American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer.

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.

A common clinical dilemma: Management of abnormal vaginal cytology and human papillomavirus test results.

OBJECTIVE: Vaginal cancer is an uncommon cancer of the lower genital tract, and standardized screening is not recommended. Risk factors for vaginal cancer include a history of other lower genital tract neoplasia or cancer, smoking, immunosuppression, and exposure to diethylstilbestrol in utero. Although cervical cancer screening after total hysterectomy for benign disease is not recommended, many women inappropriately undergo vaginal cytology and/or human papillomavirus (hrHPV) tests, and clinicians are faced with managing their abnormal results. Our objective is to review the literature on vaginal cytology and hrHPV testing and to develop guidance for the management of abnormal vaginal screening tests. METHODS: An electronic search of the PubMed database through 2015 was performed. Articles describing vaginal cytology or vaginal hrHPV testing were reviewed, and diagnostic accuracy of these tests when available was noted. RESULTS: The available literature was too limited to develop evidence-based recommendations for managing abnormal vaginal cytology and hrHPV screening tests. However, the data did show that 1) the risk of vaginal cancer in women after hysterectomy is extremely low, justifying the recommendation against routine screening, and 2) in women for whom surveillance is recommended, e.g. women post-treatment for cervical precancer or cancer, hrHPV testing may be useful in identification of vaginal cancer precursors. CONCLUSION: Vaginal cancer is rare, and asymptomatic low-risk women should not be screened. An algorithm based on expert opinion is proposed for managing women with abnormal vaginal test results.

A Common Clinical Dilemma: Management of Abnormal Vaginal Cytology and Human Papillomavirus Test Results.

OBJECTIVE: Vaginal cancer is an uncommon cancer of the lower genital tract, and standardized screening is not recommended. Risk factors for vaginal cancer include a history of other lower genital tract neoplasia or cancer, smoking, immunosuppression, and exposure to diethylstilbestrol in utero. Although cervical cancer screening after total hysterectomy for benign disease is not recommended, many women inappropriately undergo vaginal cytology and/or human papillomavirus (HPV) tests, and clinicians are faced with managing their abnormal results. Our objectives were to review the literature on vaginal cytology and high-risk HPV (hrHPV) testing and to develop guidance for the management of abnormal vaginal screening tests. MATERIALS AND METHODS: An electronic search of the PubMed database through 2015 was performed. Articles describing vaginal cytology or vaginal hrHPV testing were reviewed, and diagnostic accuracy of these tests when available was noted. RESULTS: The available literature was too limited to develop evidence-based recommendations for managing abnormal vaginal cytology and hrHPV screening tests. However, the data did show that (1) the risk of vaginal cancer in women after hysterectomy is extremely low, justifying the recommendation against routine screening, and (2) in women for whom surveillance is recommended, e.g., women posttreatment for cervical precancer or cancer, hrHPV testing may be useful in identification of vaginal cancer precursors. CONCLUSIONS: Vaginal cancer is rare, and asymptomatic low-risk women should not be screened. An algorithm based on expert opinion is proposed for managing women with abnormal vaginal test results.

Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology and cotesting (cytology in combination with hrHPV testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective US-based registration study. Thirteen experts including representatives from the Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the FDA for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for healthcare providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk HPV (hrHPV) testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective US-based registration study. Thirteen experts including representatives from the Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the FDA for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

2013 Vulvodynia Guideline update.

Vulvodynia is a complex disorder that can be difficult to treat. Most patients describe it as burning, stinging, irritation, or rawness. Vulvodynia is a costly disease both economically and on its negative impact on patient quality of life. Although many treatment options are available, no one treatment is effective for all patients, thus the need to individualize management. Measures such as gentle vulvar care, medication, biofeedback training, physical therapy, sexual counseling and surgery, as well as complementary and alternative therapies are available to treat the condition with varying success.

2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors.

A group of 47 experts representing 23 professional societies, national and international health organizations, and federal agencies met in Bethesda, MD, September 14-15, 2012, to revise the 2006 American Society for Colposcopy and Cervical Pathology Consensus Guidelines. The group's goal was to provide revised evidence-based consensus guidelines for managing women with abnormal cervical cancer screening tests, cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS) following adoption of cervical cancer screening guidelines incorporating longer screening intervals and co-testing. In addition to literature review, data from almost 1.4 million women in the Kaiser Permanente Northern California Medical Care Plan provided evidence on risk after abnormal tests. Where data were available, guidelines prescribed similar management for women with similar risks for CIN 3, AIS, and cancer. Most prior guidelines were reaffirmed. Examples of updates include: Human papillomavirus-negative atypical squamous cells of undetermined significance results are followed with co-testing at 3 years before return to routine screening and are not sufficient for exiting women from screening at age 65 years; women aged 21-24 years need less invasive management, especially for minor abnormalities; postcolposcopy management strategies incorporate co-testing; endocervical sampling reported as CIN 1 should be managed as CIN 1; unsatisfactory cytology should be repeated in most circumstances, even when HPV results from co-testing are known, while most cases of negative cytology with absent or insufficient endocervical cells or transformation zone component can be managed without intensive follow-up.

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer.

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 six working groups, and a recent symposium co-sponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), 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 (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16/18 infections.

Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP).

These recommendations represent the first statement by the Advisory Committee on Immunization Practices (ACIP) on the use of a quadrivalent human papillomavirus (HPV) vaccine licensed by the U.S. Food and Drug Administration on June 8, 2006. This report summarizes the epidemiology of HPV and associated diseases, describes the licensed HPV vaccine, and provides recommendations for its use for vaccination among females aged 9-26 years in the United States. Genital HPV is the most common sexually transmitted infection in the United States; an estimated 6.2 million persons are newly infected every year. Although the majority of infections cause no clinical symptoms and are self-limited, persistent infection with oncogenic types can cause cervical cancer in women. HPV infection also is the cause of genital warts and is associated with other anogenital cancers. Cervical cancer rates have decreased in the United States because of widespread use of Papanicolaou testing, which can detect precancerous lesions of the cervix before they develop into cancer; nevertheless, during 2007, an estimated 11,100 new cases will be diagnosed and approximately 3,700 women will die from cervical cancer. In certain countries where cervical cancer screening is not routine, cervical cancer is a common cancer in women. The licensed HPV vaccine is composed of the HPV L1 protein, the major capsid protein of HPV. Expression of the L1 protein in yeast using recombinant DNA technology produces noninfectious virus-like particles (VLP) that resemble HPV virions. The quadrivalent HPV vaccine is a mixture of four HPV type-specific VLPs prepared from the L1 proteins of HPV 6, 11, 16, and 18 combined with an aluminum adjuvant. Clinical trials indicate that the vaccine has high efficacy in preventing persistent HPV infection, cervical cancer precursor lesions, vaginal and vulvar cancer precursor lesions, and genital warts caused by HPV types 6, 11, 16, or 18 among females who have not already been infected with the respective HPV type. No evidence exists of protection against disease caused by HPV types with which females are infected at the time of vaccination. However, females infected with one or more vaccine HPV types before vaccination would be protected against disease caused by the other vaccine HPV types. The vaccine is administered by intramuscular injection, and the recommended schedule is a 3-dose series with the second and third doses administered 2 and 6 months after the first dose. The recommended age for vaccination of females is 11-12 years. Vaccine can be administered as young as age 9 years. Catch-up vaccination is recommended for females aged 13--26 years who have not been previously vaccinated. Vaccination is not a substitute for routine cervical cancer screening, and vaccinated females should have cervical cancer screening as recommended.

Assessment of follow-up for low-grade cytological abnormalities in the National Breast and Cervical Cancer Early Detection Program, 2000-2005.

OBJECTIVE: To assess the management of women in the National Breast and Cervical Cancer Early Detection Program with low-grade squamous intraepithelial lesions (LSIL) before and after the American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines for management of abnormal cytology were published in 2002. MATERIALS AND METHODS: We examined the follow-up for 22,342 women with LSIL during 2 periods: 2000-2002 and 2003-2005. RESULTS: The percentage of providers who followed the recommended guidelines with colposcopy for an LSIL Pap test result increased by 9% from the pre-ASCCP to the post-ASCCP period. An increase was seen in every age and racial/ethnic group. Younger women (<30 years) and white women were more likely than comparison groups to be followed by colposcopy rather than a repeat Pap test. CONCLUSIONS: The increase in percentage of women having colposcopy in 2003, 1 year after the new guidelines were published, suggests a change in provider practices consistent with those guidelines.

Risk of cervical cancer associated with extending the interval between cervical-cancer screenings.

BACKGROUND: Although contemporary guidelines suggest that the intervals between Papanicolaou tests can be extended to three years among low-risk women with previous negative tests, the excess risk of cervical cancer associated with less frequent than annual screening is uncertain. METHODS: We determined the prevalence of biopsy-proven cervical neoplasia among 938,576 women younger than 65 years of age, stratified according to the number of previous consecutive negative Papanicolaou tests. Using a Markov model that estimates the rate at which dysplasia will progress to cancer, we estimated the risk of cancer within three years after one or more negative Papanicolaou tests, as well as the number of additional Papanicolaou tests and colposcopic examinations that would be required to avert one case of cancer given a particular interval between screenings. RESULTS: Among 31,728 women 30 to 64 years of age who had had three or more consecutive negative tests, the prevalence of biopsy-proven cervical intraepithelial neoplasia of grade 2 was 0.028 percent and the prevalence of grade 3 neoplasia was 0.019 percent; none of the women had invasive cervical cancer. According to our model, the estimated risk of cancer with annual Papanicolaou tests for three years was 2 in 100,000 among women 30 to 44 years of age, 1 in 100,000 among women 45 to 59 years of age, and 1 in 100,000 among women 60 to 64 years of age; these risks would be 5 in 100,000, 2 in 100,000, and 1 in 100,000, respectively, if screening were performed once three years after the last negative test. To avert one additional case of cancer by screening 100,000 women annually for three years rather than once three years after the last negative test, an average of 69,665 additional Papanicolaou tests and 3861 colposcopic examinations would be needed in women 30 to 44 years of age and an average of 209,324 additional Papanicolaou tests and 11,502 colposcopic examinations in women 45 to 59 years of age. CONCLUSIONS: As compared with annual screening for three years, screening performed once three years after the last negative test in women 30 to 64 years of age who have had three or more consecutive negative Papanicolaou tests is associated with an average excess risk of cervical cancer of approximately 3 in 100,000.

Cervical cancer incidence in a prevaccine era in the United States, 1998-2002.

OBJECTIVE: To report the incidence of cervical cancer by geography, race or ethnicity, and histology. METHODS: We examined combined data from the National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results Program covering 87% of the U.S. population. We calculated the age-adjusted incidence of cervical cancer by age, race or ethnicity, histology, and stage by region or state. RESULTS: Rates of invasive cancer per 100,000 females declined from 10.2 in 1998 to 8.5 in 2002. Incidence rates by state ranged from 6.6 to 12.3 per 100,000. Rates were especially high among Hispanic women aged 40 years or older (26.5 or more) and African-American women aged older than 50 years (23.5 or more). Rates of squamous cell carcinoma were significantly higher among African-American and Hispanic women than among their white counterparts. In contrast, rates of adenocarcinoma (18% of all cases) were significantly lower among African-American women than in white women (rate ratio 0.88, P<.05). Rates of adenocarcinoma were significantly higher among Hispanic women than among non-Hispanics (rate ratio 1.71, P<.05). Although no regional differences were noted for adenocarcinoma, rates of squamous cell carcinoma were higher in the South than in other regions. CONCLUSION: Despite intense screening in the past decade, higher rates of cervical cancer persist among women in the South and women who are African American or Hispanic. This information could guide more focused interventions to increase access to screening with cervical cytology as well as vaccination against human papillomavirus. LEVEL OF EVIDENCE: III.

Cost-effectiveness of extending cervical cancer screening intervals among women with prior normal pap tests.

OBJECTIVE: Annual cervical cancer screening in women with many prior normal Pap tests is common despite limited evidence on the cost-effectiveness of this strategy. We estimated the cost-effectiveness of screening women with 3 or more prior normal tests compared with screening those with no prior tests. METHODS: We used a validated cost-effectiveness model in conjunction with data on the prevalence of biopsy-proven cervical neoplasia in women enrolled in the Centers for Disease Control and Prevention National Breast and Cervical Cancer Early Detection Program. Women were grouped according to age at the final Program Pap test (aged < 30, 30-44, 45-59, and 60-65 years) and by screening history (0, 1, 2, and 3+ consecutive prior normal Program tests) to estimate cost per life-year and quality-adjusted life-year associated with annual, biennial, and triennial screening. RESULTS: For women aged 30-44 years with no prior tests, incremental cost-effectiveness ratios ranged from 20,533 US dollars for screening triennially (compared with no further screening) to 331,837 US dollars for screening annually (compared with biennially) per life-year saved. Among same-aged women with 3 or more prior normal Program tests, incremental cost-effectiveness ratios for the same measures ranged from 60,029 US dollars to 709,067 US dollars per life-year saved. Inclusion of the most conservative utility estimates resulted in incremental cost-effectiveness ratios in excess of 100,000 US dollars per quality-adjusted life-year saved associated with annual screening of same-aged women with 3 or more prior normal tests compared with biennial screening. CONCLUSION: As the number of prior normal Pap tests increases, the costs per life-year saved increase substantially. Resources should be prioritized for screening those never or rarely screened women. LEVEL OF EVIDENCE: II-2.

Adherence to guidelines for follow-up of low-grade cytologic abnormalities among medically underserved women.

OBJECTIVE: To determine whether women in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) who had findings on a Papanicolaou (Pap) test of atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL) were followed up in accordance with the interim guidelines for management of abnormal cervical cytology. METHODS: For this study period, the guidelines for a Pap result of ASC-US or LSIL specified follow-up by Pap tests repeated every 4 to 6 months for 2 years. If a second report of ASC-US or LSIL was made, the patient was to have colposcopy. We analyzed data from 10,004 women who had a result of ASC-US or LSIL followed by a second ASC-US or LSIL from 1991-2000. RESULTS: As judged by the guidelines, 44% of women who had 2 low-grade abnormalities were followed up appropriately with colposcopy. Among women with 2 ASC-US results, those aged less than 30 years were more likely to receive colposcopy than the other age groups, while women who were aged 60 years and older were more likely to be followed up with a third Pap test. For each of the 4 result groups, American Indian or Alaska Native women had the highest percentages of a third Pap test, whereas Black or African-American women had a higher percentage of no follow-up. CONCLUSION: More than one half of the women studied were not followed up in accordance with the established guidelines for managing abnormal cervical cytology. Factors such as age and race or ethnicity influence whether women with cytologic abnormalities receive appropriate follow-up.

Report from the CDC. Pap test intervals used by physicians serving low-income women through the National Breast and Cervical Cancer Early Detection Program.

The National Breast and Cervical Cancer Early Detection Program (NBCCEDP), administered by the Centers for Disease Control and Prevention (CDC), provides breast and cervical cancer screening to low-income women who are uninsured or underinsured. For women with three consecutive annual Pap tests with normal findings, the NBCCEDP supports extending the screening interval to every 3 years. Thirteen telephone focus groups were conducted with physician providers in 17 states and the District of Columbia to investigate familiarity with NBCCEDP's triennial Pap test policy, the Pap test intervals actually used, and the factors influencing screening interval selection. No participants were familiar with NBCCEDP's triennial Pap test policy, and none reported routinely extending the screening interval after three consecutive annual Pap tests with normal findings. Two patterns of screening interval use were reported: annual screeners continued performing yearly Pap tests, and selective extended screeners offered an extended interval to select patients. Annual and selective extended screeners reported that both unique and common factors influenced the screening intervals they used. The NBCCEDP has established its cancer screening priorities to focus limited resources on the goal of providing services to eligible women who have rarely or never been screened. Increased efforts are needed to educate physicians about the science supporting an extended Pap screening interval and overcome the barriers associated with its adoption.

Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk human papillomavirus [hrHPV] testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective U.S.-based registration study. Thirteen experts, including representatives from the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the U.S. Food and Drug Administration (FDA) for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

Cervical screening in the National Breast and Cervical Cancer Early Detection Program, 1995-2001.

OBJECTIVE: To describe results of cervical cytology screening among low-income and uninsured women in the National Breast and Cervical Cancer Early Detection Program. METHODS: We analyzed data from 750,591 women who received their first Papanicolaou (Pap) test in the program between July 1995 and March 2001. RESULTS: Nearly 85% of the women were aged 40 years or older. Almost half were members of racial or ethnic minority groups. Overall, the percentage of abnormal Pap test results decreased with increasing age. The rates of cervical intraepithelial neoplasia (CIN) were highest in the younger age groups but the rate of invasive cancer increased with age. White women had the highest age-adjusted percentage of abnormal Pap test results and the highest rate of biopsy-confirmed CIN 2 or worse. CONCLUSIONS: In this nationwide screening program, only 7% of all biopsy-confirmed high-grade cervical lesions (CIN 2 or worse) were invasive cancer. This underscores the success of Pap screening in identifying preinvasive disease and preventing cancer. LEVEL OF EVIDENCE: II-3