Atypical Squamous Cells-cannot Exclude HSIL Research Articles

Evaluation of pap smears with cyto-histopathological correlation–our experience at a tertiary care hospital in Telangana

Background: The World Health Organization states that cervical carcinoma is the fourth most common cancer among women worldwide. Pap smear is the simplest and easiest test to detect this prevalent cancer at its nascent stages. Aims and Objectives: This study aims to evaluate Pap smears using the conventional method (Bethesda 2014) and correlate the abnormal smears with cervical biopsy. Materials and Methods: The study is a combined retrospective and prospective study, from January 2021 to August 2023. Pap smears received were evaluated according to Bethesda 2014. Those cases categorized as Epithelial Cell Abnormality (ECA), were correlated with corresponding histopathology on cervical biopsy. Results: Out of the 615 pap smears in this study, 525 cases (91%) were categorized as Negative for Intraepithelial Lesion or Malignancy, 53 cases (9%) as Epithelial Cell Abnormality, and 37 cases (6%) as unsatisfactory. In the Negative for Intraepithelial Lesion or Malignancy category, 353 cases (67.2%) were reactive cellular changes including inflammation, four cases (0.7%) were squamous metaplasia, and 24 cases (4.6%) were atrophic smears. In the ECA category–21 cases (39.6%) were Atypical squamous cells of undetermined significance, two cases (3.8%) were Low-grade squamous intraepithelial lesion, five cases (9.4%) were Atypical squamous cells-cannot exclude HSIL(ASC-H), 14 cases (26.4%) were High grade squamous intraepithelial lesion (HSIL) and 3 cases (5.6%) were squamous cell carcinoma (SCC) cervix, seven cases were of ECA-glandular type (13.2%). On histopathological correlation, the maximum correlation was found for HSIL and SCC cases, 71% and 100%, respectively. Conclusion: Pap smear is a crucial screening tool to diagnose cervical carcinoma at its nascent stage. This study showed a positive correlation for high-grade lesions on Pap smears.

Cervical Precancerous Lesions and Associated Factors Among Women Screened in Two Hospitals in the City of Douala, Cameroon.

Cervical cancer remains the second leading cause of death amongwomen in Cameroon despite the new strategies put in place. This study was conducted in order to determine the prevalence of precancerous cervical lesions and its associated factors in Douala (Cameroon). A cross-sectional study was conducted over a period of nine months in two hospitals of the city of Douala, Cameroon (Laquintinie Hospital and Gyneco-Ostetric and Pediatric Hospital). Cervico-vaginal and endocervical samples were taken from women attending the above-mentioned hospitals in order to identify and characterize precancerous lesions by cytological examinationand to genotype for human papillomavirus (HPV) using the Abbott RealTime High-Risk (HR) HPVkit. Data of sociodemographic characteristics, clinical history, and knowledge about cervical cancer were collected using a questionnaire. Of the 196 women included in this study, 17% had precancerous lesions, including 1.53% for atypical glandular cells (AGC), 4.53% for atypical squamous cells (ASC), 4.53% for low-grade squamous intraepithelial lesion (LSIL), 5.61% for high-grade squamous intraepithelial lesion (HSIL), 0.51% for atypical squamous cells of undetermined significance (ASC-US), and 0.51% for atypical squamous cellscannot exclude HSIL (ASC-H). In addition, the prevalence of HPV infection was 18%, of which 2% was for HPV 16, 2% for HPV 18, and 14% for undetermined HPV. A positive association was recorded between the occurrence of precancerous lesions and HPV infection (P=0.01), age, and school level. Moreover, the occurrence of precancerous lesions was positively associated with the participants' level of knowledge (P=0.01). Precancerous lesions were predominantly HSIL, and the factor most associated with these lesions was HPV infection. This study demonstrates that diagnosis is made at a relatively late stage due to a low level of knowledge about cervical cancer in the population.

Prevalence of high risk human papilloma virus among Iraqi women with abnormal cervical cytology

Persistent infection with high-risk human papilloma virus (HPV) has been recognized as the primary etiological agent for the development of premalignant and malignant cervical lesions. Cervical cancer represents a major health problem among female especially in developing countries. This study was designed to determine the prevalence of oncogenic HPV genotypes among Iraqi women who had abnormal cytological findings by using endpoint multiplex PCR. Fifty cervical swab specimens were collected from women complaining from gynecological problems and another thirty specimens obtained from apparently healthy women as a control group. Cytological examination showed that lesions in the forms of atypical squamous cells of undetermined significance (ASCUS), low grade squamous intraepithelial lesions (LSIL), high grade squamous intraepithelial lesions (HSIL), atypical squamous cells cannot exclude HSIL (ASC-H), non-specific cervicitis and squamous cervical cancer were observed in 30%, 24%, 20%, 4%, 16% and 6%, respectively. High-risk HPV DNA was detected in 19% among women population with the oncogenic HPV-16, -18 and -58 were being the most prevalent high risk genotypes among women at frequencies of 26.7%, 13.3% and 13.3%, respectively. The detection of high-risk HPV and its association with the ASC-US lesions may serve as a prognostic factor prior to cervical cancer disease progression.

Human papillomavirus infection and anal cytology in Taiwanese homosexual men with and without HIV infection.

Anal cancer screening has not been adopted by Taiwanese care providers. The study aim was to explore the differences of anal cytology and HPV detection among men with and without HIV. In this case-control study, men with HIV who attended one of the outpatient clinics of Taoyuan General Hospital were enrolled as cases. Men who had experienced condomless sex and tested HIV negative were enrolled as controls. Anal swabs were collected for thin-preparation anal cytology and HPV genotyping. A total of 288 men who had tested positive for HIV and 208 who had tested HIV negative were enrolled; 75% of subjects with HIV and 30.3% of those without HIV had tested positive for various types of HPV (P < 0.001). Anal cell dysplasia, including atypical squamous cells with undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs), or atypical squamous cells cannot exclude HSIL (ASC-H), were noted in 20.8% of men with HIV and 4.8% of those without HIV (P < 0.001). In multivariate analysis, HIV serostatus, history of sexually transmitted infections, having male sexual partners, and practice of anal sex were correlated significantly with detection of any type of HPV. Additionally, both oncogenic and non-oncogenic HPV types were significantly associated with anal cytology dysplasia. We strongly suggest that there should be awareness of anal HPV infection and related anal cellular dysplasia in at-risk populations.

Systemic cervical cytology training and quality control programs can improve the interpretation of Papanicolaou tests

There is no national cervical screening program or national standards for cervical cytology quality control in China. Since 2013, systematic training and quality control programs were implemented in the Papanicolaou testing process at Jinan KingMed Diagnostics. Pathologists were required to complete 1 year of cytology study in the KingMed Diagnostics Cytology School, including 6 months of a diagnostic course and 6 months of practical training in the clinical laboratory. In this study, we compared the Papanicolaou abnormal reporting rates before and after the implementation systematic training and quality control programs. Systematic cytology training and quality control (QC) programs were implemented in 2013. Results from 997,162 cases of liquid-based cytology (LBC) and 100,066 cases of conventional Papanicolaou smears (CPS) rendered between 2008 and 2015 at Jinan KingMed Diagnostics were collected and analyzed. After implementation of training and programs, the abnormal reporting rates of atypical squamous cells of unknown significance (ASC-US), low-grade squamous intraepithelial lesions (LSIL), atypical squamous cells cannot exclude HSIL (ASC-H), atypical glandular cells (AGC), and high-grade squamous intraepithelial lesions (HSIL) in LBC were significantly increased. Similar trends were also observed in CPS reporting, except for ASC-H, squamous cell carcinoma, and AGC, probably due to the small percentages of these categories. The study demonstrates the importance of the formal cytology training and QC programs to ensure standardized and effective cervical cancer screening in undeveloped countries, which account for the largest percentage of the world's annual incidence of cervical cancer and with a largely unscreened population.

A Large Retrospective Study of 12714 Cases of LEEP Conization Focusing on Cervical Cancer That Colposcopy-Directed Biopsy Failed to Detect.

Punch biopsy is important in the diagnosis of cervical cancer. However, it may fail to detect early cervical cancers. A retrospective study was performed in the largest academic women's hospital in China to demonstrate cervical cancer that colposcopy-directed biopsy failed to detect. Methods. Patients who were diagnosed with high-grade squamous intraepithelial lesion (HSIL), adenocarcinoma in situ (AIS), and persistent low-grade squamous intraepithelial lesion (LSIL) via colposcopy-directed biopsy and had further undergone loop electrosurgical excision procedure (LEEP) conization were included. These procedures were performed at Obstetrics and Gynecology Hospital of Fudan University from July 1, 2013, to December 31, 2016. In total, 5.98% (760/12714) of patients who underwent conization were diagnosed with invasive cervical cancer. Persistent LSIL (0.24%), HSIL (6.37%), and AIS (24.31%) were detected cancer by conization. Histological subtypes included squamous cell carcinoma (92.0%), adenocarcinoma (5.1%), adenosquamous carcinoma (1.8%), adenoid basal type carcinoma (0.9%), and small cell neuroendocrine carcinoma (0.1%). Cytology reports consisted of HSIL (45.4%), atypical squamous cells of undetermined significance (ASC-US) (16.1%), and LSIL (11.6%), and atypical squamous cells cannot exclude HSIL (ASC-H) (9.3%), squamous cell carcinoma (0.9%), AGC (atypical glandular cells, 0.9%), AIS (0.4%), and NILM (negative for intraepithelial lesion or malignancy, 15.4%). The sensitivity of high-risk human papillomavirus (hrHPV) screening (96.4%) was significantly higher than that of cytology (84.6%) (P < 0.01), with sensitivity of cotesting at 99.8% and a ratio of double-negative results at 0.2%. The sensitivity of cytology and hrHPV screening of different cervical cancer histologic subtypes was also demonstrated. In this large retrospective study, we systematically reported the cytology, hrHPV, pathology, and stages of cervical cancer that colposcopy-directed biopsy failed to detect.

Cell Abnormality in Pap Smear in Women with Postmenopausal Bleeding

Cancer cervix is a preventable and curable disease due to effective screening methods. Uterine cervix is ideal for screening due to easy accessibility for inspection, palpation and exfoliative cytology. The Pap smear is a screening test for cervical cancer, and with appropriate follow-up it can reduce cervical cancer incidence by up to 80%. This study includes fifty peri and postmenopausal women, cervical smears were taken in the Out-patient Clinic of Gynecology and Obestetrics Department and Pap stain was used for each sample, and the criteria of Bethesda (2014) was used for the diagnosis of each case. Bleeding was the main complaint in 92% patient and the remaining 8% complained from vaginal discharge and itching. Thirty nine patients were negative for intraepithelial lesion or malignancy (non-neoplastic), eight showed neoplastic changes, and 3 samples were insufficient for cytological interpretation. Two out of the 8 cases showed neoplastic lesions were atypical squamous cells of undetermined significance (ASCUS), two diagnosed as atypical squamous cells cannot exclude HSIL (ASC-H), 3 were high grade squamous intraepithelial lesions (HSIL) and one cases had features of squamous cell carcinoma (SCC). Six out of 39 samples showed only pure atrophy, three showed follicular cervicitis, three had features suggestive of Tichomonas vaginalis infection, one diagnosed as HSV infection, one showed bacterial vaginosis and eleven cases showed nonspecific inflammation. Non-neoplastic cases included also six cases showed metaplastic changes and eight had normal cytological findings. Conclusion: cervical smears is important in early detection of cervical carcinoma and its precursors in Sohag community as an easy, costless, accessible, and reliable manner and Bethesda system (2014) is beneficial for accurate diagnosis.

Ability to detect high-grade squamous anal intraepithelial lesions at high resolution anoscopy improves over time.

Background Anal cancer is increasing in incidence, has very high rates in specific populations and shares many similarities with cervical cancer. High-grade squamous intraepithelial lesions (HSIL) are regarded as precursors to anal cancer. High resolution anoscopy (HRA), which is derived from colposcopy, is the only currently available tool that can identify areas of the anal canal for targeted biopsy and identification of HSIL. This study investigated the ability over a period of time of a single anoscopist to identify and adequately biopsy HSIL, correlating with contemporary anal cytological findings. Four hundred paired cytology and histology samples collected from 283 patients over a 7-year period from 2004 to 2010 were compared. There was a significant increase in HSIL detection rates when anal squamous cells of undetermined significance (ASC-US; 38.6-66.0%) or low-grade squamous intra-epithelial lesion (38.8-68.3%) were taken as cut-off points (P<0.001 for both). Detection rates did not change significantly when atypical squamous cells-cannot exclude HSIL (ASC-H) or a higher grade lesion (70-76.6%) was taken as the cut-off point. The increase in ability to detect histological HSIL over time and with increasing experience has the potential to impact on delivery of clinical services and the interpretation of clinical trial data. Further studies are required to determine the extent of this effect on other clinicians practising HRA.

Cytological Diagnoses of Adenocarcinoma in situ of the Cervix: Common Misdiagnoses

Objective: In routine screening, glandular lesions have high false-negative and false-positive rates. Our study sought to improve the cytological diagnoses and differentiation of glandular lesions. Study Design: A total of 24 cytology slides were retrospectively reviewed. Among these slides, 15 were confirmed via histology to have varying amounts of adenocarcinoma in situ (AIS) components. The other 9 cytology slides exhibited AIS mimics that had been originally considered to be AIS or atypical glandular cells (AGCs) and were selected for differentiation from AIS. Results: Overall, 12 of the 15 cytological slides exhibited significant atypical glandular features that met the criteria for AIS. However, the original cytological diagnoses included 2 cases of AIS, 3 AGCs-favor neoplasia (AGC-FN), 2 AGCs, 1 case that was not otherwise specified (AGC-NOS), 1 NILM (negative for intraepithelial lesion and malignancy), 3 HSILs (high-grade squamous intraepithelial lesions), and 2 ASC-Hs (atypical squamous cells, cannot exclude HSIL). The latter 9 cytological slides were subsequently histologically confirmed to be 2 metaplasias, 2 reactive lesions, 1 decidual change, 3 serous adenocarcinomas, and 1 SCNEC (small-cell neuroendocrine carcinoma). Conclusion: Cytological screening will be valuable for identifying glandular lesions as effectively as squamous lesions if the doubly high false rates can be decreased.

Expression of Molecular Markers and Risk Categorization in Pre-neoplastic and Non-neoplastic Cervical Lesions

Worldwide, cervical cancer is the fourth most common cancer in women [1]. It is preceded by many stages of pre-neoplastic lesions classified as Atypical squamous cells of undetermined significance (ASC-US) / Atypical squamous cells cannot exclude HSIL (ASC-H), Low-grade squamous intraepithelial lesion (LSIL), and High-grade squamous intraepithelial lesion (HSIL) (Bethesda, 2001). However, a large proportion of cases of epithelial malignancy arise from apparently normal cell and also from the LSIL where as many HSILs remain static for many years [2]. In this study, many important markers and epidemiological parameters Pap smears were examined to look for high risk cases of cervical non-malignant lesions. Methods: A total of 60 cases and controls were selected by colposcopic examination and smears were collected. Slides were used for immunohistochemical staining for four markers: p53, Ki-67, PCNA and CEA and PAP stain. All experimentally generated data were analyzed by Epi Info (TM) 3.5.3. Results: Expression of PCNA, p53, Ki-67 and CEA were significantly associated with both in Epithelial Cell Abnormalities (ECA) and Negative for Intraepithelial Lesion or Malignancy (NILM). Among HSIL, LSIL and ASCUS, HSIL was more common in Muslim women in comparison to Hindus. Whereas inflammatory lesions like RCC and RCCI were more common in Hindu population. Muslim women have a more normal Cytopathology smear than Hindus. Conclusions: Both the NILM and ECA cases carry risk for cancer conversion. Women with High grade Squamous Intraepithelial lesion or HSIL with PCNA, p53, Ki-67 and CEA strong positivity may have a higher risk of developing cervical cancer.

Limitations on the detection rate of high-risk HPV by hybrid capture 2 methodology in high grade intraepithelial (HSIL) or atypical squamous cells-cannot exclude HSIL (ASC-H) cytological lesions with proved CIN2.

Recent literature data suggest that the high-risk human papillomaviruses (HR-HPVs) testing with several molecular techniques could be an alternative to cytology in the detection of cervical intraepithelial neoplasias of grade 2 or worse (CIN2+). However, any molecular techniques have its own limits and may give false negative results which must be clearly known before undertaking a primary HPV screening. This study aims to evaluate the performance of the high-risk HPV hybrid capture II detection kit (HCII) which is considered as a “gold standard technique” in a series of 100 women having proved both cytological lesions of atypical squamous cells-cannot exclude an HSIL (ASC-H) or high-grade squamous intraepithelial lesion (HSIL) and histological lesions of CIN2+. The clinical sensitivity of HCII in women with a cytological diagnosis of ASC-H/HSIL and a diagnosis of CIN2+ is high but not absolute and estimated at 96% (95,6% and 100% of women with a diagnosis of CIN2/3 or invasive squamous cell carcinoma, resp.). These data although they are infrequent must be clearly referred before to start an HPV primary screening of CIN2+ especially with HCII methodology.

Performance of Siriraj Liquid-Based Cytology: a Single Center Report Concerning over 100,000 Samples

To evaluate the performance of Siriraj liquid-based cytology (LBC) for cervical neoplasia screening after increasing use of this technology. Cytological reports of 103,057 Siriraj-LBC specimens obtained in 2007-2009 were compared with those of 23,676 specimens obtained in 2006. Comparing with the year 2006, the 2007-2009 patients were slightly older (43.4 ± 12.yr vs 42.7 ± 12.2 yr, p <0.001), and their specimens had much lower proportion of unsatisfactory slides (OR=0.06, 95%CI 0.04-0.09) with comparable detection rates (3.96% vs 3.70%, p=0.052) but different proportions of various cytological abnormalities (p<0.001). The 2007-2009 Siriraj-LBC had a negative predictive value (NPV) for cervical intraepithelial neoplasia 2+ (CIN2+) of 97.6% and an overall positive predictive value (PPV) of 43.9%. The PPV for CIN2+ varied with types of abnormal cytology, from 13.7% to 93.8% in atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells cannot exclude HSIL (ASC-H), high-grade squamous intraepithelial lesion (HSIL), atypical glandular cells (AGC), to squamous cell carcinoma (SCC), respectively. The PPVs for CIN2+ in ASCUS and LSIL were comparable, but the PPV for CIN1 was higher for LSIL than for ASCUS (41.63% vs 16.32%). Siriraj-LBC has demonstrated a stable detection rate and NPV for CIN2+ of >95% since the first year of use. The comparable PPVs for CIN2+ of ASCUS and LSIL suggests that these two conditions may undergo similar management; other cytological abnormalities need immediate evaluation.

Low-Grade Squamous Intraepithelial Lesion/Cannot Exclude High-Grade Squamous Intraepithelial Lesion (LSIL-H) Is a Unique Category of Cytologic Abnormality Associated With Distinctive HPV and Histopathologic CIN 2+ Detection Rates

To examine data correlating high-risk human papillomavirus (hrHPV) results in patients with both low-grade squamous intraepithelial lesion (LSIL) and atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) cytology findings (LSIL-H) with follow-up histopathology. A total of 494 LSIL-H ThinPrep (Hologic, Marlborough, MA) cases with hrHPV testing were identified. Histopathologic follow-up was available in 347 patients. Among 347 patients with follow-up histopathology after LSIL-H cytology and hrHPV testing, 90.5% tested hrHPV positive. Cervical intraepithelial neoplasia (CIN) 2/3 was diagnosed in 29.4% and CIN 1 in 53.6%. CIN 2/3 was diagnosed in significantly more patients with hrHPV-positive LSIL-H than following hrHPV-negative LSIL-H results. Compared with published institutional data, LSIL-H had significantly lower hrHPV and histopathologic CIN 2/3+ rates (90.5% and 29.4%, with no cervical cancers) than high-grade squamous intraepithelial lesion (HSIL) (95.7% and 70.5%, with 2.4% cervical cancers) but higher rates than LSIL (80.2% and 12.9%) or atypical squamous cells/cannot exclude HSIL (ASC-H) (54.3% and 17.2%). Whereas CIN 2/3 detection rates were similar in HPV-positive LSIL-H and HPV-positive ASC-H, CIN 2/3 findings were more likely with HPV-negative LSIL-H than with HPV-negative ASC-H. LSIL-H is a unique category of cytologic abnormality associated with distinctive hrHPV and CIN 2/3+ diagnostic rates.

3q26 Gene Amplification in a Woman With Abnormal Cervical Cytology Unconfirmed by Cervical Biopsies

Patient: A 28-year-old Caucasian female. Chief Complaint: Multiple abnormal Pap tests unconfirmed by cervical and endocervical biopsies. History of Present Illness (see Table 1): In 2008 the patient was diagnosed with a low-grade squamous intraepithelial lesion (LSIL) by ThinPrep Papanicolaou test (Pap test). Over the next 2.5 years, multiple ThinPrep Pap assessments showed increasing severity of cellular changes from “atypical squamous cells cannot exclude HSIL (ASC-H)” to “high-grade squamous intraepithelial lesion (HSIL)” (Image 1). During this period 4 successive cervical biopsies and endocervical curettings, however, revealed only benign squamous mucosa, squamous metaplasia, reactive squamous atypia, and benign endocervix. The only exception was a small number of cells suspicious for a squamous intraepithelial lesion (SIL) (dysplasia) present in the endocervical curettings performed in May 2010. Multiple tests performed during these 2.5 years were positive for high-risk human papillomavirus (HPV). From February 2009 to January 2011, 4 colposcopic examinations, done at 6-month intervals, showed an area of acetowhite epithelium at the 11–12 o’clock position of the cervix. The colposcopies were judged to be satisfactory with complete visualization of the cervical-endocervical transition zone. In June 2011 an automated fluorescense in situ hybridization (FISH) assay for detection of 3q gain in HPV infected cervical cells ( onco FISH cervical test, Ikonisys Clinical Laboratory, New Haven, CT) was positive, showing 2 nuclei with at least 5 copies of 3q26 (Image 2). Two months later a cervical loop electrosurgical excision procedure (LEEP), encompassing the acetowhite epithelium and surrounding tissue, was performed. Histological examination revealed a very …

Quantitative detection of screening for cervical lesions with ThinPrep Cytology Test

OBJECTIVE To investigate the available parameters in gynecological screening for cervical lesions by liquid-based cytology technology (ThinPrep Cytology Test, TCT) and The Bethesda System (TBS), also with computer image analysis. METHODS With application of the image analysis system, all grades of cervical lesion cells were detected quantitatively and sorted in atypical squamous cells of undetermined significance (ASCUS), atypical squamous cells-cannot exclude HSIL (ASC-H), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and cervical squamous cell carcinoma (SCC) with the mean optical density (MOD), average grey (AG), positive units (PU), and nucleus to cytoplasmic ratio (N:C). Differences between each group of cells were compared and analyzed statistically. RESULTS Apart from four stereologic parameters in LSIL and HSIL groups there were no di? erences among them, in the other groups, there was statistically significant in differences between MOD, AG and PU values. Differences between them in the ratio of nucleus to cytoplasm were highly statistically significant. CONCLUSION Stereological indexes may serve as a screening tool for cervical lesions. The image analysis system is expected to become a new means of cytological assisted diagnosis.

The significance of “low-grade squamous intraepithelial lesion, cannot exclude high-grade squamous intraepithelial lesion” as a distinct squamous abnormality category in Papanicolaou tests

Early cytologic detection and treatment of high-grade squamous intraepithelial lesion (HSIL) is critical to cervical cancer prevention. The term atypical squamous cells (ASC), cannot exclude HSIL (ASC-H) was introduced in 2001 in the Bethesda System (TBS 2001) to define changes suggestive, but not diagnostic, of HSIL in the absence of unequivocal squamous intraepithelial lesion (SIL). Previous studies showed that women with ASC-H cytology are at an increased risk of harboring underlying histopathologic HSIL. TBS 2001, however, did not address the significance of finding ASC-H changes in a background of unequivocal low-grade SIL (LSIL). There may be a tendency for cytologists to lump these changes with either LSIL or HSIL, depending on their level of comfort. In their laboratory, the authors have referred to these changes as "LSIL, cannot exclude HSIL" (LSIL-H). Between July 2001 and July 2003, all Papanicolaou (Pap) tests that were obtained by using the ThinPrep technique were retrieved from the computer data base at the authors' institution. All categories of squamous cell abnormalities, including LSIL-H, were evaluated for their incidence and follow-up diagnoses of HSIL and more severe lesions (HSIL +). All patients had a minimum of 2 year follow-up by biopsy and cytology (range, 2-4 years). LSIL-H comprised 0.15% (n = 194) of all Pap tests (n = 129,911) that were evaluated during the study period. Follow-up biopsy was available on 59 patients (30.4%), which showed HSIL + in 40.7% of patients. This rate of associated HSIL + differed significantly from that of LSIL (13%; P < .001) and HSIL (74%; P < .001), but was similar to that of ASC-H (44.6%). The results from this study showed that patients with cytologic diagnoses of LSIL-H had an intermediate risk of harboring histopathologic HSIL +. This risk was similar to ASC-H but fell between the low risk associated with ACS-US and LSIL and the high risk associated with HSIL cytologic diagnoses. The authors believe that LSIL-H should be considered as a distinct cytologic diagnostic interpretation and should be separated from LSIL and HSIL. Although LSIL-H does not represent a unique biologic entity, it has clinical usefulness because of its high positive predictive value for HSIL + lesions.