Primary prevention through the use of human papillomavirus (HPV) vaccination is expected to impact both cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS). While CIN is well described, less is known about the epidemiology of AIS, a rare cervical precancer. We identified AIS and CIN grade 3 (CIN3) cases through population-based surveillance, and analyzed data on HPV types and incidence trends overall, and among women screened for cervical cancer. From 2008 to 2015, 470 AIS and 6,587 CIN3 cases were identified. The median age of women with AIS was older than those with CIN3 (35 vs. 31 years; p < 0.01). HPV16 was the most frequently detected type in both AIS and CIN3 (57% in AIS; 58% in CIN3), whereas HPV18 was the second most common type in AIS and less common in CIN3 (38% vs. 5%; p < 0.01). AIS lesions were more likely than CIN3 lesions to be positive for high-risk types targeted by the bivalent and quadrivalent vaccines (HPV16/18, 92% vs. 63%; p < 0.01), and 9-valent vaccine (HPV16/18/31/33/45/52/58, 95% vs. 87%; p < 0.01). AIS incidence rates decreased significantly in the 21-24 year age group (annual percent change [APC] overall: -22.1%, 95% CI: -33.9 to -8.2; APC among screened: -16.1%, 95% CI: -28.8 to -1.2), but did not decrease significantly in any older age group. This report on the largest number of genotyped AIS cases to date suggests an important opportunity for vaccine prevention of AIS, and is the first to document a decline in AIS incidence rates among young women during the vaccine era.© 2019 UICC.

While the incidence of squamous carcinoma of the cervix has declined in countries with organised screening, adenocarcinoma has become more common. Cervical screening by cytology often fails to prevent adenocarcinoma. Using prospectively recorded cervical screening data in England and Wales, we conducted a population-based case-control study to examine whether cervical screening leads to early diagnosis and down-staging of adenocarcinoma. Conditional logistic regression modelling was carried out to provide odds ratios (ORs) and 95% confidence intervals (CIs) on 12,418 women with cervical cancer diagnosed between ages 30 and 69 and 24,453 age-matched controls. Of women with adenocarcinoma of the cervix, 44.3% were up to date with screening and 14.6% were non-attenders. The overall OR comparing women up to date with screening with non-attenders was 0.46 (95% CI: 0.39-0.55) for adenocarcinoma. The odds were significantly decreased (OR: 0.22, 95% CI: 0.15-0.33) in up to date women with Stage 2 or worse adenocarcinoma, but not for women with Stage1A adenocarcinoma 0.71 (95% CI: 0.46-1.09). The odds of Stage 1A adenocarcinoma was double among lapsed attenders (OR: 2.35, 95% CI: 1.52-3.62) compared to non-attenders. Relative to women with no negative cytology within 7 years of diagnosis, women with Stage1A adenocarcinoma were very unlikely to be detected within 3 years of a negative cytology test (OR: 0.08, 95% CI: 0.05-0.13); however, the odds doubled 3-5 years after a negative test (OR: 2.30, 95% CI: 1.67-3.18). ORs associated with up to date screening were smaller for squamous and adenosquamous cervical carcinoma. Although cytology screening is inefficient at preventing adenocarcinomas, invasive adenocarcinomas are detected earlier than they would be in the absence of screening, substantially preventing Stage 2 and worse adenocarcinomas.© 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

We aimed to determine the frequency of human papillomavirus-independent (HPVI) cervical squamous cell carcinoma (SCC) and to describe clinicopathologic characteristics. Among 670 patients with surgically treated SCCs in an established multi-institutional cohort, 447 had available tissue. Tissue microarrays were constructed and studied by in situ hybridization (ISH) for high-risk and low-risk human papillomavirus (HPV) mRNA and immunohistochemistry for p16 and p53. Tumors were HPVI if negative by HPV ISH and they failed to show diffuse p16 positivity by immunohistochemistry, and human papillomavirus-associated (HPVA) if positive by HPV ISH. Ten HPVI SCCs and 435 HPVA SCCs were identified; 2 cases were equivocal and excluded from analysis. The overall rate of HPVI SCC was low (2%) but was higher among older patients (7% in patients above 60 y of age and 17% in patients above 70 y of age). Compared with HPVA, patients with HPVI SCC were significantly older (median age, 72 vs. 49, P <0.001) and diagnosed at a higher stage (40% vs. 18% with stage III/IV disease, P =0.055). p53 expression was varied; 2 cases (20%) had null expression and 8 (80%) had wild-type expression. HPVI SCCs were heterogenous, with keratinizing, nonkeratinizing, and warty morphologies observed. Several cases had a precursor lesion reminiscent of differentiated vulvar intraepithelial neoplasia, with prominent basal atypia and hypereosinophilia or a basaloid-like morphology. Two patients (20%) had distant recurrences within 12 months, and 3 (30%) died of disease during follow-up. HPVI SCCs are rare tumors that are more common among older patients with higher stage disease and have important clinical and histologic differences from HPVA SCCs.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

We assessed the age-related prevalence of high risk human papillomavirus (HR-HPV) genotypes and the genotype-associated risk for high-grade cervical intraepithelial neoplasia (CIN) in a large U.S. screening population.A total of 40,901 women aged ≥25 years were screened with liquid-based cytology and HPV testing in the ATHENA (Addressing the Need for Advanced HPV Diagnostics) trial. Genotyping was performed using the LINEAR ARRAY HPV Genotyping Test.HPV16 was the most prevalent genotype in all age groups, ranging from 3.5% to 0.8% in women aged 25-29 and ≥50 years, respectively. The next most prevalent genotypes were HPV52, HPV31 and HPV18. In the overall population, HPV16 conferred the greatest absolute risk of ≥CIN3 both in women aged 25-29 and ≥30 years (14.2% and 15.1%, respectively) followed by HPV31 (8.0% and 7.9%), HPV52 (6.7% and 4.4%) and HPV18 (2.7% and 9.0%). Similar trends were seen in women with negative cytology. The percent positivity increased markedly with disease progression for HPV16 and HPV18 which were responsible for 45.6% and 8.4% of ≥CIN3, respectively. Of note, HPV 18 was responsible for 50% of adenocarcinoma in situ (AIS) and 50% of invasive cancer cases.HPV16 played a major role in the development of ≥CIN3 irrespective of age, supporting the identification of HPV16 in primary screening for all women. Identification of HPV18 is also warranted, given its significant contribution to AIS and cancer. Identification of non-16/18 genotypes as a pool should provide sufficient information for screening.Copyright © 2015. Published by Elsevier Inc.

This publication represents an extensive literature review with the goal of providing guidelines for the evaluation and management of cervical adenocarcinoma in situ (AIS). The authors drafted the guidelines on behalf of the Society of Gynecologic Oncology, and the guidelines have been reviewed and endorsed by the ASCCP. These guidelines harmonize with the ASCCP Risk-Based Management Consensus Guidelines and provide more specific guidance beyond that provided by the ASCCP guidelines. Examples of updates include recommendations to optimize the diagnostic excisional specimen, AIS management in the setting of positive compared with negative margins on the excisional specimen, surveillance and definitive management after fertility-sparing treatment, and management of AIS in pregnancy. The increasing incidence of AIS, its association with human papillomavirus-18 infection, challenges in diagnosis owing to frequent origin within the endocervical canal, and the possibility of skip lesions all make AIS a unique diagnosis whose management needs to be differentiated from the management of the more prevalent squamous cell dysplasia.

To determine the role of cervical cytology and colposcopy in the management of endocervical neoplasia.Colposcopy unit and cytology laboratory in a teaching hospital.Group 1 included 184 smears showing endocervical glandular neoplasia from 129 patients and group 2 included 101 patients with histology showing endocervical abnormalities in a 6-year period (1993-1998). Follow-up of 6-11 years to 2004 was available.Group 1 were identified from the cytology computer records. Group 2 were identified from histology records on the cytology database and a record of histology cases kept for audit purposes. The clinical records were examined retrospectively.The positive predictive value (PPV) of abnormal endocervical cells in smears was 81.1% for significant glandular/squamous [cervical glandular intraepithelial neoplasia (CGIN)/cervical intraepithelial neoplasia grade2 (CIN2 or worse)] lesions. The PPV of colposcopy was 93.5% for significant glandular/squamous lesions of the cervix. The postcolposcopy probability of a significant lesion when colposcopy was normal was 87.5%. The sensitivity of colposcopy in detecting endocervical lesions was 9.8%. The sensitivity of cervical smears in detecting a significant endocervical abnormality (CGIN or worse) was 66.3%. The false negative rate for cytology of endocervical glandular lesions was 4.0%.Endocervical glandular neoplasia detected on cytology is predictive of significant cervical pathology even when colposcopy is normal, which supports excisional biopsy in the primary assessment of these smears. The high concomitant squamous abnormality rate justifies the use of colposcopy to direct biopsies from the ectocervix. Cervical cytology is the only current screening method for cervical glandular abnormalities but sensitivity is poor.

New colposcopy terminology was prepared by the Nomenclature Committee of the International Federation of Cervical Pathology and Colposcopy after a critical review of previous terminologies, online discussions, and discussion with national colposcopy societies and individual colposcopists. This document has been expanded to include terminology of both the cervix and vagina. The popular terms "satisfactory colposcopy" and "unsatisfactory colposcopy" have been replaced. The colposcopic examination should be assessed for three variables: 1) adequate or inadequate, with the reason given; 2) squamocolumnar junction visibility; and 3) transformation zone type. Other additions were the localization of the lesion to either inside or outside the transformation zone and determinants of size as well as location of cervical lesions. Two new signs were included in the terminology-the "inner border sign" and "ridge sign." The following definitions have been added: congenital transformation zone, polyp (ectocervical or endocervical), stenosis, congenital anomaly, and posttreatment consequence. In addition, the terminology includes standardization of cervical excision treatment types and cervical excision specimen dimensions. The International Federation of Cervical Pathology and Colposcopy recommends that the 2011 terminology replace all others and be implemented for diagnosis, treatment, and research.

The present study assessed (i) the clinical outcome of patients with conservatively treated cervical adenocarcinoma in situ (AIS), (ii) the accuracy of diagnosing AIS by cytology, colposcopy and histology, as well as (iii) the performance of cervical cytology and HPV testing in detection of residual or recurrent disease after conservatively treated AIS.A series of 42 consecutive women (mean age 40.5 years; range 27-63 years) underwent conservative (cone) treatment of AIS and were prospectively followed up for a mean of 40 months (median 42 months), using colposcopy, PAP smear, biopsy and HPV testing (with hybrid capture II) repeated at 6-month intervals.In their referral PAP test, only 42.9% of patients had atypical glandular cells (AGC) smear. Colposcopy was unsatisfactory in 54.8% cases and negative in 16.7%. Twenty four patients (57.1%) had AIS as a pure lesions and 18 combined with squamous cell lesion (four had invasive SCC). Persistent or recurrent disease was observed in 17 (40.4%) cases, 19% in patients with free margins, and 65% among those with involved margins on the first conization. In four patients, an adenocarcinoma (AdCa) stage IA1 was diagnosed during the follow-up. HPV testing significantly predicted disease persistence/clearance with OR 12.6 (95% CI 1.18-133.89), while the predictive power of PAP smear did not reach statistical significance at any of the follow-up visits. The combination of PAP smear and HPV testing gives SE of 90.0%, SP 50.0%, PPV 52.9% and NPV 88.9% at first follow-up, and 100% SE and 100% NPV at the second follow-up visit.These results suggest that HR-HPV test in conjunction with cytology offers clear advantages over single cytology in monitoring the women conservatively treated for cervical AIS.

The aim of this study was to evaluate the efficacy and safety of combination laser conization alone as definitive treatment of adenocarcinoma in situ (AIS) and to evaluate the safety of a conservative expectant strategy irrespective of cone margin status.Sixty consecutive patients with histologically proven adenocarcinoma in situ were treated with combination laser conization from 1990 to April 2001. In 58 cases this was considered final therapy, and patients were followed for a mean period of 49 months.The mean age was 34.9 years. Preconization evaluation demonstrated AIS in 76.7%. In 58 cases conization was considered final therapy, and in these cone margins were involved in 15 cases. Twenty-seven patients (46.6%) were followed for more than 60 months. Totally, 4 recurrences (6.9%) were observed. One recurrence was observed in patients with involved margins (6.7%) 4 months after conization, and 3 recurrences in patients with uninvolved margins (6.9%) were registered, in 2 cases more than 5 years after conization. No case of invasive disease was diagnosed during follow-up. The mean cone height was 19 mm; 16.7% of the cone biopsies were more than 25 mm.Combination laser conization was an effective treatment of AIS, and an expectant follow-up schedule based on cytology was demonstrated to be safe irrespective of cone margin status after a significant follow-up period. A potential risk of overtreatment and unnecessary worrying of the patients exists if further treatment is based solely on the status of the cone margins. Only prospective studies of similar strategies will give sufficient evidence for valid recommendations concerning the management of AIS.

To evaluate prevalence and diagnostic performance of three colposcopic images to diagnose squamous and glandular cervical precursor neoplasias.

To determine the clinical outcomes of women with "?glandular neoplasia of endocervical type" on cervical cytology, and to review all diagnoses of cervical adenocarcinoma in situ over a 5 year period at our institution.Retrospective case-note review of all women referred to colposcopy with "?Glandular neoplasia of endocervical type" on cervical cytology and all women diagnosed with cervical adenocarcinoma in situ after biopsy or excision, from January 2014 until December 2018 in a London district hospital.From 55 women who were referred with "?Glandular neoplasia of endocervical type", 47 (85.4%) had a significant pathology on histopathological analysis: adenocarcinoma in situ (n=22); invasive cancer (n=7); high-grade CIN (n=18). Women with a history of a borderline abnormality on cervical cytology within the last five years were significantly more likely to be diagnosed with adenocarcinoma in situ or invasive cancer (P<0.05). For the same period 49 women had histologically proven Adenocarcinoma in situ. From them 22 (44.8%) were referred as possible Cervical Glandular Intraepithelial Neoplasia. Regarding the women referred to colposcopy for other reasons, the indications were the following: borderline dyskaryosis (n=13); high-grade dyskaryosis (n=8); low-grade dyskaryosis (n=4); postcoital bleeding (n=2).Due to the raised risk of significant gynaecological pathology in women with "?Glandular neoplasia of endocervical type" on cervical cytology, excisional biopsy is essential. Colposcopic impression varies significantly and complete excision of the abnormal lesions should be achieved. Adenocarcinoma in situ is a histological diagnosis and should always be considered during colposcopical and cytopathological assessment.This article is protected by copyright. All rights reserved.

Colposcopic features of cervical adenocarcinoma in situ (AIS) and adenocarcinoma exist, and colposcopists can learn to recognize them. This ability will increase the colposcopic discovery rate for these lesions and can lead to appropriate management in early stages. An excisional biopsy with negative margins is required to differentiate between in situ and invasive disease. The general categories of revealing features are surface patterns and blood vessels. Surface patterns indicative of AIS and adenocarcinoma are (1) lesions overlying columnar epithelium not contiguous with the squamocolumnar border; (2) lesions with large "gland"/cleft openings; (3) papillary lesions; (4) lesion exhibiting epithelial budding; and (5) variegated red and white lesions. Blood vessels indicative of AIS or adenocarcinoma are (1) waste-thread-like vessels; (2) tendril-like vessels; (3) rootlike vessels; (4) character-writing-like vessels; and (5) single and multiple dotlike formations in tips of papillary excrescences. Some of these characteristics also are apparent when other disease processes are present, but an observant colposcopist can differentiate lesions using inclusionary and exclusionary criteria.

To evaluate the diagnostic accuracy of the 2011 International Federation for Cervical Pathology and Colposcopy (IFCPC) colposcopic terminology.The clinicopathological data of 2262 patients who underwent colposcopy from September 2012 to September 2016 were reviewed. The colposcopic findings, colposcopic impression, and cervical histopathology of the patients were analyzed. Correlations between variables were evaluated using cervical histopathology as the gold standard.Colposcopic diagnosis matched biopsy histopathology in 1482 patients (65.5%), and the weighted kappa strength of agreement was 0.480 (P<0.01). Colposcopic diagnoses more often underestimated (22.1%) than overestimated (12.3%) cervical pathology. There was no significant difference between the colposcopic diagnosis and cervical pathology agreement among the various grades of lesions (P=0.282). The sensitivity, specificity for detecting high-grade lesions/carcinoma was 71.6% and 98.0%, respectively. Multivariate analysis showed that major changes were independent factors in predicting high-grade lesion/carcinoma, whereas transformation zone, lesion size, and non-stained were not statistically related to high-grade lesion/carcinoma.The 2011 IFCPC terminology can improve the diagnostic accuracy for all lesion severities. The categorization of major changes and minor changes is appropriate. However, colposcopic diagnosis remains unsatisfactory. Poor reproducibility of type 2 transformation zone and the significance of leukoplakia require further study.

The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of and approach to colposcopy for cervical cancer prevention in the United States.The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. This article describes the rationale, evidence, and recommendations related to risk-based colposcopy practice.Women referred to colposcopy have a wide range of underlying precancer risk, which can be estimated by referral screening tests including cytology and human papillomavirus testing, in conjunction with the colposcopic impression. Multiple targeted biopsies, at least 2 and up to 4, are recommended to improve detection of prevalent precancers. At the lowest end of the risk spectrum, untargeted biopsies are not recommended, and women with a completely normal colposcopic impression can be observed. At the highest end of the risk spectrum, immediate treatment is an alternative to biopsy confirmation.Assessing the risk of cervical precancer at the colposcopy visit allows for modification of colposcopy procedures consistent with a woman's risk. Implementation of these recommendations is expected to lead to improved detection of cervical precancers at colposcopy, while providing more reassurance of negative colposcopy results.

The most recent guidelines for colposcopy practice in the United States, the 2017 Colposcopy Standards Consensus Guidelines, did not include recommendations for endocervical curettage (ECC). This document provides updated guidelines for use of ECC among patients referred for colposcopy.Consensus guidelines for the use of ECC were developed in 2012. To update these guidelines in concordance with the 2017 Colposcopy Standards process, an expert workgroup was convened in 2021. Literature had been previously reviewed through 2011, before the 2012 guideline. Literature from the years 2012-2021 and data from the NCI Biopsy study were reviewed, focusing on the additional yield of ECC.Endocervical curettage is recommended for patients with high-grade cytology, human papillomavirus 16/18 infection, positive results on dual staining for p16/Ki67, for those previously treated for known or suspected cervical precancer or considering observation of cervical intraepithelial neoplasia grade 2, and when the squamocolumnar junction is not fully visualized at colposcopy. Endocervical curettage is preferred for all patients aged older than 40 years. Endocervical curettage is acceptable for all nonpregnant patients undergoing colposcopy but may be omitted when a subsequent excisional procedure is planned, the endocervical canal does not admit a sampling device, or in nulliparous patients aged younger than 30 years, with cytology reported as atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion regardless of whether the squamocolumnar junction is fully visualized. Endocervical curettage is unacceptable in pregnancy.These guidelines for ECC add to the 2017 consensus recommendations for colposcopy practice in the United States.Copyright © 2022 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a "work of the United States Government" for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.