported as unsatisfactory could harbor cancer malignancy. Samples should be taken by well-trained persons.

Challenges in the Pap diagnosis of endocervical adenocarcinoma in situ

Recognition of adenocarcinoma in situ (AIS) in cervical cytology is challenging. We calculated the sensitivity and accuracy of Papanicolaou (Pap) tests obtained within 1 year of a histologic diagnosis of AIS from 2007 to 2016. We also correlated it with the coexistence of squamous lesions, calculated the interobserver agreement, and compared these measures with those of endocervical adenocarcinoma (ECCA). We correlated AIS detection with high-risk human papillomavirus (hrHPV) status. Of 72 patients with histologic AIS and 48 patients with ECCA, 92% and 87.5%, respectively, had abnormal Pap test results. A glandular abnormality was detected in 44.4% of the AIS and 77.1% of the ECCA cases. Complete cytohistologic concordance was reached in 8.3% of AIS and 22.9% of ECCA cases. In addition, 27.8% of AIS and 6.3% of ECCA cases were diagnosed on Pap as a high-risk squamous abnormality. Concurrent squamous lesions were present in 79.2% of patients with AIS and 29.2% of patients with ECCA. The Paps from the AIS and ECCA cases were diagnosed as pure squamous abnormalities in 47.2% and 10.4% of cases, respectively. In the AIS cases, interobserver agreement was substantial for detection of any high-risk cytologic abnormality (kappa = 0.67) and fair for detection of any glandular abnormality (kappa = 0.34). Among the 26 patients with AIS tested for hrHPV, 92% had positive results and 8% had negative results. The cytologic sensitivity for the detection of AIS remains low. It is directly related to the coexistence of squamous lesions. Cytology and hrHPV as stand-alone screening tests fail in the early detection of a small proportion of glandular lesions, although combined testing will improve their detection rates.

Retrospective Review of Unsatisfactory Gynecologic Pap Diagnosis and its Correlation with hrHPV Test Result

Retrospective Review of Unsatisfactory Gynecologic Pap Diagnosis and its Correlation with hrHPV Test Result

Abstract 433: Utility of p16 immunohistochemistry in evaluating negative cervical biopsies following high-risk pap test results

Abstract The Lower Anogenital Squamous Terminology (LAST) Standardization Project for HPV-associated Lesions recommends the use of p16 immunohistochemistry as an adjunct to morphologic assessment of cervical biopsies interpreted as negative from patients that are at high risk for missed high-grade disease (defined as a prior cytologic interpretation of HSIL, ASC-H, ASC-US/HPV-16+, or AGC-NOS) (Darragh et al., 2012). However, few studies have specifically evaluated the utility of performing p16 on negative cervical biopsies and endocervical curettage specimens following high-risk Pap test results. A search of the Stanford Cytopathology database from 7/1/2002-6/30/2012 for cervical cytology cases with diagnoses of ASC-H, HSIL, AGC-NOS, and atypical endocervical cells NOS (AGC-EC) yielded 1517 cases. Of these, 703 cases had histologic follow-up. Biopsies were excluded if diagnosed as atypical, low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL), or insufficient, or if the time to follow up was greater than 1 year. Immunostain for p16 (CINtec) was performed on 350 cases from 339 patients (age 16-85 yrs, average 42+/-14) and scored as positive (diffuse strong), negative or equivocal. 6 cases were excluded due to insufficient tissue and 3 cases with equivocal staining were excluded from further analysis. For p16(+) and equivocal cases, HPV in situ hybridization (ISH) (Ventana HPV III Family 16 probe) was performed and the corresponding H&amp;E section reviewed. Based on the H&amp;E review, the diagnosis was revised. Follow-up data was also obtained. 12/341 cases (3.5%) were p16(+) corresponding to missed diagnoses of LSIL (1 cases), HSIL-CIN2 (2 cases), and SIL-indeterminate grade (6 cases). Two biopsies from one patient at different time points exhibited p16 staining of bland metaplastic cells undermining endocervical glands that morphologically did not meet criteria for SIL and were interpreted as atypical metaplasia. Follow-up biopsies showed HSIL. p16 immunostain increases the detection rate of SIL by 3.5% in benign appearing cervical biopsies and endocervical curettages from patients with a prior high-risk Pap test result. The benefit of p16 immunostain is highest for cases with a prior Pap diagnosis of HSIL. Cytoplasmic only staining and staining of surface mucosa, endocervical glands, and tubal metaplasia may lead to over-interpretation of p16 as positive. Reference: Darragh, T. M. et al. The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Arch. Pathol. Lab. Med. 136, 1266-1297 (2012). Citation Format: Alana F. Shain, Shirley Kwok, Ann K. Folkins, Christina S. Kong. Utility of p16 immunohistochemistry in evaluating negative cervical biopsies following high-risk pap test results. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 433.

Cervical polyps: Is histologic evaluation necessary?

ObjectiveThe aim of this study was to examine a series of clinically identified cervical polyps and determine the incidence of significant histologic and concurrent cytologic findings. MethodsConsecutive cervical polyps from January 2000 through September 2012 were retrieved from the hospital laboratory information system. Histologic evaluation of these polyps was performed, followed by a chart review of clinical findings and correlation with the immediately prior or concurrently collected cervical Papanicolaou (Pap) test results, when available. ResultsA total of 369 cervical polyps were identified and reviewed. The patient ages ranged from 18 to 87 years (mean 46.5years). Eight polyps demonstrated squamous dysplasia (6 Cervical Intraepithelial Neoplasia/CIN I, and 2 CIN II/III), while 6 had malignant or atypical/potentially malignant features (2 adenosarcoma, 2 atypical polyps concerning for Mullerian adenosarcoma, 1 endometrioid endometrial adenocarcinoma and 1 adenocarcinoma in-situ). An increased incidence of atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells not otherwise specified (AGC NOS) Pap diagnoses (12.7% and 6.1%, respectively) was found in women with benign polyps on biopsy. DiscussionWe demonstrated a higher rate of clinically significant histologic findings in cervical polyps (14 of 369 cases, 3.7%) compared to previously reported studies. The increase in ASCUS and AGC Pap results was most likely related to reactive and inflammatory changes present in benign polyps. Our results suggest that removal of all cervical polyps with subsequent histologic review is warranted.

Histologic Follow-up of Women >25 Years of Age with a Cervical ThinPrep® Pap Diagnosis of ASC-H or Higher and a Negative Roche cobas® HPV DNA Test

Histologic Follow-up of Women >25 Years of Age with a Cervical ThinPrep® Pap Diagnosis of ASC-H or Higher and a Negative Roche cobas® HPV DNA Test

The Utility of Human Papillomavirus Testing in Young Women With Atypical Glandular Cells on Pap Test

This study aimed to gain information regarding the follow-up diagnoses and human papillomavirus (HPV) status of women younger than 35 years diagnosed with atypical glandular cells (AGCs) on Pap test. This is a retrospective observational study in which the cytopathology files at Fletcher Allen Health Care were reviewed from 2000 to 2013 for the diagnoses of AGC in women younger than 35 years. Subsequent pathology reports and HPV testing results were obtained. Significant lesions were defined as cervical intraepithelial neoplasia (CIN) 2 or 3, invasive squamous cell carcinoma, adenocarcinoma in situ, or adenocarcinoma. One hundred six women younger than 35 years with an AGC Pap diagnosis and subsequent follow-up were identified. Significant lesions were diagnosed in 44.3% of the women (47); the majority (55.3%, 26 patients) of which were classified as CIN 2 or 3. Adenocarcinoma in situ was diagnosed in 27.7% of the cases (13). A diagnosis of both CIN 2 or 3 and adenocarcinoma in situ was made in 14.9% of the cases (7). One patient (2.1%) was diagnosed with endometrial adenocarcinoma. The HPV status was identified in 36.8% of the women (39): 69.2% (27) was HPV positive, and 30.8% (12) was HPV negative. Fifty-five percent of HPV-positive women were diagnosed with a significant lesion upon follow-up. No known HPV-negative women were diagnosed with a significant lesion. Human papillomavirus testing may be useful in risk stratifying young women with AGC on Pap test because they are at risk of having an HPV-positive cervical lesion.

The Mystery of Atypical Glandular Cells in Cervical Cytology: Histopathologic and Clinical Correlation

Introduction: The current standard practice to help identify endometrial carcinoma (EC) on Papanicolaou (Pap) test is to document “endometrial cells in women 40 years of age” (E40). Since a significant fraction of women in this category are still menstruating, the presence of endometrial cells correlates with menstrual history and is likely not pathologic. Routine biopsy following E40 may lead to unnecessary procedures and costs. Therefore, setting a different age threshold in combination with other findings may help to guide management. Materials and Methods: A retrospective chart review was performed on consecutive EC biopsies (2007-2013) and E40 Paps (2012-2013). Clinicopathologic data included age, biopsy (reason, diagnosis, FIGO grade, time since Pap), Pap diagnosis, HPV status, and resection (diagnosis, depth of invasion, stage, and metastasis). Results: One hundred EC cases had 62 prior Pap diagnoses: negative for intraepithelial lesion (27/62), atypical glandular cells of undetermined significance (14/62), adenocarcinoma (10/62), and E40 (1/62; 51 years). 370 E40 cases had 68 biopsies (18%) and 2 hysterectomies (0.5%). E40 prompted biopsy in 26/68 (38%). 2/68 (3%) biopsied women had EC (50 and 60 years, both post-menopausal). 1/68 had complex hyperplasia with atypia (52 years; abnormal uterine bleeding [AUB]), and 3/68 had complex hyperplasia without atypia (ages 52, 40, and 58; AUB). Conclusions: Analysis of women with EC revealed 2% with E40 on prior pap testing. Analysis of E40 cases showed the majority correlated with menstrual history or did not prompt biopsy. Only 18% were biopsied, with EC in 3%. In asymptomatic women <50 years, E40 correlated with benign, non-hyperplastic endometrium. However, postmenopausal women with E40 had a risk of EC. These findings suggest that E40 diagnoses on Pap tests in asymptomatic pre-menopausal women may not warrant further work-up. Perhaps endometrial cells should only be reported in post-menopausal women or women 50 years of age.

High-risk HPV Positive Rates in Patients with Invasive Cervical Carcinoma: A Single Institution Experience

s S43 pap-HPV testing increases. Furthermore, HPV testing alone lacked detection sensitivity validating the complementary nature of the pap smear and HPV test. We also found those diagnosed with microinvasive disease were 8.3 years younger on average than those with invasive disease (38.7 vs 47 years) and the most frequent previous pap diagnosis prior to tissue confirmation was HSIL or greater. Cytology, histology, and HPV correlation table Case no. Age Tissue Last Pap Dx HPV result HPV Method Pap Dx Method 1 31 SISCa HSIL Pos HCII TP i 2 40 SqCa ASC-H&AGC Pos, 18 PCR HB SP i 3 41 SqCa HSIL, ATYEndocx Pos, 16,18 PCR HB SP i 4 49 SqCa HSIL Pos HCII TP i 5 53 SqCa NILM Pos, 16 PCR HB,16 SP i 6 37 SISCa ASC-US Neg HCII TP i 7 45 SqCa HSIL Neg HCII SP 8 64 SqCa USAT Neg HCII SP i 9 22 SISCa LSIL Pos HCII TP i 10 38 SISCa HSIL Pos HCII TP i 11 49 SqCa HSIL Pos HCII TP i 12 40 SISCa ASC-US Pos HCII TP i 13 57 SqCa ASC-H Pos HCII TP 14 41 SqCa HSIL Pos HCII TP SqCa[ Squamous cell carcinoma SISCa[superficially invasive squamous cell carcinoma

Rapid on-site cytologic examination of 1500 breast lesions using the modified Shorr’s stain

Rapid on-site evaluation (ROSE) cytology enables sample quality assessment in the procedure room and facilitates the process of examination. While its use for mammary lesions in one-stop breast clinics has been reported, its usefulness as a cytologic diagnostic tool has not been fully explored. A total of 1500 examinations of core-needle biopsy imprint/fine-needle aspiration cytology were performed for outpatients with breast lesions. The slides were immediately processed with modified Shorr's stain, which can be completed within a few minutes yet produces specimens of similar staining quality as the Papanicolaou (Pap) stain. The adequacy of sampling was evaluated on site, and a cytologic diagnosis was also made. ROSE cytologic findings were classified into five grades: class 1, inadequate; class 2, benign; class 3, indeterminate; class 4, suspicious for malignancy; class 5, malignant. If enough epithelial cells could not be obtained despite repeated examinations, the sample was scored as ineligible. These scores were utilized for patient management. Final cytologic diagnoses were made with conventional Pap stains. Reproducibility of scores between both staining methods was excellent (weighted κ statistic=0.985). When compared class by class, concordance of cytologic diagnoses was particularly high in class 2 and 5 Shorr scores, in which the agreement with Pap diagnoses was 92.8 and 93.6%, respectively. Our modified Shorr's staining protocol was useful to reduce the time for the diagnosis and treatment planning of breast lesions suspected of being breast cancer. It is beneficial for both the patients and clinicians.

Human papillomavirus DNA detection in women with normal and abnormal cervical Pap cytology

Cervical cancer is the second most common cancer in women worldwide and nearly all cases are human papillomavirus (HPV) related. Pap cytology screening has been very successful in lowering cervical cancer incidence and mortality in the US. With the increasing use of HPV DNA tests as a reflex test for ASC-US and co-testing of women over 30 for primary screening, there have been many reports of the HPV positive rates and clinical follow-up findings for women with various abnormal Pap diagnoses. This review describes the reported HPV detection rates for HSIL, LSIL, ASC-US, ASC-H, AGC, and negative Pap cytology and highlights the effect of HPV positivity on the follow-up detection of cervical lesions.

Reflex High Risk HPV Testing in Atypical Squamous Cells, Cannot Exclude High Grade Intraepithelial Lesion: A Large Institution’s Experience with the Significance of This Often Ordered Test

Objective: Cervical cytology specimens diagnosed with ASC-H consist of squamous cells with equivocal cytology for high-grade dysplastic lesions. We reviewed our cases of ASC-H with reflex HPV testing to evaluate this patient population. Study Design: We retrospectively identified patients with ASC-H in Pap smears over a 3-year period. Reflex high-risk (HR) HPV DNA testing was performed by request. Follow-up results and smear characteristics were evaluated. Results: HR HPV DNA testing was positive in 60 of 82 (73%) cases tested. The risk of high grade cervical intraepithelial neoplasia (CIN) on follow-up after a positive HPV test with ASC-H is 68.3%. The risk of high grade CIN after a negative HPV test with ASC-H is 58.3%. High grade CIN lesions were found in 20% HPV-negative patients. The cellularity of atypical cells in Pap smears was not helpful in analyzing differences in HPV-positive and HPV-negative ASC-H. Conclusion: The risk of high grade dysplasia after an ASC-H Pap diagnosis was high irrespective of the reflex HPV test results in our patient population. Therefore, our findings support the continued utilization of the current ASCCP guidelines of colposcopy and caution when utilizing reflex HR HPV testing in the colposcopy triage ASC-H patients.

The value of duplicate slides on atypical squamous cells, cannot exclude high‐grade intraepithelial lesion

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) category was added to the 2001 Bethesda System. ASC-H accounts for a small percentage (0.2-0.6%) of abnormal Pap smears and includes heterogenous group of lesions. There are more high-grade cervical lesions (30-50%) in ASC-H than ASC-US (10-15%). An accurate Pap diagnosis is crucial for appropriate patient follow-up and treatment. A total of 43 consecutive ASC-H cases were collected from October 2007 to March 2008, and all duplicate and the original slides were reviewed blindly at the end of the study. On review of the duplicate Pap slides, 18 cases had diagnostic SIL cells (15 HSIL, 2 LSIL with ASC-H, and 1 LSIL). The duplicate slides could have potentially changed 18 (41.9%) ASC-H diagnoses to a more definitive SIL diagnosis. On review of the original Pap slides, 8 of these 18 cases also had HSIL cells. Twenty-one follow-up cervical biopsies (21/43, 48.8%) showed 12 CIN 2/3, 4 CIN 1, 1 VAIN 1, 2 cervical polyps, 1 negative for dysplasia, and 1 insufficient for diagnosis. The CIN 2/3 rate was 57.1% (12/21) based on the original ASC-H Pap diagnosis. The CIN 2/3 rates were 80% (8/10) with SIL cells on duplicate slides and 36.4% (4/11) without SIL cases on duplicate slides. Our study suggested that duplicate slides were very useful for further classification of ASC-H, but other ancillary tests might be necessary for some cases. We propose a systematic approach using combined duplicate slides and reflex HPV testing to further classify ASC-H.

Evaluating the impact of human papillomavirus vaccines

While two prophylactic HPV vaccines have been proven notably efficacious in clinical trials, the effectiveness of these vaccines at the population level remains to be evaluated. To lay the foundation for understanding the strengths and limitations of different endpoints for future effectiveness research, we present a comprehensive review of HPV-related clinical outcomes, including: (i) HPV type-specific positivity and persistence, (ii) Pap diagnoses (ASC-US, LSIL, and HSIL), (iii) histologic cervical cancer precursor lesions (i.e., CIN1, CIN2, and CIN3), (iv) invasive cervical cancer (ICC), (v) anogenital warts, (vi) recurrent respiratory papillomatosis (RRP), and (vii) other HPV-associated cancers (vulvar, vaginal, anal, penile, and oropharyngeal). While research on the vaccines’ effects on these HPV clinical outcomes in the general population is presently limited, numerous large trials will soon be completed, making a priori discussion of these potential outcomes especially urgent. Furthermore, population level systems to track HPV-associated clinical outcomes may need to be developed for HPV vaccine effectiveness evaluation.

Confirmation and quantitation of human papillomavirus type 52 by Roche Linear Array© using HPV52-specific TaqMan© E6/E7 quantitative real-time PCR

Human papillomavirus type 52 is highly prevalent in Asia and Africa and accounts for 2–3% of total cervical cancer burden worldwide. The Roche Molecular Systems HPV Linear Array© (RMS-LA©) uses multiple type (i.e. mixed) probes to detect DNA from HPV 52 infection which limits the assay's ability to determine HPV 52 status in the presence of HPV 33, 35, or 58 infection. This report presents a simple to use and highly reproducible HPV 52 type-specific quantitative real-time PCR (RT-PCR) assay based on Taqman© chemistry for detection and quantification of HPV 52 DNA from cervical swab specimens. Mixed probe positive cervical swab specimens collected from rural and urban women in Thailand (n=68) were used to determine assay agreement and differences in HPV 52 DNA viral load across cytological diagnosis. Forty-eight specimens were determined to be HPV 52 positive by RMS-LA© with 94% (n=45) confirmed positive by Taqman© assay (kappa: 0.86, 95% CI: 0.74, 0.99). Higher median viral load was observed among women with a Pap diagnosis of >=ASCUS vs. normal/inflammation (8510 copies/1000 cell equivalents vs. 279 copies/1000 cell equivalents, p<0.05). Accurate ascertainment of infection status is important in understanding HPV 52's role in the etiology of cervical cancer as well as for the development of type-specific vaccines.

Validity of sampling error as a cause of noncorrelation

Sampling error is a common explanation of noncorrelation in women whose Papanicolaou (Pap) tests show high-grade intraepithelial lesions (HSIL) but whose follow-up cervical biopsies show only cervical intraepithelial neoplasia (CIN) 1, koilocytosis, or reactive/inflammatory changes. The purpose of this study was to demonstrate the validity of sampling error in this setting by determining the proportion of negative colposcopic cervical biopsies in women with HSIL who subsequently undergo cone/loop electrode excision procedure (LEEP) biopsies or repeat cervical biopsies that confirm the diagnosis of high-grade CIN (HGCIN). In all, 368 cases of HSIL were retrieved from the computerized database from January 1, 2003 to December 31, 2005. Follow-up was obtained as part of routine quality assurance/quality control activities including cytologic-histologic correlation. A total of 368 HSIL Pap diagnoses were retrieved. Of the 254 cases that were followed up by cervical biopsy, 146 showed HGCIN in the biopsy. Of the remaining 108 patients whose cervical biopsies failed to demonstrate HGCIN, 47 had a subsequent procedure, either cone/LEEP, cervical biopsy, or repeat Pap test. Cone biopsy/LEEP was performed in 34 cases (72.3%) with a diagnosis of HGCIN in 19. Repeat cervical biopsy was performed in 9 cases (19.1%) with HGCIN diagnosed in 5. Repeat Pap test was performed in 4 cases (8.5%) with HSIL diagnosed in 2. In the population of women with HSIL by Pap test followed up by cervical biopsy with or without subsequent cone/LEEP, there was a discordant cervical biopsy rate for HGCIN of 43%. In the subgroup of women with HSIL by Pap test followed up by cervical biopsy and subsequent cone/LEEP or repeat cervical biopsy, the proportion of women with negative colposcopic cervical biopsy and subsequent histology-proven HGCIN was 56%. These figures justify sampling error as a valid cause of noncorrelation in women with HSIL followed up by cervical biopsy alone.