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An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections., (Copyright © 2012 American Cancer Society, Inc.)

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections.

Objective: To provide revised evidence-based consensus guidelines for managing women with abnormal cervical cancer screening test results., Participants: A group of 146 experts, including representatives from 29 professional organizations, federal agencies, and national and international health organizations, met in Bethesda, MD, September 18-19, 2006, to develop the guidelines. MAJOR CHANGES IN GUIDELINES: The core recommendations for managing women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions were changed minimally. Postcolposcopy management for women with these cytological abnormalities is now identical. Management recommendations for these conditions did change for "special populations," such as adolescents for whom a more conservative approach incorporating cytological follow-up for 2 years was approved. Core recommendations for managing women with high-grade squamous intraepithelial lesions and atypical glandular cells also underwent only minor modifications. More emphasis is placed on immediate "screen-and-treat" approaches when managing women with high-grade squamous intraepithelial lesion. Testing for high-risk human papillomavirus DNA is incorporated into the management of women with atypical glandular cells after their initial evaluation with colposcopy and endometrial sampling. The 2004 Interim Guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening in women 30 years and older was formally adopted with only very minor modifications., Conclusions: The 2006 Consensus Guidelines reflect recent data from large clinical trials and advances in technology and are designed to assist clinicians of all subspecialties.

A group of 146 experts representing 29 organizations and professional societies met Sept. 18-19, 2006, in Bethesda, MD, to develop revised evidence-based, consensus guidelines for managing women with abnormal cervical cancer screening tests. The management of low-grade cervical intraepithelial neoplasia (CIN) grade 1 has been modified significantly. Previously, management depended on whether colposcopy was satisfactory and treatment using ablative or excisional was acceptable for all women with CIN 1. In the new guidelines, cytological follow-up is the only recommended management option for women with CIN 1 who have low-grade referral cervical cytology, regardless of whether the colposcopic examination is satisfactory. Treatment is particularly discouraged in adolescents. The basic management of women in the general population with CIN 2,3 underwent only minor modifications, but options for the conservative management of adolescents with CIN 2,3 have been expanded. Moreover, management recommendations for women with biopsy-confirmed adenocarcinoma in situ are now included.

Objective: To provide updated consensus guidelines for the management of women with cervical intraepithelial neoplasia (CIN) or adenocarcinoma in situ (AIS)., Participants: A group of 146 experts including representatives from 29 professional organizations, federal agencies, and national and international health organizations met on September 18-19, 2006, in Bethesda, MD, to develop the guidelines. MAJOR CHANGES IN THE GUIDELINES: The management of women with CIN grade 1 (CIN 1) has been modified significantly. In the earlier guidelines, management depended on whether the colposcopic examination was satisfactory and treatment using ablative or excisional methods was acceptable for women with CIN 1. In the new guidelines, cytological follow-up is the only recommended management option, regardless of whether the colposcopic examination is satisfactory, for women with CIN 1 who have a low-grade referral cervical cytology. Treatment of CIN 1 is particularly discouraged in adolescents. The basic management of women in the general population with CIN 2,3 underwent only minor modifications, but options for the conservative management of adolescents with CIN 2,3 have been expanded. Moreover, management recommendations for women with biopsy-confirmed AIS are now included., Conclusion: Updated evidenced-based guidelines have been developed for the management of women with CIN or AIS. These guidelines reflect recent changes in our understanding of human papillomavirus-associated diseases of the cervix and the potential impact of treatment on future pregnancies.

A group of 146 experts representing 29 organizations and professional societies met September 18-19, 2006, in Bethesda, MD, to develop revised evidence-based, consensus guidelines for managing women with abnormal cervical cancer screening tests. Recommendations for managing atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion (LSIL) are essentially unchanged. Changes were made for managing these conditions in adolescents for whom cytological follow-up for 2 years was approved. Recommendations for managing high-grade squamous intraepithelial lesion (HSIL) and atypical glandular cells (AGC) also underwent only minor modifications. More emphasis is placed on immediate screen-and-treat approaches for HSIL. Human papillomavirus (HPV) testing is incorporated into the management of AGC after their initial evaluation with colposcopy and endometrial sampling. The 2004 Interim Guidance for HPV testing as an adjunct to cervical cytology for screening in women 30 years of age and older was formally adopted with only very minor modifications.

Objective: The Home Study Course is intended for the practicing colposcopist or practitioner who is seeking to develop or enhance his or her colposcopic skills. The goal of the course is to present colposcopic cases that are unusual or instructive in terms of appearance, presentation, or management, or that demonstrate new and important knowledge in the area of colposcopy or pathology. Participants may benefit from reading and studying the material or from testing their knowledge by answering the questions., Accme Accreditation: The American Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The American Society for Colposcopy and Cervical Pathology designates this educational activity for a maximum of 1 AMA PRA Categorys I Creditt. Physicians should only claim credit commensurate with the extent of their participation in the activity. ASCCP also designates their educational activity for 1 Category 1 credit hour of the ASCCP's Program for Continuing Professional Development. Credit is available for those who choose to apply. The Home Study Course is planned and produced in accordance with the ACCME's Essential Areas and Elements., Disclosures: The clinical history and images in the Home Study Course may represent an actual case, but not always. To improve educational quality, some gross, cytological, or histological images may come from photographic libraries. Good teaching cases are often difficult to obtain, and we encourage our readers to submit cases with high-quality images to the Home Study Course editor or executive editor to consider for publication. Lastly, faculty must disclose any significant financial interest or relationship with proprietary entities that may have a direct relationship to the subject matter. For this course, the authors had no such relationship to report.

Objective: The Home Study Course is intended for the practicing colposcopist or practitioner who is seeking to develop or enhance his or hercolposcopic skills. The goal of the course is to present colposcopic cases that are unusual or instructive in terms of appearance, presentation, or management or to present colposcopic cases that demonstrate new and important knowledge in the area of colposcopyor pathology. Participants may benefit from reading and studying the material or from testing their knowledge by answering the questions., Accme Accreditation: The American Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The ASCCP designates this continuing medicaleducation activity for 1 hour category 1 credit of the ASCCP's Program for Continuing Professional Development and the Physician's Recognition Award of the American Medical Association. Credit is available for those who choose to apply. The Home Study Course is planned and produced in accordance with the ACCME's Essential Areas and Elements., Disclosure: Faculty must disclose any significant financial interest or relationship with proprietary entities that may have a directrelationship to the subject matter. For this course, the author had no such relationship to report.

The American Society for Colposcopy and Cervical Pathology sponsored a consensus conference in 2001 to develop evidence-based guidelines for women with histologic abnormalities of the cervix. The options for management of cervical intraepithelial neoplasia 1, 2, and 3 are ranked according to the strength of the recommendation and the quality of the evidence. Follow-up with repeat cytology at six and 12 months or DNA testing for high-risk types of human papillomavirus at 12 months is the preferred management approach for women with cervical intraepithelial neoplasia 1 and satisfactory initial colposcopy. If results from repeat cytology are reported as atypical squamous cells of undetermined significance or greater, or if DNA human papillomavirus testing is positive for oncogenic types of the virus, repeat colposcopy is preferred. When the initial colposcopy is unsatisfactory, a diagnostic excisional procedure is preferred. Follow-up without treatment is acceptable only in women who are pregnant and adolescents with cervical intraepithelial neoplasia 1 who had unsatisfactory colposcopy. Biopsy-confirmed cervical intraepithelial neoplasia 2 and 3 requires treatment except during pregnancy and in compliant adolescents with cervical intraepithelial neoplasia 2 and negative endocervical curettage. When colposcopy is satisfactory, treatment includes ablative or excisional procedures. A diagnostic excisional procedure is recommended in women with biopsy-confirmed cervical intraepithelial neoplasia 2 or 3 and unsatisfactory colposcopy.

Objective: In postmenopausal women, differentiating high-grade cervical intraepithelial neoplasia (CIN 2,3) from atrophic uterine cervical squamous epithelium histologically may pose a diagnostic challenge. Recent studies have indicated the value of using a combination of Ki-67, cyclin E, and p16 immunohistochemical analysis in recognizing CIN 2,3. In this study, we compared the staining features of Ki-67, cyclin E, and p16 in cervix specimens from postmenopausal women to distinguish CIN 2,3 from atrophy., Methods: Twenty-six formalin-fixed paraffin-embedded archival cervical specimens (4 biopsy, 8 laser cone, and 14 total hysterectomy samples) were selected from 25 women 50 to 80 years of age (mean = 64 years). Cases included CIN 2,3 (n = 10), atrophy (n = 9), and coexistent CIN 2,3 and atrophy (n = 6). Slides were stained with monoclonal antibodies to Ki-67, cyclin E, and p16 using the avidin-biotin-peroxidase method. Strength of staining was graded as 1+ to 3+. Pattern of staining was described as diffuse, patchy, or scattered. Ki-67 staining restricted to the basal/parabasal zone was scored as negative., Results: All CIN 2,3 cases demonstrated variable positivity for Ki-67, cyclin E, and p16. Most CIN 2,3 cases showed strong p16 (81.3%) and Ki-67 (75.0%) reactivity, while only 31.3% of them showed strong cyclin E activity. Some CIN 2,3 cases demonstrated strong p16 but weak Ki-61 and cyclin E reactivity. All atrophic epithelia were negative for p16, cyclin E, and Ki-67. In coexistent CIN 2,3 and atrophy cases, the three-antibody panel clearly demarcated the transition from benign to neoplastic epithelia., Conclusion: P16 is the most valuable marker followed by Ki-67 for differentiating CIN 2,3. While cyclin E appears to add limited value on these two markers. Therefore, although the three-antibody immunohistochemical panel (p16, Ki-67, and cyclin E) can be a valuable adjunct to routine hematoxylin-eosin staining, it is also possible to use the two-antibody panel (p16 and Ki-67) to effectively distinguish CIN 2,3 from atrophy in postmenopausal women.

Objective: To explore the role played by excision of the transformation zone in women diagnosed with cervical intraepithelial neoplasia (CIN) in the disappearance of human papillomavirus (HPV)., Material and Methods: In a retrospective, cohort study, women with CIN who were treated by loop electrosurgical excision procedure of the transformation zone were compared with another group of women with CIN who were managed expectantly. The decision to treat or manage expectantly was made by one of the authors on clinical grounds. All patients were evaluated with cervical cytologic analysis, pathologic examination of excised tissue, and HPV DNA testing, which was considered positive when high-risk HPV types were detected. Among women treated with loop electrosurgical excision procedure, the median lag time was calculated from diagnosis of CIN to treatment. The median time for conversion from HPV-positive to HPV-negative status in both groups was compared, as well as the 1- and 2-year cure rates (defined as converting to HPV-negative status) in the treated and untreated groups., Results: In the treated group, 12% had CIN 1, 83% had CIN 2,3, 2% had cancer, and 3% had normal pathologic results. In the untreated group, 82% had CIN 1, 16% had CIN 2,3, and 2% had normal pathologic results (p < 0.0001). The lag time from the initial diagnosis of CIN to treatment was less than 1 month. The median follow-up time was 7 months (range, 1-121 months) in the treated group and 13 months (range, 1-70 months) in the untreated group. The 1-year rates of conversion to HPV-negative status, defined as the cure rates in the treated and untreated groups, were 65% (+/- 6%) and 23% (+/- 7%), respectively, and the 2-year cure rates in the treated and untreated groups were 90% (+/- 4%) and 56% (+/- 11%), respectively (p < 0.0001). Median time to conversion to a negative HPV status was 7.7 months for the treated patients compared with 19.4 months in the untreated patients (p < 0.0001)., Conclusions: Women treated by loop electrosurgical excision procedure are more likely convert to HPV-negative status at 1 and 2 years and do so significantly sooner than those managed expectantly.

Unlabelled: Human immunodeficiency virus (HIV) and human papillomavirus (HPV) are both sexually transmitted viruses with many risk factors in common. Studies have found that HIV-seropositive women are at least five times as likely to be infected with HPV as seronegative controls. In immunocompromised HIV-seropositive women, the risk of cervical intraepithelial neoplasia (CIN) is almost as high as in women with squamous intraepithelial lesions on their Pap smear. Some studies have shown the false-negative rate of cervical cytology in HIV-seropositive women to be very high, although others have shown it to be comparable with the rate in seronegative controls. However, given the prevalence of CIN in this population, even a "normal" false-negative rate may result in many missed CIN lesions. Among HIV-seropositive women and especially among those who are immunocompromised, CIN is more likely to progress and recur after treatment. Recurrence rates may reach 87 percent 36 months after treatment in markedly immunosuppressed women. Cryotherapy is especially ineffective in these patients. Vulvar condyloma and vulvar intraepithelial neoplasia (VIN) are much more prevalent in HIV-seropositive women and especially in those who are markedly immunosuppressed or who have been immunosuppressed for a prolonged period of time. It is recommended that all HIV-seropositive women undergo periodic evaluation at intervals no less than every 6 months. Immunocompromised women should be followed with cytology and colposcopy of the cervix and vulva, although those with normal immune systems may be followed with cytology alone. Because the rates of recurrence and progression are so high after treatment of these women, they should be followed with colposcopy and cytology every 6 months. New approaches to treatment need to be explored in this population., Target Audience: Obstetricians & Gynecologists, Family Physicians., Learning Objectives: After completion of this article, the reader will understand the association between the immune suppression of HIV and HPV-related diseases, be familiar with the treatment options for the HIV-seropositive woman with cervical intraepithelial neoplasia (CIN), understand the natural history of CIN in the patient with HIV-seropositivity, and become aware of the appropriate surveillance of the HIV-seropositive woman treated for CIN.