Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2.

BACKGROUND: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression. OBJECTIVE: This study aimed to describe human papillomavirus HPV type-specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. STUDY DESIGN: We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF10-DEIA-LiPA25 system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model. RESULTS: A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37-1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03-1.61), whereas no differences were observed across age groups. CONCLUSION: The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women.

Trends in Adolescent Human Papillomavirus Vaccination and Parental Hesitancy in the United States.

BACKGROUND: Human papillomavirus (HPV) vaccination coverage remains suboptimal in the United States, underscoring the importance of monitoring trends in vaccine hesitancy. METHODS: Cross-sectional data from the 2011-2020 National Immunization Survey-Teen were used to assess trends in HPV vaccination initiation among 13-17-year-olds, parental intent to initiate vaccination, and primary reasons for parental hesitancy. RESULTS: Among all sex and race and ethnicity groups, the prevalence of HPV vaccination initiation increased over time, but parental intent to vaccinate against HPV for unvaccinated teens remained consistently low (≤45%). Among hesitant parents, "safety concerns" increased in nearly all demographic groups, with the greatest increases observed for non-Hispanic white female and male teens and no change for non-Hispanic black female teens. In 2019-2020, parents of unvaccinated non-Hispanic white teens were least likely to intend on vaccinating their teens, and the most common reason for hesitancy varied by sex and race and ethnicity (eg, "safety concerns" for white teens and "not necessary" for black female teens). CONCLUSIONS: Although HPV vaccination initiation increased over time, a substantial fraction of parents remain hesitant, and trends in their reason varied by sex and race and ethnicity. Health campaigns and clinicians should address vaccine safety and necessity.

Adolescent vaccination against human papillomavirus (HPV) is a critical tool for cancer prevention. We analyzed trends in HPV vaccination initiation among adolescents aged 13­17 years and trends in parental hesitancy to initiate HPV vaccination for their teen, using data from a national survey in the United States. Between 2011­2012 and 2019­2020, adolescent HPV vaccination initiation increased over time for both female teens (from 53.4% to 75.2%) and male teens (from 14.5% to 71.5%). However, the majority of parents/guardians of unvaccinated teens did not intend to vaccinate their teen against HPV (ie, were vaccine hesitant), and this was consistent over time in all sex and race and ethnicity groups. Among hesitant parents, the proportion reporting safety concerns as their main reason for being hesitant increased over time in nearly all demographic groups, with the greatest increases in this reasoning observed for white teens. In 2019­2020, parents of unvaccinated white teens were most likely to be vaccine hesitant. The most common reason for being vaccine hesitant also differed by sex and race and ethnicity. Although HPV vaccination has been shown to be safe and effective, HPV vaccination coverage remains suboptimal, and a substantial fraction of parents/guardians continue to be hesitant to adolescent HPV vaccination.

Clinical course of cervical intraepithelial neoplasia grade 2: a population-based cohort study.

BACKGROUND: Cervical intraepithelial neoplasia grade 2 has historically been the threshold for surgical excision, but because of high regression rates, many countries are transitioning to active surveillance. However, estimates for regression rates are based on small studies with heterogeneous definitions of regression and progression. OBJECTIVE: This study aimed to describe regression and progression rates of cervical intraepithelial neoplasia grade 2 using nationwide healthcare registry data. STUDY DESIGN: This was a nationwide population-based cohort study on women aged 18 to 40 years who had undergone active surveillance for cervical intraepithelial neoplasia grade 2 in Denmark from 1998 to 2020. This study excluded women with a previous record of cervical intraepithelial neoplasia grade 2 or worse or surgical excision. Cumulative incidence functions were used to estimate the rates of regression and progression at 6, 12, 18, and 24 months after diagnosis. In addition, a modified Poisson regression was used to estimate the crude and adjusted relative risks of progression within 24 months stratified by index cytology and age. RESULTS: During the study period, 11,056 women underwent active surveillance, 6767 of whom regressed and 3580 of whom progressed within 24 months. This corresponded to regression rates of 62.9% (95% confidence interval, 61.9-63.8) and progression rates of 33.3% (95% confidence interval, 32.4-34.2) at 24 months of follow-up. Most women regressed (90%) or progressed (90%) within the first 12 months. Women with high-grade index cytology had a higher risk of progression than women with normal index cytology (adjusted relative, 1.58; 95% confidence interval, 1.43-1.76), whereas there was no difference in the risk of progression between women aged 30 and 40 years and women aged 23 to 29 years (adjusted relative risk, 0.98; 95% confidence interval, 0.88-1.10). CONCLUSION: The observed high regression rates of cervical intraepithelial neoplasia grade 2 supported the transition in clinical management from surgical excision to active surveillance, particularly among women with low-grade or normal index cytology.

"Day or night, no matter what, I will go": Women's perspectives on challenges with follow-up care after cervical cancer screening in Iquitos, Peru: a qualitative study.

BACKGROUND: The study's objective was to explore the factors associated with loss to follow-up among women with abnormal cervical cancer screening results in Iquitos, Peru from women's perspectives. METHODS: In-depth interviews were conducted with 20 screen-positive women who were referred for follow-up care but for whom evidence of follow-up was not found. Interview transcripts were thematically analyzed inductively, and the codes were then categorized using the Health Care Access Barriers Model for presentation of results. RESULTS: All interviewed women were highly motivated to complete the continuum of care but faced numerous barriers along the way, including cognitive barriers such as a lack of knowledge about cervical cancer and poor communication from health professionals regarding the process, structural barriers such as challenges with scheduling appointments and unavailability of providers, and financial barriers including out-of-pocket payments and costs related to travel or missing days of work. With no information system tracking the continuum of care, we found fragmentation between primary and hospital-level care, and often, registration of women's follow-up care was missing altogether, preventing women from being able to receive proper care and providers from ensuring that women receive care and treatment as needed. CONCLUSIONS: The challenges elucidated demonstrate the complexity of implementing a successful cervical cancer prevention program and indicate a need for any such program to consider the perspectives of women to improve follow-up after a positive screening test.

"Easy women get it": pre-existing stigma associated with HPV and cervical cancer in a low-resource setting prior to implementation of an HPV screen-and-treat program.

BACKGROUND: Cervical cancer is preventable with vaccination and early detection and treatment programs. However, for these programs to work as intended, stigma related to HPV and cervical cancer must be understood and addressed. We explored pre-existing stigma associated with HPV and cervical cancer in the public healthcare system and community of a low-resource setting prior to implementation of an HPV screen-and-treat program. METHODS: This study conducted thematic analysis of data collected during implementation of a novel HPV screen-and-treat system for cervical cancer early detection and treatment in Iquitos, Peru. We included 35 semi-structured interviews (19 health professionals, 16 women with cervical precancer or cancer), eight focus groups (70 community women), one workshop (14 health professionals), 210 counseling observations (with 20 nurse-midwives), and a document review. We used the Socio-Ecological Model to organize the analysis. RESULTS: We identified three main themes: 1. the implication that women are to blame for their HPV infection through characterizations of being easy or promiscuous, 2. the implication that men are to blame for women's HPV infections through being considered careless or unfaithful, 3. HPV is shameful, embarrassing, and something that should be hidden from others. Consequently, in some cases, women refrained from getting screened for HPV. These themes were seen at the individual level among women, relationship level among women, men, and family members, community level among healthcare staff, and societal level within components of cervical cancer guidelines and male chauvinism. CONCLUSIONS: Cervical cancer early detection and treatment programs in limited resource settings must address stigma entrenched throughout the entire healthcare system and community in order to sustainably and successfully implement and scale-up new programs. Interventions to tackle this stigma can incorporate messages about HPV infections and latency to lessen the focus on the influence of sexual behavior on HPV acquisition, and instead, promote screening and treatment as paramount preventative measures.

Evidence of latent HPV infection in older Danish women with a previous history of cervical dysplasia.

INTRODUCTION: Understanding whether human papillomavirus (HPV) may establish latency in the uterine cervix is important. A better understanding of HPV natural history is useful for clinical counseling of women attending screening and to accurately inform health prevention strategies such as screening and HPV vaccination. We evaluated the extent of latent HPV infections in older women with a history of abnormal cytology. MATERIAL AND METHODS: We conducted a cross-sectional study in Aarhus, Denmark, from March 2013 through April 2015. Women were enrolled if they underwent cervical amputation or total hysterectomy because of benign disease. Prior to surgery, women completed a questionnaire and a cervical smear was collected for HPV testing and morphological assessment. For evaluation of latency (i.e., no evidence of active HPV infection, but HPV detected in the tissue), we selected women with a history of abnormal cervical cytology or histology, as these women were considered at increased risk of harboring a latent infection. Cervical tissue underwent extensive HPV testing using the SPF10-DEIA-LipA25 assay. RESULTS: Of 103 women enrolled, 26 were included in this analysis. Median age was 55 years (interquartile range [IQR] 52-65), and most women were postmenopausal and parous. The median number of sexual partners over the lifetime was six (IQR 3-10), and 85% reported no recent new sexual partner. Five women (19.2%) had evidence of active infection at the time of surgery, and 19 underwent latency evaluation. Of these, a latent infection was detected in 11 (57.9%), with HPV16 being the most prevalent type (50%). Nearly 80% (n = 14) of the 18 women with a history of previous low-grade or high-grade cytology with no treatment had an active or latent HPV infection, with latent infections predominating. HPV was detected in two of the six women with a history of high-grade cytology and subsequent excisional treatment, both as latent infections. CONCLUSIONS: HPV can be detected in cervical tissue specimens without any evidence of an active HPV infection, indicative of a latent, immunologically controlled infection. Modeling studies should consider including a latent state in their model when estimating the appropriate age to stop screening and when evaluating the impact of HPV vaccination.

Women's perspectives on the acceptability and feasibility of an HPV screen-and-treat approach to cervical cancer prevention in Iquitos, Peru: a qualitative study.

BACKGROUND: The objective of this study was to explore women's experiences of a screen-and-treat approach with ablative therapy (referred to by the Spanish acronym TVT-TA) as a method of treatment following a positive HPV test in Iquitos, Peru. METHODS: A total of 111 in-depth interviews were conducted with 47 HPV positive women who attended the TVT-TA procedure at a primary-level healthcare facility. Interviews were conducted immediately before, immediately after, and six-weeks after TVT-TA. RESULTS: Most interviewed women reported experiencing moderate pain during ablative therapy and minimal pain immediately after and six weeks after ablative therapy. Women also stated that the pain was less intense than they had expected. The most common physical after-effects of treatment were bleeding and vaginal odor. Women experienced oscillating emotions with fear upon receiving a positive HPV result, calming after hearing about ablative therapy treatment, worry about pain from the treatment itself, relaxation with counseling about the procedure, and relief following treatment. CONCLUSIONS: Nearly all participants emphasized that they were pleased with the TVT-TA process even if they had experienced pain during TVT-TA, recommended that TVT-TA be expanded and available to more women, and stated that TVT-TA was faster and easier than expected. This study found that TVT-TA is a feasible and acceptable means of treating HPV according to the women receiving the treatment.

Rates of New Human Papillomavirus Detection and Loss of Detection in Middle-aged Women by Recent and Past Sexual Behavior.

BACKGROUND: Understanding the source of newly detected human papillomavirus (HPV) in middle-aged women is important to inform preventive strategies, such as screening and HPV vaccination. METHODS: We conducted a prospective cohort study in Baltimore, Maryland. Women aged 35-60 years underwent HPV testing and completed health and sexual behavior questionnaires every 6 months over a 2-year period. New detection/loss of detection rates were calculated and adjusted hazard ratios were used to identify risk factors for new detection. RESULTS: The new and loss of detection analyses included 731 women, and 104 positive for high-risk HPV. The rate of new high-risk HPV detection was 5.0 per 1000 woman-months. Reporting a new sex partner was associated with higher detection rates (adjusted hazard ratio, 8.1; 95% confidence interval, 3.5-18.6), but accounted only for 19.4% of all new detections. Among monogamous and sexually abstinent women, new detection was higher in women reporting ≥5 lifetime sexual partners than in those reporting <5 (adjusted hazard ratio, 2.2; 95% confidence interval, 1.2-4.2). CONCLUSION: Although women remain at risk of HPV acquisition from new sex partners as they age, our results suggest that most new detections in middle-aged women reflect recurrence of previously acquired HPV.

Importance of Lifetime Sexual History on the Prevalence of Genital Human Papillomavirus (HPV) Among Unvaccinated Adults in the National Health and Nutrition Examination Surveys: Implications for Adult HPV Vaccination.

BACKGROUND: Although the United States Food and Drug Administration recently approved the human papillomavirus (HPV) vaccine for individuals aged 27-45 years, the Centers for Disease Control and Prevention did not change its guidelines for routine HPV vaccination. Since recommendations for adult vaccination emphasize shared clinical decision-making based on risk of new infections, we examined the relationship between HPV prevalence and sexual behavior. METHODS: This study was conducted among 5093 HPV-unvaccinated, sexually experienced adults aged 18-59 years in the National Health and Nutrition Examination Surveys (2013-2016). For each sex and age group, adjusted prevalences of 9-valent vaccine-specific, high-risk, and any HPV infection were estimated by number of lifetime sexual partners (LTSPs) using logistic regression. An analysis restricted to persons who did not have a new sexual partner in the past year (ie, removing those at highest risk of newly acquired HPV) was also conducted. RESULTS: In each age group, genital HPV prevalence was higher among persons with >5 LTSPs compared with 1-5 LTSPs in both males and females. There were only slight reductions in HPV prevalence after removing participants who reported a new sexual partner in the past year. For example, among females aged 27-45 years with >5 LTSPs, the adjusted prevalence of 9-valent vaccine-type HPV infection was 13.4% (95% confidence interval [CI], 9.9%-17.0%) in the full population compared to 12.1% (95% CI, 8.8%-15.4%) among those with no new sexual partners. CONCLUSIONS: Prevalent HPV infection was primarily reflective of cumulative exposures over time (higher LTSPs). New exposures had limited impact, emphasizing the need to consider sexual history in the decision-making process for adult HPV vaccination.

Burden of Mycoplasma genitalium and Bacterial Coinfections in a Population-Based Sample in New Mexico.

ABSTRACT: In this population-based US study, the overall prevalence of Mycoplasma genitalium was 1.95% (95% confidence interval [CI], 1.62%-2.34%), declining from 6.12% (95% CI, 4.72%-7.92%) in women aged 21 to 24 years to 0.48% (95% CI, 0.25%-0.94%) in women aged 40 to 64 years. The prevalence of coinfections with Chlamydia trachomatis and Trichomonas vaginalis was low.

Achieving equity in cervical cancer screening in low- and middle-income countries (LMICs): Strengthening health systems using a systems thinking approach.

The World Health Organization (WHO) is leading a call to action to eliminate cervical cancer by the end of the century through global implementation of two effective evidence-based preventive interventions: HPV vaccination and cervical screening and management (CSM). Models estimate that without intervention, over the next 50 years 12.2 million new cases of cervical cancer will occur, nearly 60% of which are preventable only through CSM. Given that more than 80% of the cervical cancer occurs in low- and middle-income countries (LMICs), scaling up sustainable CSM programs in these countries is a top priority for achieving the global elimination goals. Multiple technologies have been developed and validated to meet this need. Now it is critical to identify strategies to implement these technologies into complex, adaptive health care delivery systems. As part of the coordinated cervical cancer elimination effort, we applied a systems thinking lens to reflect on our experiences with implementation of HPV-based CSM programs using the WHO health systems framework. While many common health system barriers were identified, the effectiveness of implementation strategies to address them was context dependent; often reflecting differences in stakeholder's belief in the quality of the evidence supporting a CSM algorithm, the appropriateness of the evidence and algorithm to context, and the 'implementability' of the algorithm under realistic assessments of resource availability and constraints. A structured planning process, with early and broad stakeholder engagement, will ensure that shared-decisions in CSM implementation are appropriately aligned with the culture, values, and resource realities of the setting.

Knowledge, attitudes, and practices of cervical cancer prevention and pap smears in two low-income communities in Lima, Peru.

BACKGROUND: Cervical cancer is a leading cause of death among Peruvian women. Barriers at multiple levels impact effective screening and treatment, including a lack of knowledge about cervical cancer and how regular screening can reduce morbidity and mortality through earlier detection. The aim of this study is to assess knowledge, attitudes, and practices regarding cervical cancer and its prevention in the peri-urban communities of Oasis and Pampas in southern Lima, Peru that can be used to inform future campaigns about cervical cancer prevention. METHODS: A cross-sectional survey that included several open-ended questions was administered to women in Pampas and Oasis between 2015 and 2016 to evaluate the knowledge, attitudes, and practices regarding cervical cancer and Pap smears. RESULTS: In total, 224 women were interviewed. Knowledge about cervical cancer and Pap smears was high, and attitudes were predominantly positive among most participants. Most participants knew how often they should get Pap smears (89.7%), when to begin seeking screening (74.6%), knew the price of a Pap smear (61.9%), and felt Pap smears were important for their health (70.1%). About one third (29.5%) of premenopausal women reported receiving a Pap smear in the last year. However, open ended questions revealed some knowledge gaps around Pap smears, as well as some stigma associated to Human Papilloma Virus (HPV) infection. CONCLUSION: Although knowledge of cervical cancer prevention was generally high and perceptions were positive among women in peri-urban Peruvian communities, our findings revealed there is a need for education on HPV infection prevalence among sexually active individuals to reduce stigma. Future research should focus on exploring experiences with follow-up and treatment associated with abnormal Pap smears, as well as perspectives from health authorities and professionals about barriers in the early detection and treatment process for cervical cancer.

A study of the risks of CIN3+ detection after multiple rounds of HPV testing: Results of the 15-year cervical cancer screening experience at Kaiser Permanente Northern California.

Many countries are transitioning to HPV testing for cervical cancer screening, despite a lack of long-term experience. To anticipate multi-round screening performance, we analyzed 15-year HPV testing results at Kaiser Permanente Northern California (KPNC). We evaluated HPV test result patterns among women aged 30-64 undergoing triennial HPV/cytology cotesting at KPNC during 2003-2018. We calculated incidence rates and proportion of CIN3+ diagnoses associated with the most frequent HPV testing patterns overall and stratified by age. From 2003 to 2018, a total of 1,361,581 women had a valid HPV test result, and 7,087 were diagnosed with CIN3+. Incidence rates of CIN3+ after HPV positivity were lowest when HPV detection was new and highest in women with prevalent infections (770 vs. 13,910/100,000 person-years). Repeat test negativity reduced subsequent incidence rates of CIN3+ to extremely low levels (18/100,000 person-years following four consecutive negative results). For mixed patterns of positivity/negativity, the recency and frequency of positive tests were associated with increased rates of CIN3+ diagnosis. Most CIN3+ cases (76%) were diagnosed in women who were positive at baseline (the first known positive HPV result); 16% were attributed to apparent newly detected infections and 3% to possible reappearing infections. These results corroborate previous findings that current HPV positivity, particularly when prevalent rather than new, is associated with the highest rates of CIN3+. In a screening program implementing HPV testing, most CIN3+ is detected at the first HPV positive test.

Hysterectomy-corrected cervical cancer mortality rates in Denmark during 2002-2015: A registry-based cohort study.

INTRODUCTION: We aimed to describe the cervical cancer mortality rates after correcting for hysterectomy and to evaluate trends over calendar time and by age. MATERIAL AND METHODS: Using data from nationwide registries, we calculated uncorrected and hysterectomy-corrected cervical cancer mortality rates among women age ≥20 years in Denmark during 2002-2015. We calculated hysterectomy-corrected rates by subtracting post-hysterectomy person-years from the denominator, unless hysterectomy was performed due to cervical cancer. RESULTS: The age-standardized hysterectomy-corrected cervical cancer mortality rate of 5.8/100 000 was 18.4% higher than the corresponding uncorrected rate. The hysterectomy-corrected cervical cancer mortality rate increased significantly with age, particularly in women aged 65+ (annual percent change +4.57), peaking at 26.1/100 000 person-years in women aged ≥85. The hysterectomy-corrected cervical cancer mortality declined significantly over calendar time, from 6.3/100 000 person-years in 2002 to 4.5/100 000 person-years in 2015 (annual percent change -0.22). This was mainly due to a significant decline in women aged 60 years and older, from 20.4/100 000 person-years in 2003 to 9.3/100 000 person-years in 2015 (annual percent change -0.75). CONCLUSIONS: The mortality of cervical cancer increased significantly by age, particularly among women aged 65 years and older for whom routine cervical cancer screening is not recommended. Understanding reasons for the high mortality rate in older women is critical, as this may help identify interventions needed to ensure a continued decline in cervical cancer mortality in older Danish women.

Barriers and innovative interventions for early detection of cervical cancer.

Cervical cancer has decreased significantly over the past 30 years in some countries. However, it remains among the leading causes of cancer deaths in low-income, and racial/ethnic minority women. Cervical cancer prevention technologies are not always available. Laboratories are often not well equipped to use them. HPV information has not been widely disseminated. WHO guidelines, and US and Latin American data provide context for strategies on effective interventions to reduce cervical cancer disparities. Systemic, personal and cultural barriers, combined with decision-making guidelines, and impactful messaging can accelerate reductions in cervical cancer health inequities in the Americas.

El cáncer cervicouterino ha disminuido significativamente en los últimos 30 años, pero sigue siendo una de las principales causas de muerte entre mujeres de bajos recursos y minorías raciales/étnicas. Las tecnologías preventivas del cáncer cervicouterino no están siempre disponibles y los laboratorios no están siempre bien equipados para utilizarlas. La información sobre el VPH no ha sido difundida ampliamente. La OMS y datos de EEUU y Latinoamérica ofrecen estrategias para reducir el cáncer cervicouterino. El entendimiento de las barreras sistémicas, personales y culturales, dentro de un marco de toma de decisiones, y mensajes innovadores puede reducir las barreras asociadas con el cáncer cervicouterino en las Américas.

Increases in Human Papillomavirus Vaccination Among Adolescent and Young Adult Males in the United States, 2011-2016.

In the United States, human papillomavirus (HPV) vaccination has been recommended for females since 2006 and males since 2011. We assessed temporal trends in HPV vaccine coverage (defined as receipt of ≥1 dose) among 9-26-year-old participants in the 2011-2016 National Health and Nutrition Examination Surveys. While coverage increased overall, from 37.7% to 45.7%, among females (adjusted prevalence difference [aPD], 7.1%; 95% confidence interval [CI], .1%-13.7%), there was no change among female adolescents aged 9-17 years. For males, coverage increased overall, from 7.8% to 27.4% (aPD, 18.8%; 95% CI, 14.1%-23.5%), and among every stratum of age, race/ethnicity, health insurance status, poverty level, and immigration status (P ≤ .05). The increase in HPV vaccine coverage observed among males is encouraging, but coverage remains below national targets for both males and females.

Uptake of HPV testing and extended cervical cancer screening intervals following cytology alone and Pap/HPV cotesting in women aged 30-65 years.

OBJECTIVE: To evaluate the adoption of HPV testing and recommended extended cervical cancer screening intervals in clinical practice, we described yearly uptake of Pap/HPV cotesting and estimated length of time between normal screens by patient characteristics. METHODS: We examined 55,575 Pap/HPV records from 27,035 women aged 30-65 years from the Johns Hopkins Hospital Pathology Data System between 2006 and 2013. Cotest uptake and median times to next screening test for cotests and cytology only were calculated. Adjusted hazard ratios were estimated using Cox proportional hazards models, with random effects adjustment for clustering within clinic. RESULTS: Cotest usage increased from < 10% in 2006 to 78% in 2013. The median time to next screening test following normal cytology alone remained constant around 1.5 years. Screening intervals following a dual-negative cotest increased from 1.5 years in 2006/2007 to 2.5 years in 2010, coincident with increases in the proportion of women cotested. Intervals following a dual negative cotest were longer among Medicare patients (3 years) compared with privately insured women (2.5 years), and shorter among black (2 years) compared with white women (2.8 years). CONCLUSION: By mid-2013 we observed broad adoption of Pap/HPV cotesting in routine screening in a large academic medical center. Increased screening intervals were observed only among cotested women, while those screened by cytology alone continued to be screened almost annually. The influence of different combinations of race and insurance on screening intervals should be further evaluated to ensure balance of screening risks and benefits in the U.S.

How confident can we be in the current guidelines for exiting cervical screening?

Current US guidelines recommend against cervical screening beyond age 65 in women who have had adequate negative screening. In anticipation of the next round of evidence review and guideline updates, we provide a critical review of the evidence supporting the exiting recommendation in the US, highlighting both practice changes and new insights into the epidemiology and natural history of HPV and cervical cancer. Current recommendations are based, by necessity, on cytology alone, and will be limited in generalizability to evolving screening strategies with co-testing and primary HPV testing. The lack of empirical data to define what constitutes 'adequate recent screening with negative results' is compounded by difficulties in predicting future risk without consideration of concepts of HPV latency and cohort effects of changing sexual behaviour in US women over time. We urge caution in extrapolating past risk experience in post-menopausal women to today's population, and suggest study designs to strengthen the evidence base in well-screened older women. We further recommend building the qualitative evidence base to better define the harms and benefits of screening among older women. Extending the lifetime of screening is a matter of finding the appropriate balance of benefits of cancer reduction and limitation of harms and costs of 'overscreening'. This will require moving beyond current emphasis on number of colposcopies as the metric of harm. Our commentary is meant to stimulate intellectual debate regarding the certainty of our existing knowledge base and set clear research priorities for the future.

Modeling of US Human Papillomavirus (HPV) Seroprevalence by Age and Sexual Behavior Indicates an Increasing Trend of HPV Infection Following the Sexual Revolution.

Background: The United States has experienced an increase in the incidence of human papillomavirus (HPV)-related cancers that are not screen-detectable. It has been hypothesized, but not directly demonstrated, that this is due to increasing HPV prevalence in the unvaccinated population. Methods: Female self-reported numbers of lifetime sex partners and HPV serology from the National Health and Nutrition Examination Survey (NHANES) were used to develop mathematical models of sexual partner acquisition and antibody dynamics. Modeled trends in sexual behaviors were compared to incidence data for cervical adenocarcinoma, oropharyngeal cancer, and anal cancer. Results: The age-specific HPV seroprevalence data were best explained by a partner acquisition model that explicitly accounted for cohort-dependent changes in sexual behavior. Estimates of the mean time to loss of natural antibodies varied by model, ranging from 49 to 145 years. Inferred trends in sexual behavior over the past decades paralleled the increasing incidence of HPV-related cancers in the United States. Conclusions: The findings suggest that lower HPV seroprevalence in older US women primarily reflects cohort-specific differences in sexual behaviors, and is only marginally attributable to immune waning with age. Our results emphasize the importance of continuing surveillance of sexual behaviors, alongside vaccine status, to predict future disease burden.

Concordance of Penile and Oral Human Papillomavirus Infections Among Men in the United States.

This study examined the concordance of penile and oral human papillomavirus (HPV) infections in the United States. A total of 1683 men aged 18-59 years who participated in the 2013-2014 National Health and Nutrition Examination Survey and had results of oral and penile HPV DNA testing were examined. The prevalence of any HPV genotype was 45.3% on the penis, 11.2% in the oral cavity, and 8.8% at both sites. The prevalence of HPV in the oral cavity was higher among those with than among those without penile HPV infection (19.3% vs 4.4%; prevalence ratio, 4.37 [95% confidence interval, 2.66-7.16]). The prevalence of ≥1 genotype-concordant HPV infection was 3.2% and was associated with sexual behavior, independent of demographic characteristics and smoking status. Sexual behavior may partly explain the observed association between penile and oral HPV infections.