Atypical Squamous Cells of the Cervix

Morphological abnormalities of the cervical EPITHELIUM, usually revealed in PAP SMEAR, which do not meet the criteria for squamous CERVICAL INTRAEPITHELIAL NEOPLASIA or SQUAMOUS CELL CARCINOMAS of the CERVIX . It may be a sign of infection with certain types of human papillomavirus (HPV).or sign of a benign (not cancer) growth, such as a cyst or polyp or, in menopausal women, of low hormone levels. More testing, such as HPV test, may be needed.

Also Known As:

ASC Atypical Squamous Cells; ASC-H Atypical Squamous Cells, Cannot Rule Out High-Grade Squamous Intra-epithelial Lesion; ASC-US; ASCUS; Atypical Cervical Squamous Cells; Atypical Squamous Cells of Undetermined Significance; Atypical Squamous Cells, Cannot Rule Out High-Grade Squamous Intra-Epithelial Lesion; ASC H Atypical Squamous Cells, Cannot Rule Out High Grade Squamous Intra epithelial Lesion; Atypical Squamous Cell; Atypical Squamous Cells, Cannot Rule Out High Grade Squamous Intra Epithelial Lesion; Cell, Atypical Squamous; Cells, Atypical Squamous; Squamous Cell, Atypical; Squamous Cells, Atypical; Atypical Squamous Cells

Networked: 685 relevant articles (23 outcomes, 87 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Atypical Squamous Cells of the Cervix
2.	Squamous Intraepithelial Lesions
3.	Uterine Cervical Dysplasia
4.	Uterine Cervical Neoplasms (Cancer of the Cervix)
5.	Endometrial Neoplasms (Endometrial Cancer)

Experts

1.	Schiffman, Mark: 21 articles (01/2022 - 01/2002)
2.	Arbyn, Marc: 14 articles (01/2019 - 08/2006)
3.	Castle, Philip E: 13 articles (01/2022 - 01/2002)
4.	Solomon, Diane: 12 articles (05/2009 - 06/2003)
5.	Wentzensen, Nicolas: 9 articles (01/2022 - 02/2007)
6.	Jeronimo, Jose: 9 articles (01/2017 - 06/2005)
7.	Wheeler, Cosette M: 9 articles (12/2016 - 03/2002)
8.	Bergeron, Christine: 7 articles (01/2019 - 01/2006)
9.	Cuzick, Jack: 6 articles (12/2016 - 02/2007)
10.	Massad, L Stewart: 6 articles (07/2009 - 04/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Atypical Squamous Cells of the Cervix:

1.	DNA (Deoxyribonucleic Acid)IBA 06/01/1998 - "The in situ detection of HPV DNA in ASCUS Pap smears with a corresponding biopsy-proven squamous intraepitheal lesion (SIL) within 6 months was significantly greater (14 of 21, 67%) than in smears with corresponding biopsy specimens were negative for SIL (2 of 19, 10%) (p < 0.05). " 03/01/2013 - "Risk stratification revealed that HPV DNA testing was not beneficial for HSIL cases, whereas it was for ASCUS and, in some combinations, for negative and LSIL cytology. " 05/01/2017 - "In total, 591 patients with ASCUS underwent HPV DNA screening, with 455 and 136 having positive and negative results, respectively; 252 patients with positive results and 66 with negative results underwent biopsy and histology testing and were included in the study. " 03/01/2006 - "Cervical/endocervical cytology screening has decreased morbidity and mortality, and implementing adjunctive human papilloma virus (HPV) DNA testing for atypical squamous cells of undetermined significance has improved the specificity for detecting premalignant squamous lesions. " 09/01/2005 - "Our findings suggest that reflex HPV DNA testing would be helpful in triaging patients diagnosed with ASC-US. "
2.	VaccinesIBA 12/20/2014 - "Vaccine efficacy against atypical squamous cells of undetermined significance or greater associated with HPV 16/18 was also significant. " 03/01/2021 - "Although 78.5% of ICC and 60.3% of HSIL cases were attributed to 9-valent vaccine genotypes, the other genotypes not covered by any vaccine still resulted in increases in coverage, with 1.5% for ICC, 5.3% for HSIL, and 13.5% for ASCUS/LSIL. " 05/01/2019 - "37% (28/76) of women with positive cytology results (ASCUS+) had a type not included in the basic vaccine and 25% (19/76) had a type not currently in the nine-valent vaccine. " 03/01/2012 - "The number of prevented cases of ASCUS, CIN1, CIN2, CIN3 and CC when vaccine was used was 322 791, 303 050, 92 496 and 11 827, respectively. " 10/01/2016 - "Vaccine efficacy against HPV 16/18-related cytological abnormalities (atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion) and CIN1+ was also significant. "
3.	Insulin-Like Growth Factor II (Somatomedin A)IBA 12/01/2003 - "Serum IGF-II and IGF-BP3 levels were measured, using ELISA kits (Diagnostic Systems Laboratories), in 23 controls; 16 ASC-US with normal biopsies; 14 ASC-US with advanced CIN; 2 pretherapy CIN-I; 8 successfully treated CIN-I; 24 persistent CIN I; 14 pretherapy CIN II/III; 10 posttherapy CIN II/III with normal biopsies; 18 persistent CIN-II/III; 7 with pretherapy cervical cancer; 19 with posttherapy cervical cancer under remission; 15 with posttherapy persistent/recurrent cervical cancer; 10 with persistent ovarian or endometrial cancer; and 3 with endometrial or vulvar with cervical cancer. " 09/01/2005 - "(a) As anticipated, serum IGF-II levels were elevated as early as ASCUS with CIN on biopsy and continued to be elevated in CIN (all grades; pre-therapy and persistent) and cervical cancer (pre-therapy, early, late and persistent). " 12/01/2003 - "Compared to controls (493 +/- 90 ng/ml) and women with other gynecological cancers, serum IGF-II levels were significantly increased in women with ASC-US, with advanced CIN on biopsy (P < 0.0001), persistent CIN-I (993 +/- 262 ng/ml; P < 0.0001), pretherapy advanced CIN (1086 +/- 240; P < 0.0001), pretherapy cervical cancer patients (1746 +/- 318 ng/ml; P < 0.0001) and posttherapy persistent/recurrent CIN (1094 +/- 300; P < 0.0001); and cervical cancer (1395 +/- 189; P < 0.0001). " 09/01/2005 - "Serum IGF-II levels were normal in ASCUS with normal biopsy, successfully treated CIN-I, II/III, cervical cancer as well as pre-therapy ovarian and endometrial cancers (therapy efficacy: P < 0.0001 by chi-square analysis). " 01/01/2005 - "Serum IGF-II test helps in diagnosing cervical cancer as early as ASC-US or cervical intraepithelial neoplasia (CIN)-I and in monitoring therapy efficacy (p < 0.001 by Student's 't' test and Chi-square analysis). "
4.	Acetic Acid (Vinegar)FDA LinkGeneric 07/01/2009 - "To simulate colposcopic assessment, we obtained digitized cervical images at enrollment after acetic acid application from 919 women referred for equivocal or minor cytologic abnormalities into the ASCUS-LSIL Triage Study. " 06/01/2008 - "Digitized cervical images from 862 women enrolled in the ASCUS-LSIL Triage Study were obtained after application of 5% acetic acid. " 10/01/2007 - "Twenty expert colposcopists evaluated 939 digitized images of the uterine cervix obtained after the application of 5% acetic acid during the ASCUS-LSIL Triage Study. " 11/01/2015 - "When the test was calibrated to have similar specificity, sensitivity of the combined tri-marker test for CIN2+ was comparable with cytology [atypical squamous cells of undetermined significance or worse] (89% and 95%, respectively) and superior to visual inspection with acetic acid (85% vs 70%) and HPV16/18 genotyping (65% vs 40%). " 01/01/2008 - "The sensitivity of cervical cytology (with a result of >or= ASC-US) was 53.6% (95% CI: 42.1, 65.0) compared with 52.9% (95% CI: 43.5, 62.5) for visual inspection with acetic acid and 90.3% (95% CI: 76.2, 98.7) for Hybrid Capture II (with result of >1 relative light units). "
5.	Cyclin-Dependent Kinase Inhibitor p16IBA 10/25/2012 - "The published literature indicated the improved accuracy of p16(INK4a) compared with HC2 testing in the triage of women with ASC-US. " 05/08/2017 - "目的：探讨p16(INK4a)/Ki-67双免疫细胞化学染色法对宫颈细胞学结果为不能明确意义的不典型鳞状细胞(ASCUS)和低级别鳞状上皮内瘤变(LSIL)患者的分流作用。方法：收集2014年4月至2015年2月宫颈液基细胞学结果为ASCUS(318例)或LSIL(102例)的420例患者资料，包括剩余细胞学样本、高危人乳头状瘤病毒(HPV)检测结果、活检结果和随访资料，采用p16(INK4a)/Ki-67双免疫细胞化学染色法检测细胞学样本。以活检结果为参照，比较p16(INK4a)/Ki-67双免疫细胞化学染色法和高危HPV检测法筛查宫颈癌前病变或宫颈癌[包括宫颈上皮内瘤变(CIN)2、CIN3、原位癌及浸润性癌，简称为CIN2＋]的灵敏度和特异度。结果：采用宫颈细胞学筛查CIN2＋时，p16(INK4a)/Ki-67双免疫细胞化学染色法与高危HPV检测相比，灵敏度略低(84.2%比94.7%)，特异度较高(84.0%比53.9%)。在ASCUS患者中，p16(INK4a)/Ki-67双免疫细胞化学染色法与高危HPV检测的灵敏度分别为82.6%和91.3%，特异度分别为88.8%和63.7%；在LSIL患者中，p16(INK4a)/Ki-67双免疫细胞化学染色法与高危HPV检测的灵敏度分别为86.7%和100.0%，特异度分别为67.8%和20.7%。在<30岁患者和≥30岁患者中，p16(INK4a)/Ki-67双免疫细胞化学染色法的特异度均较高(80.8%和84.5%)，而高危HPV检测的特异度明显较低，分别为42.3%和56.9%。结论： p16(INK4a)/Ki-67双免疫细胞化学染色对于筛查宫颈细胞学样本CIN2＋兼具较高的灵敏度和特异度，其特异度高于高危HPV检测，能有效分流细胞学ASCUS或LSIL中的高危人群。对于年龄<30岁的女性患者，p16(INK4a)/Ki-67双免疫细胞化学染色法可能是一个潜在的细胞学联合筛查或初筛工具。." 05/08/2017 - "Conclusions: p16(INK4a)/Ki-67 double immunostaining can effectively identify the high risk population in ASCUS or LSIL, with higher specificity than high risk HPV test. " 05/08/2017 - "For ASCUS patients, the sensitivity of p16(INK4a)/Ki-67 double immunostaining and high risk HPV was 82.6% and 91.3%, and the specificity was 88.8% and 63.7%, respectively. " 05/08/2017 - "Results: Further screening CIN2+ in cytology ASCUS and LSIL group , the sensitivity of p16(INK4a)/Ki-67 double immunostaining was slightly lower than high risk HPV (84.2% vs. 94.7%), while the specificity was higher (84.0% vs. 53.9%). "
6.	Vaginal Creams, Foams, and Jellies (Vaginal Tablet)IBA 06/20/2023 - "This study aimed to investigate the preventive effect of a vaginal gel on p16/Ki-67-positive abnormal cytological cervical findings (ASC-US, LSIL) and hr-HPV in women. " 07/29/2023 - "HPV-positive women ≥ 25 years with ASCUS/LSIL cervical cytology results and concordant colposcopy images were included, receiving the vaginal gel one cannula/day for 21 days (first month) + one cannula/alternate days (five months). " 01/01/2021 - "The examined vaginal gel may support the healing of conspicuous cytological findings (ASC-US, LSIL, ASC-H, or HSIL) and clearance of hr-human papillomavirus positive results." 06/20/2023 - "Successful Preventive Treatment of Oncogenic Transforming HPV Infections in Low-Grade Cytology (ASC-US/LSIL) Patients with an Adsorptive and Antioxidant Vaginal Gel." 09/01/2002 - "One hundred forty-five patients whose initial Papanicolaou smears were limited by inflammation or benign cellular changes, reactive cellular changes, or atypical squamous cells of undetermined significance that did not favor a neoplastic process were randomized to 5 days of treatment with 0.75% metronidazole vaginal gel or to a control group receiving no treatment. "
7.	Folic Acid (Vitamin M)FDA LinkGeneric 02/01/2017 - "Folate receptor-mediated epithelium staining had moderate agreement with cytology thresholded at atypical squamous cells, unable to exclude a high grade intra-epithelial lesion and was more sensitive that the later (85.7% vs 74.5% for intra-epithelial neoplasia grade 2 and worse; 89.2% vs 75.4% for intra-epithelial neoplasia grade 3 and worse). " 09/01/2020 - "To evaluate the efficacy of folate receptor-mediated tumor detection (FRD) for identifying high-grade intraepithelial squamous lesions (HSIL) in the triage of women who are positive for human papillomavirus (HPV), and those with cytology findings of atypical squamous cells of undetermined significance (ASCUS). " 07/01/2011 - "The serum folate levels in all patient groups [HSIL 10.0 ± 0.4 ng/ml, low-grade squamous intraepithelial lesion (LSIL) 10.6 ± 0.5 ng/ml, atypical squamous cells-undetermined significance (ASCUS) 11.1 ± 0.8 ng/ml] were lower than control group (11.9 ± 0.5 ng/ml; p < 0.05). " 01/01/2021 - "The aim of this prospective cohort trial was to analyze the association between presence of ASCUS and HPV persistence with folate and vitamin B12 levels. " 01/01/2021 - "The positivity of HPV in women with ASCUS is associated with low serum vitamin B12 and folate levels."
8.	A-Form DNA (A-DNA)IBA 10/01/2022 - "The findings of the present study will contribute toward identifying a DNA methylation marker for the early detection of abnormal samples before they reach the initial stages of cervical cancer, and should prove to be helpful for clinicians in terms of diagnosing patients whose cells are ASC US.<br />." 04/25/2003 - "Six of 12 (50%) of the high-risk HPV-positive ASCUS cases presented isolated cells with a DNA content above 5c, whereas cells with a DNA content above 9c were found in 3 of 12 cases (25%) and were exclusively found in combination with high-risk HPV infection. " 09/01/2006 - "A total of 573 liquid-based cytology samples were tested for the presence of HPV by a DNA enzyme immunoassay; 210 were found to be positive for HPV DNA and were evaluated using both genotyping assays (163 with normal cytology, 22 with atypical squamous cells of undetermined significance, 20 with mild/moderate dysplasia, and 5 with severe dysplasia). "
9.	Biomarkers (Surrogate Marker)IBA 02/25/2007 - "The authors investigated the efficacy of p16INK4a as a biomarker to identify samples of patients with HGCIN among those with an ASCUS or LSIL result in Papanicolaou cytology. " 01/01/2011 - "Discussion: 'Testing for biomarkers after ASC-US Pap smears' by Lin et al." 03/01/2010 - "The p16INK4a biomarker was positive in 87.5% (21/24) of CIN II and 69% (18/26) of CIN I, while the HR HPV was positive in 75% (18/24) of CIN II and 50% (13/26) of CIN I. In ASCUS cytology, p16INK4a and HR HPV showed the same rate of positivity (28.5%; 2/7). " 05/01/2009 - "Among normal smears, only 12% (95% CI: 7-17%) were positive for the biomarker compared to 45% of ASCUS and LSIL (95% CI: 35-54% and 37-57%, respectively) and 89% of HSIL smears (95% CI: 84-95%). " 10/01/2008 - "ProEx C staining is a more sensitive and specific biomarker for detecting cervical disease than adjunct testing for hr-HPV status in Papanicolaou tests with ASC-US."
10.	Glucose (Dextrose)FDA LinkGeneric 07/01/1980 - "Inclusion of a meiotic inhibitor (glucose) in sporulation medium inhibited three- and four-spored ascus production but not two-spored ascus production. " 02/01/1995 - "Best results, yielding sporulation and four-spore ascus formation frequencies up to 97 and 60%, respectively, were obtained by collection of the cells in exponential phase from liquid presporulation medium with 10% glucose and transfer of them to sporulation medium with 0.5% potassium acetate at 22 degrees C. " 10/01/1985 - "Metschnikowia australis can be differentiated from other Metschnikowia species and varieties by its inability to form chlamydospores, the formation of two needle-shaped ascospores per ascus, lack of glucose fermentation, and lack of assimilation of both methyl-alpha-D-glucoside and glucono-delta-lactone. " 02/01/2009 - "The species is characterized by the fermentation of glucose and galactose, formation of one to four spheroidal to ellipsoidal ascospores with warty surfaces in each ascus, and assimilation of a few carbon and nitrogen compounds. " 02/01/2008 - "The species is characterized by forming one or two globose spores in each ascus, fermenting glucose and galactose and assimilating few carbon and nitrogen compounds. "

Therapies and Procedures

1.	Aftercare (After-Treatment) 12/01/2017 - "There was no significant difference in the time of initial identification of abnormal cytology after treatment between the worse than LSIL and the ASC-US groups (P=0.054). " 08/01/2017 - "Progression occured in 8% (N-10) of LSIL and 4% HSIL (N-5), persistence in 58% (N-72) and regression in 29,8% (N-37) in 124 women with ASCUS lesion after treatment and repeated PAP test. " 08/01/2016 - "Samples from 566 women with ASCUS and 411 women after treatment were routinely tested with HC2 and, thereafter, with cobas. " 01/01/2014 - "HPV testing was proven most useful for women over 30 years old, in cases in which cytology identified ASC-US and after treatment for CIN. " 01/01/2012 - "After treatment, the number of cases of ASC-US decreased from 50 to 11. "
2.	Therapeutics 01/01/2013 - "Patients with ASC-H or ASCUS with repeated abnormal smears underwent colposcopic biopsy and subsequent therapies. " 07/01/2004 - "The highest benefit is for those cases classified initially as ASCUS, in which the HPV results point out a more accurate diagnosis and guide subsequent adequate therapy. " 05/01/1999 - "Women older than 55 with ASCUS were three times more likely to be receiving hormonal replacement therapy than similar-aged women with normal cervicovaginal smears. " 09/01/2000 - "Nonpregnant women, 18+ years old, with ASCUS or LSIL, no prior hysterectomy or ablative therapy to the cervix, were referred to one of four clinical centers around the United States. " 02/01/2001 - "In the ASCUS type a), Pap-test should be immediately repeated (processing defects) or after therapy (excessive inflammation). "
3.	Curettage 08/01/2007 - "To estimate the diagnostic yield of endocervical curettage (ECC) when performed as part of a colposcopic procedure in the multicenter ASCUS-LSIL Triage Study (ALTS), a randomized trial of management strategies for women with equivocal or mildly abnormal cytology. " 06/01/1996 - "All patients were identified for the study who had a coloposcopically obtained cervical biopsy specimen or endocervical curettage specimen recorded in the surgical pathology files at Beth Israel Hospital, Boston, Massachusetts, from April 1994 through September 1994 and had either prior or concurrent Pap smear(s) reported as ASCUS, ASCUS-favor reactive, ASCUS-favor SIL, or SIL-low grade (SIL-LG). " 11/01/1995 - "During this period 114 (0.7%) of 17,330 smears were diagnosed as ASCUS, 62 of which resulted in either follow-up cervical biopsies and/or endocervical curettages (61%) or repeat smears (39%), and form the basis of this study. " 01/01/2019 - "Women with ASCUS cytology underwent punch biopsy under colposcopy/endocervical curettage. " 02/01/2016 - "Subsequent endocervical curettage showed a small focus of immature, atypical squamous cells with abnormally positive p16 staining and an abnormally increased proliferative index staining pattern (evaluated with Ki-67) (Images 1A-1C). "
4.	Colposcopes 09/06/2018 - "Women with ASC-US and complete recall information of colposcope were selected as the study objects. " 01/01/2012 - "Meta-analytically cut-point analysis showed that using a cut-point of ASCUS the sensitivity in both settings is similar while anal cytology is less specific than cervical cytology (specificity [95% confidence interval] 0.33 [0.20-0.49] vs. 0.53[0.40-0.66], p = 0.04) for the detection of HSIL histopathology by colposcope directed punch biopsy. " 08/01/2008 - "Human papillomavirus test,colposcope and cervical biopsy were performed in 184 patients with a referral diagnosis of ASCUS by cervical cytology. " 07/25/2019 - "Colposcope biopsies were performed on women who were positive of HPV 16, 18, and positive of HPV types other than 16,18 with cytology [≥ atypical squamous cell of undetermined signification (ASCUS)], or HPV negative but abnormal of cytology [≥ low grade squamous intraepithelial lesion (LSIL)]. " 02/01/2010 - "Biopsy under colposcope was performed in women who were HPV-positive with LCT >or= atypical squamous cells of undetermined sign (ASCUS) or HPV-negative with LCT >or= low grade squamous intraepithelial lesion (LSIL), with the pathological results as the golden standards. "
5.	Conservative Treatment 06/01/1996 - "A conservative management seems appropriate for patients with ASCUS and ASCUS-favor reactive." 11/01/2001 - "A recently published study of the management of low-grade cytologic smears compared immediate colposcopy to human papillomavirus (HPV) triage and entry cytology smears (conservative management) as three triage techniques for managing atypical squamous cells of undetermined significance (ASCUS) smears (Atypical Squamous Cells of Undetermined Significance/Low-grade Squamous Intraepithelial Lesion Triage Study [ALTS]). " 06/01/2012 - "To investigate whether the 2006 American Society for Colposcopy and Cervical Pathology guidelines for conservative management of minimally abnormal Pap test results (atypical squamous cells of undetermined significance, human papillomavirus-positive, and low-grade squamous intraepithelial lesions) and moderate dysplasia (cervical intraepithelial neoplasia 2) in adolescents 1) resulted in fewer colposcopies and loop electrosurgical excision procedures (LEEPs) in adolescents or 2) resulted in unintended treatment changes in older age groups. " 01/18/2006 - "The model compared the incremental costs per case of CIN3+ detected as measured by the incremental cost-effectiveness ratio (ICER) for the following management strategies for women with ASCUS: immediate colposcopy, HPV DNA testing, and conservative management with up to three cytology examinations. " 06/01/2003 - "A total of 3488 women with a community-based ASCUS interpretation were randomly assigned to immediate colposcopy, triage that was based on enrollment HPV DNA testing and liquid-based cytology at a colposcopy referral threshold of high-grade squamous intraepithelial lesion (HSIL), or conservative management based on repeat cytology at a referral threshold of HSIL. "