Acceptability and Concordance of Self- Versus Clinician- Sampling for HPV Testing among Rural South Indian Women

Background: Despite being largely preventable, HPV-related cervical cancers continues to be the second highest cause of cancer deaths among Indian women. HPV testing using self-sampled samples may offer an opportunity to expand cervical cancer screening in India where there is currently a shortage of providers and facilities for cervical cancer screening. The study examines acceptability and concordance of self vs. clinician collected samples for HPV-relted cervical cancer screening among rural South Indian women. Methods: Between May and August 2017, eight mobile screening clinics were conducted among 120 eligible women in rural villages in Mysore District, India. Women over the age of 30 underwent informed consent process and then self-sampled a sample for cervicovaginal HPV DNA testing. Next, the women underwent clinical exam where the clinician collected a cervicovaginal HPV DNA sample. Following the clinical exam, all participants answered an interviewer-administered questionnaire to assess their history of cervical cancer screening and acceptability of self- and clinician-sampling methods. To assess diagnostic accuracy, concordance of self- and clinician-sampled HPV DNA specimens was calculated in addition to five measures of acceptability (feeling of caring, privacy, embarrassment, genital discomfort, and genital pain). Results: Study participants had a median age 39 years, about four-in-ten (41.7%) had a secondary education or above, the vast majority (87.5%) were married and only 3.4% reported having screened for cervical cancer. For all measures of participant acceptability, self-sampling was rated significantly higher than clinician-sampling. Cohen’s kappa was 0.73 (95% CI: 0.34, 1.00), indicating substantial agreement between self- and clinician-sampling. Conclusion: This study demonstrates that HPV self-sampling for cervical cancer screening is feasible and acceptable in a community setting among South Indian rural women. Concordance between self-sampling and clinician-sampling was adequate for screening in community settings.     

新疆维吾尔族妇女宫颈癌筛查方法横断面比较研究

[目的]探讨适合新疆维吾尔族妇女宫颈癌的筛查方法。[方法]于2006～2007年采用整群抽样方法,选择新疆维吾尔族妇女883名,采用自我采样HPV检测,液基细胞学检查,医生采样HPV检测,肉眼筛查(VIA)进行宫颈癌筛查。分析和比较不同筛查方法的灵敏度、特异度、阳性预测值、阴性预测值。[结果]医师采样HPV检测的灵敏度和特异度均为最高(P<0.01),自我采样的灵敏度与细胞学检查相似(P>0.05),但自我采样HPV检测的特异度高于细胞学检查(P<0.01),与医生采样HPV检测相似(P>0.05)。肉眼筛查的灵敏度和特异度为最低。[结论]新疆维吾尔族妇女的宫颈癌筛查方案应首选医生采样HPV检测,自我采样HPV检测是比较适合于新疆民族地区妇女的方案,在偏远和缺少设备的地区,肉眼筛查也是一种可行的筛查方法。     

Acceptability and Preference for Human Papilloma Virus Self-Sampling among Thai Women Attending National Cancer Institute

Background: Cervical cancer screening is an important public health strategy to reduce cervical cancer incidence and mortality. Human papillomavirus (HPV) self-sampling is the alternative method that can potentially increase participation in cervical cancer screening. This study aimed to evaluate the acceptability of HPV self-sampling as a primary cervical cancer screening among Thai women. Methods: A cross-sectional study was conducted at National Cancer Institute, Thailand, between March and September 2021. Eligible women were invited to collect their own samples with a vaginal cotton swab for cervical screening. The data on demographics, acceptability, and preference for HPV self-sampling were collected via a self-administered questionnaire. A Likert scale was used to assess the response of self-sampling acceptability. The multivariable logistic regression determined factors that influence preference for HPV self-sampling. Results: A total of 265 participants were recruited. Over 70% agreed that self-sampling was easy, less embarrassing, and not painful. They also felt confident in their ability to self-sample correctly and would recommend this method to a friend or relative. For their next screening round, 66.4% preferred self-sampling whereas 33.6% preferred clinician-collected samples as routine screening. The factors that influence preference for self-sampling were age, marital status, feeling less embarrassed, and confidence in performing the tests. Conclusions: Most of the study participants accepted HPV self-sampling. This suggests that the self-sampling method will be an additional option to increase cervical cancer screening coverage which leads to improving the effectiveness of the national program.     

Cervical Cancer Screening: Recommendations for Muslim Societies

Background: The overall cervical cancer incidence rate is low in Iran; however, because of a higher risk of death for cervical cancer, a disease that kills women in middle age, a cervical cancer control program is needed. The aim of this study was to provide consensus recommendation for cervical cancer prevention in Iran and other Muslim societies with low incidences of cervical cancer. Materials and Methods: Through a practical guideline development cycle, we developed six questions that were relevant to produce the recommendation. We reviewed 190 full text records of cervical cancer in Iran (1971 to 2013) of which 13 articles were related to the data needed to answer the recommendation questions. We also reviewed World Health Organization, IARC, GLOBOCAN report, Iran Ministry of Health cancer registry report and 8 available foreign countries guidelines. Lastly, we also evaluated the Pap smear results of 825 women who participated in the Iranian HPV survey, of whom 328 were followed-up after a 5-year interval. Results: The obtained data highlighted the burden of HPV and cervical cancer situation in Iran. Experts emphasized the necessity of a cervical cancer screening program for Iranian women, and recommended an organized screening program with a cytological evaluation (Pap smear) that would start at the age of 30 years, repeated every 5 years, and end at the age of 69 years. Meanwhile, there is no need for screening among women with a hysterectomy, and screening should be postponed to post-partum among pregnant women. Conclusions: An organized cervical cancer screening is a necessity for Iran as more than 500-900 women in middle age diagnosed with an invasive cervical cancer every year cannot be ignored. This recommendation should be taken into account by the National Health System of Iran and Muslim countries with shared culture and behavior patterns. CUBA HPV test could be consideration in countries Muslim country with appropriate budget, resources and facility.     

HPV self-sampling as an alternative strategy in non-attenders for cervical screening - a randomised controlled trial

Background:

A randomised trial to ascertain whether women who do not attend for cervical screening are more likely to respond to the opportunity to collect a self-sample for human papillomavirus (HPV) testing, or to a further invitation to attend for cervical screening.

Methods:

The study was carried out in a Primary Care Trust (PCT) in London between June 2009 and December 2009. In total, 3000 women were randomly selected from persistent non-responders (i.e., who had not responded to at least two invitations to attend for screening). The women were randomised on a 1 : 1 basis to either receive an HPV self-sampling kit or a further invitation to attend for cervical cytology. The main outcome measures were (1) percentage of women attending for cervical cytology compared with those returning a self-sample HPV test or attending for cytology subsequent to receiving the kit and (2) percentage of those testing positive for HPV who attended further investigation.

Results:

The total response in the self-sampling group for screening was 10.2%. Of the 1500 women in the control group sent a further invitation for cervical screening, 4.5% attended for cytology screening. This difference is highly statistically significant (P<0.0001). Of the 8 women who tested positive for HPV, 7 attended for a cervical smear and had a concurrent colposcopy. Three of these (43%) had high-grade disease (defined as CIN 2+), with one found to have an invasive cancer (stage 1b) and one CIN 3.

Conclusions:

The value of this intervention relies on the detection of high-grade CIN and early stage cancer with a good prognosis. The relatively high yield of abnormalities found is consistent with that expected among a hard to reach and relatively high-risk group of women. Our study suggests that self-sampling could increase participation among non-responders in England, but further work is needed to ascertain whether the low response rate seen here is likely to be representative of the rest of the country. Other studies are needed to investigate the response to self-sampling in different demographic and geographic settings.     

Results of Self-Sampling Methodology Impression for Cervical Cancer Screening in Mongolia

Objective:  Mongolia is a sparsely populated country; however, almost fifty percent of the population lives in the capital city. Medical care services and exceptionally well-organized cervical cancer screening tests are limited in remote areas. To improve cervical cancer screening test coverage, we compared the interest between physicians taking samples and self-sampling among the attendees in this study. Methods: A total of 175 women participated in this study. The hundred twelve women visited the Gynecology ward, and the sixty-three women were provided with the cervical self-sampling test kit and filled out a questionnaire. Subsequently, the acceptability of physician taking and self-sampling were evaluated using a questionnaire. All specimens were processed using the TACAS LBC system, and the quality of samples was tested by cytology. Results: Regarding the acceptability of self-sampling, the selections for subsequent screening were 36% self-sampling and 64% gynecologist-sampling methods. The acceptability rates were higher in the remote areas than the urban areas. However, 64% of the participants lacked knowledge that the causative agent of cervical cancer is the human papillomavirus, and 66.9% mainly were sexually transmitted. In addition, 82.3% of the women surveyed were unaware that there was a vaccine to prevent cervical cancer, but 88.6% wanted to be vaccinated. Of most women, 44.4% chose self-sampling due to no embarrassment in the gynecological examination. The self-sampling preferences were dominant in the old age group (61.6%). The cytology satisfaction rate in physician-sampling (99.1%) was higher than in the self-sampling group (69.8%). Conclusion: The Implementation of the self-sampling tool may be considered a primary screening. The self-sampling test can adopt into the early screening program and may increase the coverage of the screening program and improve the quality.     

Comparative performance evaluation of different HPV tests and triaging strategies using self-samples and feasibility assessment of thermal ablation in ‘colposcopy and treat’ approach: A population-based study in rural China

Human papillomavirus (HPV) test, self-sampling and thermal ablation for cervical intraepithelial neoplasia (CIN) have been developed separately to increase screening coverage and treatment compliance of cervical cancer screening programmes. A large-scale study in rural China screened 9,526 women with their combinations to explore the optimal cervical cancer-screening cascade in the real-world. Participants received careHPV and polymerase chain reaction (PCR) HPV tests on self-collected samples. Women positive on either HPV test underwent colposcopy, biopsy and thermal ablation in a single visit. Samples positive on either HPV test were retested for genotyping. Absolute and relative performance of HPV tests, triage strategies, ‘colposcopy and thermal ablation’ approach were statistically evaluated. PCR HPV test detected 33.3% more CIN grade two or worse (CIN2+) at a cost of 28.1% more colposcopies compared to careHPV. Sensitivities of PCR HPV and careHPV tests to detect CIN2+ were 96.7 and 72.5%. Specificities for the same disease outcome were 82.1 and 86.0%. Triaging HPV-positive women with HPV16/18 genotyping considerably improved the positive predictive value for CIN2+ (4.8–5.0 to 18.2–19.2%). Ninety-six women positive on HPV and having abnormal colposcopy were eligible for thermal ablation and all accepted same-day treatment, contributing to 64.6% being treated appropriately (CIN1+ on histopathology), which reached up to 84.8% among women positive on HPV 16/18 triage. No serious side-effects/complications were reported. The combination of PCR HPV test followed by HPV 16/18 triaging on self-collected samples and colposcopy of triage positive women followed by immediate thermal ablation might be the appropriate screening cascade for rural China.     

Widening the offer of human papillomavirus self-sampling to all women eligible for cervical screening: Make haste slowly

Self-collection of samples for human papillomavirus (HPV) testing has the potential to increase the uptake of cervical screening among underscreened women and will likely form a crucial part of the WHO's strategy to eliminate cervical cancer by 2030. In high-income countries with long-standing, organised cervical screening programmes, self-collection is increasingly becoming available as a routine offer for women regardless of their screening histories, including under- and well-screened women. For these contexts, a validated microsimulation model determined that adding self-collection to clinician collection is likely to be cost-effective on the condition that it meets specific thresholds relating to (1) uptake and (2) sensitivity for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We used these thresholds to review the ‘early-adopter’ programme-level evidence with a mind to determine how well and how consistently they were being met. The available evidence suggested some risk to overall programme performance in the situation where low uptake among underscreened women was accompanied by a high rate of substituting clinician sampling with self-collection among well-screened women. Risk was further compounded in a situation where the slightly reduced sensitivity of self-sampling vs clinician sampling for the detection of CIN2+ was accompanied with lack of adherence to a follow-up triage test that required a clinician sample. To support real-world programmes on their pathways toward implementation and to avoid HPV self-collection being introduced as a screening measure in good faith but with counterproductive consequences, we conclude by identifying a range of mitigations and areas worthy of research prioritisation.     

A randomized trial of mailed HPV self-sampling for cervical cancer screening among ethnic minority women in South Florida

Purpose

HPV self-sampling has previously been shown to increase cervical cancer screening among ethnic minority and immigrant women. We conducted a randomized pragmatic trial to examine the effectiveness of HPV self-sampling delivered via in-person versus by US mail for medically underserved Hispanic, Haitian, and non-Hispanic Black women living in South Florida.

Methods

We randomized women aged 30–65 who had not completed Pap smear screening in the past 3 years into two groups: (1) HPV self-sampling delivered in-person (IP) by a community health worker (CHW; IP?+?SS) or (2) HPV self-sampling delivered via US mail (SS?+?Mail). Our primary outcome was HPV self-sampling completion by 6-month post-study enrollment.

Results

We enrolled 600 women. Approximately 65% were Hispanic and 35% were Haitian or non-Hispanic Black. Nearly half (43%) had an income of less than $20,000/year and 67% were uninsured. In intent-to-treat analyses, 71.6% of participants in the SS?+?Mail group and 81.0% of participants in the IP?+?SS group completed HPV self-sampling.

Conclusion

Mailed HPV self-sampling is an effective strategy to increase cervical cancer screening among underserved immigrant and ethnic minority women.

     

Short-time repeat high-risk HPV testing by self-sampling for screening of cervical cancer

Background:

Testing for high-risk human papillomavirus (HPV) in primary screening for cervical cancer is considered more sensitive, but less specific, in comparison with Pap-smear cytology. Women with persistent HPV infections have a higher risk of developing cervical intraepithelial neoplasia 2+ (CIN2+) lesions. This study was performed to evaluate the gain in specificity for detection of histologically confirmed CIN2+ lesions achieved by short-time repeat testing for high-risk HPV in women aged 30–65 years, with the primary sample for HPV analysis taken by self-sampling.

Methods:

A total of 8000 women in Uppsala County, aged 30–65 years, who had not attended organised screening for 6 years or longer, were offered self-sampling of vaginal fluid at home and the samples sent for HPV typing. Of these, 8% (669) were not possible to contact or had performed hysterectomy. Women positive for high-risk HPV in the self-sampling test were invited for a follow-up HPV test and a cervical biopsy on average 3 months after the initial HPV test.

Results:

In all, 39% (2850/7331) of invited women chose to perform self-sampling of vaginal fluid at home. High-risk HPV infection was found in 6.6% (188) of the women. In all, 89% of the women testing HPV positive performed a follow-up examination, on average 2.7 months, after the first test and 59% of these women were HPV positive in the follow-up test. The prevalence of CIN2+ lesions in women with an initial HPV-positive test was 23% (95% CI 18–30%) and in women with two consecutive HPV-positive tests was 41% (95% CI 31–51%). In women with two positive HPV tests, the prevalence of CIN2+ lesions varied from 49% in women at age 30–39 years to 24% in women at age 50–65 years. Short-time repeat HPV testing increased the specificity for detection of CIN2+ lesions from about 94.2% to 97.8%. The most prevalent HPV types were HPV16 (32%), followed by HPV18/45 (19%) and HPV 33/52/58 (19%).

Conclusion:

The short-time persistence of high-risk HPV infection in this age group was about 60%. Repeat testing for high-risk HPV using self-sampling of vaginal fluid can be used to increase the specificity in the screening for cervical cancer in women aged 30–65 years.     

A systematic review of the role of human papilloma virus (HPV) testing within a cervical screening programme: summary and conclusions

A systematic review of the available evidence on the role of HPV testing in cervical screening has been published by the Health Technology Assessment Committee of the UK Department of Health. The review summarized relevant data on testing methods, natural history, and prevalence of the virus in different disease groups. Cost-effectiveness modelling was undertaken. Ten major conclusions were reached and are reported here. The key conclusions were that HPV testing was more sensitive than cytology, but that there were concerns about specificity, especially in young women. The increased sensitivity led to a recommendation that HPV testing be introduced on a pilot basis for women with borderline and mild smears. HPV testing has great potential as a primary screening test, but large trials are needed to properly evaluate this application and to determine if its introduction can reduce invasive cancer rates. There is an urgent need to undertake a large trial of HPV testing in conjunction with other new technologies (liquid-based cytology and computer-assisted cytology reading) to determine the best way to integrate them into ongoing screening programmes. A range of issues including the age to start and stop screening, the appropriate screening interval, the role of self-sampling for HPV testing and the choice of primary test (HPV and/or cytology) require further evaluation.     

Primary cervical cancer screening by self-sampling of human papillomavirus DNA in internal medicine outpatient clinics.

BACKGROUND: We determined whether testing of self-collected vaginal swabs for human papillomavirus (HPV) DNA can be used to screen for cervical disease within internal medicine outpatient clinics. PATIENTS AND METHODS: In this prospective study, 560 patients visiting two referral outpatient clinics for internal medicine were asked to take an HPV self-sample. Acceptability of self sampling, HPV prevalence and cervical intraepithelial neoplasia (CIN) detection rate were evaluated. RESULTS: 435 women (78%) performed HPV self-sampling; 1.5% considered self-sampling to be difficult. 134 women (31%) tested positive for high-risk type of HPV. There were significant differences between HPV-positive and -negative women with respect to the following: mean age (42 versus 46 years), number of women aged <16 years at first coitus (35% versus 23%) and history of drug abuse (8.3% versus 2.6%). Colposcopy could be performed for 70 HPV positive women: CIN 1-3 was identified in 24%. Two of 52 women with HPV-negative results undergoing colposcopy had biopsy-confirmed CIN 1. Test performance for detection of CIN 2-3 after correction for verification bias: sensitivity, 100%; specificity, 71%; negative predictive value, 100%; positive predictive value, 10%. HPV persistence was associated with a 5.7-fold risk of CIN 2-3 detection at follow-up. CONCLUSIONS: Self-assessment for HPV DNA is an easy, feasible and well-accepted method for HPV testing and for cervical cancer screening in internal medicine outpatient clinics.     

Community-Based Prevalence of Genital Human Papilloma Virus (HPV) Infection: a Systematic Review and Meta-Analysis

Introduction: Cervical cancer probably represents the best-studied human cancer caused by a viral infection and the causal association of this preventable cancer with human papilloma virus (HPV) is well established. Worldwide there is a scarcity of data regarding HPV prevalence with vast differences existing among populations. Objective: The aim of this meta-analysis was to determine the community-based HPV prevalence estimates among asymptomatic women from urban and rural set ups and in participants of cancer screening clinics. Study design: Systematic review and meta-analysis. Methods: PubMed-Medline, CINAHL, Scopus, and Google scholar were systematically searched for studies providing prevalence data for HPV infection among asymptomatic women between 1986 and 2016. Results: The final analysis included 32 studies comprising a population of 224,320 asymptomatic women. The overall pooled HPV prevalence was 11% (95% confidence interval (CI), 9%-12%). The pooled HPV prevalence of 11% (95% CI, 9%-11%) was observed among women attending cervical cancer screening clinics. The pooled HPV prevalences were 10% (95% CI 8%-12%) and 11% (95% CI 4%-18%) from urban and rural areas respectively, indicating higher infection rates among the rural women with the least access to cancer screening and cancer care. Conclusion: The prevalence rates in this systematic quantitative review provide a reliable estimate of the burden of HPV infection among asymptomatic women from developed as well as developing nations. Rural women and women attending cervical cancer screening programmes feature higher genital HPV prevalences compared to their urban counterparts.     

Self-Collection Tools for Routine Cervical Cancer Screening: A Review

Sub-optimal participation is a major problem with cervical cancer screening in developing countries whichhave no organized national screening program. There are various notable factors such as ‘embarrassment’,‘discomfort’ and ‘no time’ cited by women as they are often also the bread winners for the family. Implementationof self-sampling methods may increase their participation. The aim of this article was to provide a survey ofvarious types of self-sampling tools which are commonly used in collection of cervical cells. We reviewed currentlyavailable self-sampling devices and collated the advantages and disadvantages of each in terms of its acceptanceand its accuracy in giving desired results. In general, regardless of which device is used, self-sampling for cervicalscrapings is highly acceptable to women in most of the studies cited.     

Women’s Knowledge,Attitude and Practice on Cervical Cancer and Its Screening in Dhaka,Bangladesh

Background: Cervical cancer is the fourth most common cancer among women in the world. Visual Inspection with Acetic Acid (VIA) is a common screening test for cervical cancer in Bangladesh. This study will assess the knowledge, attitude and practice towards cervical cancer and screening among women residing in Dhaka district. Methods: A cross-sectional survey was conducted among 956 women aged 30 years and above in Dhaka. The women’s score on knowledge, attitude and practice were categorized as sufficient or insufficient. We calculated frequencies and used binary logistic regression to describe and assess the association between scores and socio-demographic characteristics of respondents. Results: Most (87%) respondent knew about cervical cancer and 13% knew that HPV is a risk factor for cervical cancer. Women who had sufficient knowledge were more likely to test VIA than those who had insufficient knowledge (39%, OR: 2.5; CI: 1.6, 2.8). Most (92%) would advise other women to have a VIA test. However, only 26% had a VIA test and 2% were vaccinated in private health care facilities for Human Papilloma Virus (HPV). Women who had sufficient attitude were equally likely to test VIA than those who had insufficient attitude. The VIA was underutilized because of low privacy during examination, unaware that VIA screened for cervical cancer, belief that they must pay for the test, and nurses performed examination. Conclusion: Women were knowledgeable about cervical cancer and likely to have a VIA test. However, the VIA test in underutilized and HPV vaccine coverage was low.     

Comparative Assessment of a Self-sampling Device and Gynecologist Sampling for Cytology and HPV DNA Detection in a Rural and Low Resource Setting: Malaysian Experience

Purpose: This study was conducted to assess the agreement and differences between cervical self-sampling with a Kato device (KSSD) and gynecologist sampling for Pap cytology and human papillomavirus DNA (HPV DNA) detection. Materials and Methods: Women underwent self-sampling followed by gynecologist sampling during screening at two primary health clinics. Pap cytology of cervical specimens was evaluated for specimen adequacy, presence of endocervical cells or transformation zone cells and cytological interpretation for cells abnormalities. Cervical specimens were also extracted and tested for HPV DNA detection. Positive HPV smears underwent gene sequencing and HPV genotyping by referring to the online NCBI gene bank. Results were compared between samplings by Kappa agreement and McNemar test. Results: For Pap specimen adequacy, KSSD showed 100% agreement with gynecologist sampling but had only 32.3% agreement for presence of endocervical cells. Both sampling showed 100% agreement with only 1 case detected HSIL favouring CIN2 for cytology result. HPV DNA detection showed 86.2%agreement (K=0.64, 95% CI 0.524-0.756, p=0.001) between samplings. KSSD and gynaecologist sampling identified high risk HPV in 17.3% and 23.9% respectively (p= 0.014). Conclusion: The self-sampling using Kato device can serve as a tool in Pap cytology and HPV DNA detection in low resource settings in Malaysia. Self-sampling devices such as KSSD can be used as an alternative technique to gynaecologist sampling for cervical cancer screening among rural populations in Malaysia.     

Baseline cytology,human papillomavirus testing,and risk for cervical neoplasia: a 10-year cohort analysis

BACKGROUND: Annual Pap smear screening has been favored over less frequent screening in the United States to minimize the risk of cervical cancer. We evaluated whether simultaneous screening with a Pap test and human papillomavirus (HPV) testing is useful for assessing the risk for cervical intraepithelial neoplasia (CIN) 3 or cervical cancer. METHODS: We enrolled 23 702 subjects in a study of HPV infection at Kaiser Permanente, Northwest Division, Portland, OR. Data were analyzed for 20 810 volunteers who were at least 16 years old (mean = 35.9 years) with satisfactory baseline Pap tests and suitable samples for HPV testing. Women were followed for up to 122 months (from April 1, 1989, to June 30, 1999) to determine the risk for histopathologically confirmed CIN3 or cancer. RESULTS: Among 171 women with CIN3 or cancer diagnosed over 122 months, 123 (71.9%, 95% confidence interval [CI] = 65.2% to 78.7%) had baseline Pap results of atypical squamous cells or worse and/or a positive HPV test, including 102 (86.4%, 95% CI = 80.3% to 92.6%) of the 118 cases diagnosed within the first 45 months of follow-up. During this 45-month period, the cumulative incidence of CIN3 or cancer was 4.54% (95% CI = 3.61% to 5.46%) among women with a Pap test result of atypical squamous cells or worse, positive HPV tests, or both compared with 0.16% (95% CI = 0.08% to 0.24%) among women with negative Pap and HPV tests. Age, screening behavior, a history of cervical cancer precursors, and a history of treatment for CIN minimally affected results. CONCLUSIONS: Negative baseline Pap and HPV tests were associated with a low risk for CIN3 or cancer in the subsequent 45 months, largely because a negative HPV test was associated with a decreased risk of cervical neoplasia. Negative combined test results should provide added reassurance for lengthening the screening interval among low-risk women, whereas positive results identify a relatively small subgroup that requires more frequent surveillance.