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This is the fourth American Society of Colposcopy and Cervical Pathology (ASCCP)-sponsored consensus guidelines for management of cervical cancer screening abnormalities, after the original consensus conferences in 20011 and subsequent updates in 20062 and 2012.3 An interim guidance publication providing management recommendations for primary HPV screening was released in 2015.4 This document updates and replaces all previous guidance. The key difference between 2019 guidelines and previous versions is the change from primarily test results–based algorithms (e.g., “Colposcopy is recommended for patients with HPV-positive atypical squamous cells of undetermined significance [ASC-US], low-grade squamous intraepithelial lesion [LSIL],” etc.) to primarily “risk-based” guidelines (e.g., “Colposcopy is recommended for any combination of history and current test results yielding a 4.0% or greater probability of finding CIN 3+,” etc.). See Box 1 for essential changes. Tables of risk estimates for possible combinations of current screening test results and screening history (including unknown history) have been generated from a prospective longitudinal cohort of more than 1.5 million patients followed for more than a decade at Kaiser Permanente Northern California (KPNC). All KPNC estimates of risk underlying guideline decisions are detailed in the accompanying article by Egemen et al.5 The applicability of these risk estimates to other United States regions and populations has been confirmed in other data sets from screening programs and clinical trials.6 Many patients, especially those with minor abnormalities, can be managed by identifying their risk level using Tables 1A to 5B in Egemen et al5 and linking it to a recommended clinical action (return to routine screening, surveillance with repeat testing at 1- or 3-year intervals, colposcopy, or treatment). To facilitate use of these tables, the same information will be accessible via smartphone app (for purchase) and web (no cost) through http://www.asccp.org. Decision aids may facilitate use of the tables.7 Common abnormalities are managed using risk estimates outlined in Section E, and rare abnormalities are managed via the result-specific consensus recommendations outlined in Sections G-K. Box 1. Essential Changes From Prior Management Guidelines 1) Recommendations are based on risk, not results. Recommendations of colposcopy, treatment, or surveillance will be based on a patient's risk of CIN 3+ determined by a combination of current results and history (including unknown history). The same current test results may yield different management recommendations depending on the history of recent past test results. 2) Colposcopy can be deferred for certain patients. Repeat HPV testing or cotesting at 1 year is recommended for patients with minor screening abnormalities indicating HPV infection with low risk of underlying CIN 3+ (e.g., low-grade cytologic abnormalities after a documented negative screening HPV test or cotest). At the 1-year follow-up test, referral to colposcopy is recommended if results remain abnormal. 3) Guidance for expedited treatment is expanded (i.e., treatment without colposcopic biopsy). Expedited treatment was an option for patients with HSIL cytology in the 2012 guidelines; this guidance is now better defined. For nonpregnant patients 25 years or older, expedited treatment, defined as treatment without preceding colposcopic biopsy demonstrating CIN 2+, is preferred when the immediate risk of CIN 3+ is ≥60%, and is acceptable for those with risks between 25% and 60%. Expedited treatment is preferred for nonpregnant patients 25 years or older with high-grade squamous intraepithelial lesion (HSIL) cytology and concurrent positive testing for HPV genotype 16 (HPV 16) (i.e., HPV 16–positive HSIL cytology) and never or rarely screened patients with HPV-positive HSIL regardless of HPV genotype. Shared decision-making should be used when considering expedited treatment, especially for patients with concerns about the potential impact of treatment on pregnancy outcomes. 4) Excisional treatment is preferred to ablative treatment for histologic HSIL (CIN 2 or CIN 3) in the United States. Excision is recommended for adenocarcinoma in situ (AIS). 5) Observation is preferred to treatment for CIN 1. Treatment remains acceptable for patients with repeat diagnoses of CIN 1 persisting 2 years or more. 6) Histopathology reports based on Lower Anogenital Squamous Terminology (LAST)/World Health Organization (WHO) recommendations for reporting histologic HSIL should include CIN 2 or CIN 3 qualifiers, i.e., HSIL(CIN 2) and HSIL (CIN 3). 7) All positive HPV tests, regardless of genotype, should have additional reflex triage testing performed from the same laboratory specimen (e.g., reflex cytology). Additional testing from the same laboratory specimen is recommended because the findings may inform colposcopy practice. For example, those with HSIL cytology and concurrent positive testing for HPV genotype 16 qualify for expedited treatment. HPV 16 or 18 infections have the highest risk for CIN 3 and occult cancer, so additional evaluation (e.g., colposcopy with biopsy) is necessary even when cytology results are negative. If HPV 16 and 18 testing is positive, and additional laboratory testing of the same sample is not feasible, the patient should proceed directly to colposcopy. 8) Continued surveillance with HPV testing or cotesting at 3-year intervals for at least 25 years is recommended after treatment of histologic HSIL, CIN 2, CIN 3, or AIS. Continued surveillance at 3-year intervals beyond 25 years is acceptable for as long as the patient's life expectancy and ability to be screened are not significantly compromised by serious health issues. The 2012 guidelines recommended return to 5-year screening intervals and did not specify when screening should cease. New evidence indicates that risk remains elevated for at least 25 years, with no evidence that treated patients ever return to risk levels compatible with 5-year intervals. Surveillance with cytology alone is acceptable only if testing with HPV or cotesting is not feasible. Cytology is less sensitive than HPV testing for detection of precancer and is therefore recommended more often. Cytology is recommended at 6-month intervals when HPV testing or cotesting is recommended annually. Cytology is recommended annually when 3-year intervals are recommended for HPV or cotesting. 9) Human papilloma virus assays that are Food and Drug Administration (FDA)-approved for screening should be used for management according to their regulatory approval in the United States. (Note: all HPV testing in this document refers to testing for high-risk HPV types only). For all management indications, HPV mRNA and HPV DNA tests without FDA approval for primary screening alone should only be used as a cotest with cytology, unless sufficient, exceptionally rigorous data are available to support primary HPV testing in management. The minimum amount of data required to generate a recommendation will include the patient's age and current test results, as we recognize that previous screening history is often not known. Increased precision of management guidance will be possible if information is available on test results within the past 5 years and previous precancer treatment within the past 25 years.3 Current results and past history are designed to generate the patient's risk estimate from data tables.5 Risk estimates are available for the following clinical situations: abnormal screening test results with unknown history, abnormal screening test results with medical record documentation of a preceding negative HPV test or cotest, surveillance of previous abnormal screening test results that did not require immediate colposcopic referral (e.g., follow-up after an HPV-positive cytology negative result), colposcopy/biopsy results, and follow-up surveillance tests after colposcopy or after treatment for, or resolution of, high-grade abnormalities (e.g., CIN 2+). The recognition that persistent HPV infection is necessary for developing precancer and cancer (defined as CIN 3+, which includes diagnoses of CIN 3, AIS, and cancer) underlies the 2019 guideline update. Prospective longitudinal data indicate that when a new abnormal screening test result follows a negative HPV test or cotest within the past 5 years, the estimated risk of CIN 3+ is reduced by approximately 50%.8 A negative cytology result within 3 years of a new abnormal screening test, however, does not confer a similar reduction in risk.9 The 2019 guidelines also recognize that a colposcopic examination performed according to accepted standards (e.g., using the KPNC colposcopy protocol or the ASCCP Colposcopy Standards10) confirming low-grade or normal histology reduces a patient's estimated risk of having precancer/cancer in the next 2 years.11 This allows patients with an HPV-positive ASC-US or LSIL result at their 1-year follow-up visit after a colposcopy confirming normal- or low-grade histology to return for repeat HPV or cotesting in 1 more year, rather than immediately return to colposcopy. Thus, incorporating a patient's history of previous HPV tests and colposcopy/biopsy results will permit detection and treatment of CIN 3+ while avoiding unnecessary interventions for patients with new HPV infections who are at lower risk.12

Objectives This study explores the association between combination antiretroviral therapy (cART) and oral health outcomes (dental and periodontal) among perinatally HIV-infected (PHIV) youth. Methods We conducted a cross-sectional study of oral health among PHIV youth participating in the Oral Health substudy of the Pediatric HIV/AIDS Cohort Study (PHACS). Dentists at research sites were trained/calibrated on how to perform a standardized oral mucosal, dental and periodontal examination. They assessed the decayed-missing-filled-surfaces and teeth index (DMFS/T). The number of decayed surfaces and teeth and the number of teeth with gingival bleeding on probing for each participant were derived from the examination. Data for analysis included lifetime measurements of CD4 cell count and viral load, sociodemographic information and current/past history of ART. Results Among 209 PHIV youth, 95% were on ART at the time of enrolment. Among 143 PHIV youth on the same cART for at least 1 year, we found that the mean decayed teeth score of those receiving cART containing an integrase inhibitor was 86% higher than that of those on cART without an integrase inhibitor after adjusting for age, lifetime proportion of unsuppressed viral load and CD4 cell count nadir. Initiating protease inhibitors before age 6 years was associated with a significantly lower DMFT score than participants who initiated at age 6 years and older. Conclusion Our study revealed that PHIV youth who received cART containing an integrase inhibitor had a significantly higher number of untreated active caries than those on cART without an integrase inhibitor. This may warrant closer dental surveillance of those receiving an integrase inhibitor.

When should young women begin cervical cancer screening? Dr. Moscicki states that we should continue to initiate screening before the age of 25 years in the US. The reasons include a lower rate of HPV vaccination among the current generation of young adult women and increases in invasive cervical cancer cases in countries that have raised the screening age to 25 years. She further cites specific shortcomings of the US healthcare system that can contribute to underscreening among young women, including fragmented healthcare, lack of health insurance, and a rapidly declining rate of pelvic examinations for cervical cancer screening among this age group, despite current guidelines that continue to recommend screening. She posits that although cervical cancer is rare among women aged 21 to 24 years, promoting screening in this age group acts as a safety net to prevent cancers among women aged 25 to 29 years.

The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of colposcopy and directed biopsy for cervical cancer prevention in the United States (US). The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. An extensive literature review was conducted and supplemented by a systematic review and meta-analysis of unpublished data. In addition, a survey of practicing colposcopists was conducted to assess current colposcopy practice in the US. Recommendations were approved by the working group members, and the final revisions were made based on comments received from the public. The recommendations cover terminology, risk-based colposcopy, colposcopy procedures, and colposcopy adjuncts. The ASCCP Colposcopy Standards recommendations are an important step toward raising the standard of colposcopy services delivered to women in the US. Because cervical cancer screening programs are currently undergoing important changes that may affect colposcopy performance, updates to some of the current recommendations may be necessary in the future.

In contrast to high rates of oral human papillomavirus (HPV) found in human immunodeficiency virus (HIV)-infected adults, only 2% of 209 perinatally HIV-infected youth had oral HPV. This rate was similar in HIV-exposed but uninfected youth. No association was found with sexual activity; however, low CD4 counts were associated with oral HPV.

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. CA Cancer J Clin 2012;62:147-172. V C

OBJECTIVE: Higher rates of human papillomavirus (HPV) in adolescents and younger women have been attributed to their greater extent of “cervical ectopy,” defined as columnar and metaplastic epithelia on the ectocervix. Our objective was to estimate associations between ectopy and incident HPV in healthy adolescents and young women. METHODS: Enrolled between October 2000 and October 2002, this prospective cohort included women aged 13–21 years who were sexually active, without previous cervical intraepithelial neoplasia, cervical procedures, or immunosuppression, with menarche within 6 years before enrollment, and negative for HPV DNA at baseline. Every 4 months, extent of ectopy was quantitatively measured using colpophotography and computerized planimetry. Cox proportional hazards models examined associations between ectopy and incident HPV, defined as the first positive HPV result during follow-up. RESULTS: The 138 women attended 509 total visits. At baseline, mean age was 16.7 years and mean extent of ectopy was 25% of the total cervical face. Incident HPV of any type was detected in 42 (30%) women and was not significantly associated with baseline ectopy (hazard ratio 1.09, 95% confidence interval 0.96–1.25; P=.20; ectopy in units of 10%), or with ectopy measured 4 months before HPV detection (hazard ratio 1.09, confidence interval 0.94–1.26; P=.25). Our sample size had 80% power to detect a hazard ratio of 1.9 (with two-tailed α=0.05). Results were similarly insignificant for HPV subgroupings of incident high-risk, low-risk, α9, and α3/α15 types, and when adjusted for new sexual partners. CONCLUSION: Extent of cervical ectopy was not associated with HPV acquisition in healthy adolescents and young women. Biological vulnerabilities may lie in immune function or other characteristics of the cervical epithelium. LEVEL OF EVIDENCE: II

HPV 6 and 11 cause greater than 90% of genital warts in males and females. Data show that approximately 3–4 million cases of genital warts in men occur each year with a peak rate of 500 per 100,000 in the 25–29 year old group. (1) The majority of these genital warts are diagnosed in men under the age of 30 years. In addition to genital warts, men are at risk for several HPV-related morbidities including penile, anal and oral cancers.

To describe the natural history of cervical intraepithelial neoplasia (CIN) 2 in a prospective study of adolescents and young women, and to examine the behavioral and biologic factors associated with regression and progression.Adolescents and women aged 13 to 24 years who were referred for abnormal cytology and were found to have CIN 2 on histology were evaluated at 4-month intervals. Risks for regression were defined as three consecutive negative cytology and histology visits, and progression to CIN 3 was estimated using Cox proportional hazards regression models.Ninety-five patients with a mean age of 20.4 years (±2.3) were entered into the analysis. Thirty-eight percent resolved by year 1, 63% resolved by year 2, and 68% resolved by year 3. Multivariable analysis found that recent Neisseria gonorrhoeae infection (hazard ratio 25.27; 95% confidence interval [CI] 3.11-205.42) and medroxyprogesterone acetate use (per month) (hazard ratio 1.02; 95% CI 1.003-1.04) were associated with regression. Factors associated with nonregression included combined hormonal contraception use (per month) (hazard ratio 0.85; 95% CI 0.75-0.97) and persistence of human papillomavirus (HPV) of any type (hazard ratio 0.40; 95% CI 0.22-0.72). Fifteen percent of patients showed progression by year 3. HPV 16/18 persistence (hazard ratio 25.27; 95% CI 2.65-241.2; P=.005) and HPV 16/18 status at last visit (hazard ratio 7.25; 95% CI 1.07-49.36; P.05) were associated with progression Because of the small sample size, other covariates were not examined.The high regression rate of CIN 2 supports clinical observation of this lesion in adolescents and young women.

To determine whether healthy, young women in sub-Saharan Africa have a more activated immune milieu in the genital tract (i.e. activated CD4 T cells) than a similar population in the United States.A cross-sectional study nested in a phase 1 microbicide trial.Cervical cytobrushes were collected from 18 to 24-year-old women in San Francisco, California, USA (n = 18) and Kisumu, Kenya (n = 36) at enrollment into a phase 1 microbicide trial. All participants tested negative for HIV, herpes simplex virus 2, gonorrhea, chlamydia, and trichomonas, and had abstained from sex for at least 7 days prior to enrollment. Cryopreserved T-cell populations were assayed by flow cytometry in a central laboratory. Secretory leukocyte protease inhibitor levels were assayed in cervicovaginal lavage samples. The Wilcoxon rank-sum test was used to compare immune parameters between sites.The total number of endocervical CD4(+) T cells was slightly higher in participants from San Francisco, but participants from Kisumu had a substantially higher number and proportion of CD4(+) T cells expressing the early activation marker CD69, with and without the HIV coreceptor C-C chemokine receptor type 5, and a greater proportion of activated CD8(+) T cells. Median (interquartile range) genital levels of secretory leukocyte protease inhibitor were lower in participants from Kisumu compared with those from San Francisco [190 (96-519) vs. 474 (206 817) pg/ml, P0.03].Activated mucosal T cells were increased in the genital tract of young, sexually transmitted infection/HIV-free Kenyan women, independent of common genital coinfections, and secretory leukocyte protease inhibitor levels were reduced. The cause of these mucosal immune differences is not known, but could partly explain the high HIV incidence in young women from sub-Saharan Africa.

Although cervical cytology screening programs have dramatically decreased rates of invasive cancer in developed countries most guidelines in the USA were overaggressive in their management of abnormal cytology in adolescents and young women. These management strategies resulted in costly over-treatment. The purpose of this article is to review the evidence for the new guidelines in cytology screening in youth. Natural history studies of human papillomavirus (the cause of abnormal cytology and cervical cancer) suggest there is little risk of a significant pre-cancerous lesion going undetected within the first 3–5 years after the onset of sexual activity. The American Cancer Society now recommends that screening be initiated within 3 years of the onset of vaginal intercourse but no later than 21 years of age. The American Society for Colposcopy and Cervical Pathology allows for follow-up of low-grade squamous intra-epithelial lesions with repeat cytology or human papillomavirus DNA testing rather than immediate referral to colposcopy. The new recommendations appear to be safe and will decrease the current over-referral and over-treatment of adolescents and young women with HPV infections. (authors)

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical neoplasia and cancer, based on recommendations from a formal review and recent workshop, is presented. The new screening recommendations address when to begin screening, when screening may be discontinued, whether to screen women who have had a hysterectomy, appropriate screening intervals, and new screening technologies, including liquid-based cytology and HPV DNA testing.

Objective: To examine the prevalence of and risk for anal human papillomavirus (HPV) infection and abnormal anal cytology in sexually active adolescents. Design: Prevalence data from adolescents aged 13–18 years with and without HIV infection and with a history of high-risk sexual behavior. Methods: HPV DNA was detected using amplification techniques. Abnormal anal cytology was defined as atypical squamous cell of undetermined significance or worse. Results: Prevalence of anal HPV infection was similar in HIV-infected [28/58 (48%)] and uninfected [9/25 (36%)] boys (P = 0.3) but greater in HIV-infected [59/183 (59%)] than in uninfected [11/82 (13%)] girls (P < 0.001). Perianal warts were a risk for anal HPV in both boys [odds ratio (OR) 15.5; 95% confidence interval (CI) 1.6–149] and girls (OR 9.9; 95% CI 1.9–51.3). In subjects without anal warts HIV infection was significant for girls (OR 2.3; 95% CI 1.1–4.9) and homosexual/bisexual orientation was significant for boys (OR 5.2; 95% CI 1.3–20.6). Abnormal anal cytology was more common among boys [32/77 (41.6%)] than girls [38/230 (16.5%)] (P

The objective was to examine potential hematologic and immunologic markers for healthy adolescents and for adolescents infected with HIV. The REACH Project (Reaching for Excellence in Adolescent Care and Health) of the Adolescent Medicine HIV/AIDS Research Network (AMHARN) recruits HIV-infected and high-risk HIV-uninfected adolescents aged at least 13 but less than 19 years. The study evaluates biomedical and behavioral features of HIV infection as observed while under medical care for HIV infection and adolescent health. Blood samples were collected from HIV-infected and HIV-uninfected subjects at 16 clinical sites. Cell phenotypes were determined using standard single dual or three-color flow cytometry. This report includes data at enrollment for 94 HIV-positive adolescents who had never received antiretroviral therapy (ART) (mean age 17.4 ± 1.0 years for males and 16.5 ± 1.3 years for females) and 149 HIV-negative adolescents (mean age 16.7 ± 1.2 years for males and 16.6 ± 1.2 years for females); this is the antiretroviral therapy-naive subset drawn from 294 HIV-positive and 149 HIV-negative adolescents enrolled in the REACH Cohort. The total leukocyte count was significantly reduced in the HIV-positive females in comparison with the HIV-negative females (P < 0.001). There was a reduction in natural killer cells (P < 0.05) in HIV-positive females (mean 140.6 ± 104.2 x 10/6 cells/l) in comparison with HIV-negative females (184.3 ± 142.5 x 10/6 cells/l) whereas no differences were found between the two groups of males. The reduction in the total CD4 cell count in HIV-positive males and females in comparison with the HIV-negative subjects was the consequence of a decrease in both the naive CD4 and memory CD4 components. There was a striking increase in the mean number of CD8 memory cells in HIV-positive compared with HIV-negative adolescents and a corresponding increase in the percentage of these cells. In contrast naive CD8 cells were present in increased numbers but their percentage was decreased. These studies of adolescents provide normative data for high-risk healthy adolescents as well as baseline immunologic data for a cohort of ART-naive HIV-positive adolescents. This comparison suggests that this untreated recently infected group had relatively intact immunologic parameters. (authors)

OBJECTIVE To determine the variability in human papillomavirus (HPV) DNA testing of the cervix in young women found positive for HPV DNA by dot blot hybridization on routine examination. METHODS Young women who were found to be HPV DNA-positive on routine screening using an RNA-DNA dot blot hybridization method were asked to return for repeat HPV DNA sampling, cytology, colposcopic examination, and biopsy if indicated. Those who had no histologic evidence of cervical dysplasia were asked to return every 4 months for cytology and HPV DNA testing using standardized RNA-DNA hybridization and polymerase chain reaction techniques. RESULTS The women were followed for a mean of 27.6 months (range 13-40) with a mean of six visits (range four to ten). One-third of the women remained consistently or intermittently HPV DNA-positive by RNA-DNA dot blot hybridization, and almost 50% of the women remained consistently or intermittently positive using polymerase chain reaction techniques. Women were more likely to be positive by polymerase chain reaction than by RNA-DNA hybridization at both 1 year and after 2 years of follow-up (P < .05). However, rates for persistent positive tests by either method were similar at 1 and 2 years of follow-up. Forty percent of the subjects had new or different types than the original HPV type appear during follow-up. All five women who had evidence of spontaneous regression of cytologic abnormalities became HPV DNA-negative by both methods. CONCLUSIONS Our data suggest that a portion of women infected with HPV appear to eliminate the infection over a relatively short period and are at low or no risk of developing disease. Persistent DNA negativity was also found in those women undergoing spontaneous regression. However, a substantial proportion of women remained intermittently positive by RNA-DNA hybridization and polymerase chain reaction. This finding suggests that the virus remains latent in some individuals and may undergo reactivation, defined by sufficient replication to allow detection by means less sensitive than polymerase chain reaction.