Examining Attitudes Toward HPV Self-Collection Among Clinicians Practicing in Federally Qualified Health Centers Using the Cabana Guideline Based Practice Improvement Framework

Background: Control of cervical cancer in developing countries has been hampered by a failure to achieve high screening uptake. HPV self-collection could increase screening coverage, but implementation of this technology is difficult in countries with low-income settings. In Argentina, during 2012-2014 we implemented the Jujuy Demonstration (JDP) to introduce HPV testing as primary screening. As part of the JDP, we investigated whether offering HPV self-collection during routine home visits by community health workers could increase cervical screening. Methods: We describe the programmatic components developed for each phase of HPV self-collection implementation as well as present data about its performance to detect CIN2+ lesions. For that we analyzed data from the national screening information system (SITAM); we reviewed program documents, presentations, and reports; and we also analyzed qualitative/quantitative data about HPV self-collection acceptability by women and health providers. Results: Acceptability and effectiveness of HPV self-collection to increase screening-uptake was evaluated in a research project (The EMA Project) carried out in 2012 in the province of Jujuy. The project combined qualitative research with a Cluster Randomized Trial. 200 community health workers were randomly allocated in a 1:1 ratio to either the intervention group (offered women the chance to self-collect a sample for cervical screening during a home visit) or the control group (advised women to attend a health clinic for cervical screening). Results showed that HPV-self collection was accepted by women and health providers, and effective to increase screening uptake (risk ratio 4·02, 95% CI 3·44–4·71). HPV-testing CIN2+ detection rate was 1.15%. Results from the EMA Project were used to design and develop key components of the scaling-up phase (training and communication materials, protocols, and guidelines). In 2014 HPV self-collection was extended to the whole province as a strategy to increase screening among socially vulnerable women. It was offered by 70% of the 700 provincial community health workers. Facilitators of self-collection scaling-up were the organizational capacity of the provincial health system, sustainable funding for HPV testing, and local consensus about the value of the technology. In 2014, self-collection represented 38% of total HPV testing and, if we consider the whole JDP, 10% of screening in the target population was achieved through self-collection. CIN2+ detection rate of HPV self-collection when used as a programmatic strategy was 0.6%; this decrease in relation to the detection rate found in the EMA Project is probably explained by a loss to follow-up. Conclusion: HPV self-collection was successfully scaled up, with a high level of adoption among health providers, which resulted in increased screening among socially vulnerable underscreened women. Citation Format: Silvina Arrossi. Introduction of HPV self-collection in Argentina, main results, and lessons [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr IA13.

Acceptability of HPV self-collection: A qualitative study of Black women living with type II diabetes and social vulnerability

Self-collection for HPV testing among emergency department patients: A prospective, interventional, single-arm, feasibility study.

Primary HPV testing: U.S. women's awareness and acceptance of an emerging screening modality

PURPOSE Tanzania ranks fifth in cervical cancer disease burden globally, with 9,772 new cases and 6,695 deaths reported each year. In the newest version of Tanzania's national cervical cancer strategy, the Ministry of Health recommends that HPV DNA testing is integrated with the national cervical cancer prevention program, to align with the WHO screening recommendations. Recruitment to screening programs remains a challenge in low- and middle-income countries, and there is little evidence to inform recruitment strategies that might improve attendance rates, especially in Tanzania. Results from a systematic review of strategies to improve health and medical research suggest that involving community groups in the research process and ensuring that content and delivery of the intervention is socially acceptable, can improve the likelihood of uptake. The ‘Dada’ study will be conducted, as part of the national cervical cancer prevention program. METHODS The study aims to recruit 1,500 women (age 25-49 if HIV+ or 30-49 if HIV status unknown) in the Kilimanjaro region to evaluate a hybrid-2 evaluation of intervention and implementation effectiveness (e.g., acceptability, feasibility, and fidelity) with cluster randomization of communities to two arms, each testing a different method of recruitment: A) individual, opportunistic recruitment in public settings and B) recruitment through structured community meetings. Recruitment will be performed by community healthcare workers from 30 communities using the two strategies. In both arms, an educational video (‘Dada’) will be delivered to women to encourage HPV self-collection. RESULTS To compare individual and group recruitment strategies in terms of HPV self-collection uptake. This will be examined through various demographic factors, such as age, marital status, education, income, insurance, previous cervical cancer screening, and geographic location (rural, semi-rural or urban). CONCLUSION There is a critical need to generate further evidence for implementation of effective and sustainable strategies to optimize cervical cancer screening and increase the number of women that receive HPV self-collection. The results of our study will also generate informed evidence regarding the optimized strategy to improve the cervical screen-triage-treat approach in Tanzania. The knowledge gained will be disseminated to other African countries with a similar cancer-health disparity.

BackgroundLittle is known about cervical cancer screening strategy utilization (cytology alone, cytology plus high-risk human papillomavirus [HPV] testing [cotesting], primary HPV testing) and test results in the United States. MethodsData from the Centers for Disease Control and Prevention's National Breast and Cervical Cancer Early Detection Program were analyzed for 199,578 persons aged 21–65 years screened from 2019 to 2020. Screening test utilization and results were stratified by demographic characteristics and geographic region. Age-standardized pooled HPV test positivity and genotyping test positivity were estimated within cytology result categories. ResultsPrimary HPV testing was performed in 592 persons (0.3%). Among the remaining 176,290 persons aged 30–65 years, cotesting was utilized in 72.1% (95% confidence interval [CI] 71.9–72.3%), and cytology alone was utilized in 27.9% (95% CI 27.7–28.1%). Utilization of cytology alone varied by geographic region, ranging from 18.3% (95% CI 17.4–19.1%) to 49.0% (95% CI 48.4–49.6%). HPV genotyping test utilization among those with positive pooled HPV test results was 33.9%. In persons aged ≥30 years, variations in age-adjusted test results by region were observed for pooled HPV-positive test results and for HPV genotyping-positive test results. ConclusionsCervical cancer screening strategy utilization and test results vary substantially by geographic region within a national screening program. Variation in utilization may be due to regional differences in screening test availability or the preferences of healthcare systems, screened persons and/or clinicians. Test result variations may reflect differing risk factors for HPV infections by geographic region.

BackgroundMounting evidence affirms HPV testing as an effective cervical cancer screening tool, and many organized screening programs are considering adopting it as primary testing. HPV self-collection has comparable sensitivity to clinician collected specimens and is considered a feasible option in hard-to-reach women. We explored women’s intentions to HPV self-collect for cervical cancer screening from a cohort participating in a Canadian randomized controlled cervical cancer screening trial.MethodsWomen aged 25–65 were invited to complete an online survey assessing intentions to be screened with HPV testing instead of the Pap smear. The survey was based in the Theory of Planned Behaviour and questions were included to assess women’s intentions to self-collect for HPV. Demographic characteristics of women who intended to self-collect were compared with those who did not. Demographic and scale variables achieving a p-value <0.1 in the univariate and bivariate analyses were included in the stepwise logistic regression model. The final model was created to predict factors associated with women’s intentions to self-collect an HPV specimen for cervical cancer. Odds ratios were calculated with 95% confidence intervals to identify variables associated with a woman’s intention to self-collect for cervical cancer screening.ResultsThe overall survey response rate was 63.8% (981/1538) with 447 (45.6%) reporting they intended to self-collect, versus 534 (54.4%) reporting they did not. In the univariate analysis, women with more than high school education were more likely to self-collect. Women who intended to receive HPV testing versus the Pap smear were 1.94 times as likely to be in favour of self-collection and those who intended to self-collect had significantly higher attitudinal scores towards HPV self-collection. The adjusted odds ratio and 95% confidence interval from the multivariate analysis demonstrated attitude towards self-collection was the only significant variable predicting a woman’s intention to self-collect (OR 1.25; 95% CI: 1.22, 1.29).ConclusionsThe primary predictor of a woman’s intention to HPV self-collect for cervical cancer screening was her attitude towards the procedure. From a program planning perspective, these results indicate that education and awareness may be significant contributing factors to improving acceptance of self-collection and subsequently, improving screening attendance rates.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2458-14-1060) contains supplementary material, which is available to authorized users.

Background The American Cancer Society’s 2020 guidelines recommend cervical cancer screening for individuals with a cervix aged 25-65 every five years with an HPV test. However, cervical cancer disproportionately affects under-screened populations, including migrant workers, immigrants, and underserved communities. In Oregon, these groups face language, cultural, and healthcare access barriers. To address these challenges, HPV screening must be accessible and culturally sensitive. In May 2024, the FDA approved HPV self-collection using the Cobas HPV Test (Roche Molecular Systems) in healthcare settings. This study aims to evaluate the effectiveness and accessibility of HPV self-collection for underserved communities. Methods This study, approved by the Institutional Review Board at Oregon Health &amp; Science University (OHSU), partnered with the Chinese Friendship Association of Portland (CFAP) to recruit women aged 25-65. Self-collection took place at CFAP’s free clinic, where pathologists guided participants through the process. Participants used Copan swabs (Copan Diagnostics, Murrieta, CA) for vaginal sample collection, which were transferred to ThinPrep media (Hologic, Marlborough, MA) for HPV testing using the Cobas 8800 system (Roche Diagnostics, Pleasanton, CA). Participants also completed questionnaires to provide feedback on the screening process. Results Twenty-eight Asian women, aged 28-62 (mean age 48.3), participated. The group included 1 Vietnamese, 3 from Myanmar, and the rest were Chinese. All self-collection samples were valid; 26 were negative for HPV, and 2 were positive for non-16/18 HPV types. Follow-up Pap smears revealed one normal result and one with atypical squamous cells of undetermined significance. A colposcopy confirmed cervical intraepithelial neoplasia grade 1 in one case, with follow-up recommended in one year. Seventeen participants completed the post-event survey. Four (23.5%) had received the HPV vaccine, and 3 were vaccinated at ages 20–21. When asked about their preference for self-collection, 64.7% of participants were very likely to choose it again, while 29.4% were likely to choose it. Only 5.9% were neutral. Regarding ease of use, 58.8% found the kit very easy, and 29.4% found it easy. Only 5.9% found it difficult. Forty-seven percent found the instructions very clear, while 35.3% felt they were clear. When asked if they would recommend the self-collection method, 58.8% were very likely to recommend it, and 29.4% were likely to recommend it. Feedback from the events was positive, with 41.2% appreciating the convenience and 29.4% praising the friendly, caring staff. Furthermore, 70.6% stated they would not have been able to access screening without the event, highlighting the importance of community-based initiatives. Conclusion This study demonstrates that HPV self-collection is an effective and accessible method for cervical cancer screening, particularly for underserved populations. The high preference for self-collection, positive feedback on ease of use and clarity, and the increased accessibility underscore its potential to improve early detection and reduce cervical cancer incidence in under-screened communities. Additionally, pathologists and laboratory staff play a critical role in leading outreach efforts that not only enhance access to screening but also reduce the overall cost of cervical cancer screening when compared to traditional co-testing and cytology-only methods.

Cervical cancer screening has been shifting from primary cytology to primary HPV testing worldwide as primary HPV testing is more sensitive than primary cytology. To the best of our knowledge, the current study is the first in Japan to examine the feasibility of primary HPV testing. One of the disadvantages of this shift is that hrHPV-/≥LSIL/CIN2+ (high-risk HPV negative cancers or pre-cancerous lesions with abnormal cytology results) can be missed. The objectives of the present study are to clarify in detail CIN2+ missed by this shift and to evaluate the feasibility of primary HPV testing in Japan. Data from 115,273 women who underwent co-testing with cytology and HPV testing in cancer screening were used in the current study. The cases with hrHPV-/≥LSIL (‘hrHPV-/≥L-SIL’ include CIN2-, in contrast, ‘hrHPV-/≥L-SIL/CIN2+’ doesn't include CIN2-) were analysed in detail. Women with hrHPV-/≥LSIL comprised 0.3% of the total. The prevalence of CIN2, CIN3, SCC or cervical adenocarcinomas in the lesions with HPV-/≥LSIL was 0.03% in the cancer screening group. Only one case of 14 cervical adenocarcinomas in ≥LSIL was hrHPV-. The prevalence of cancer missed by the shift in patients >50 years of age was significantly higher compared with patients younger than 49 years. In conclusion, the prevalence of CIN2+, which might be missed by the shift from primary cytology to primary HPV testing, was remarkably low in this Japanese cancer screening. The data indicated that primary HPV testing, which was more sensitive for CIN2+ than primary cytology, was a feasible method that can be used in Japan. In particular, primary HPV testing should be introduced for women <50 years old.

Objective: Primary high risk human papilloma virus (hrHPV) testing is recommended as first-line screening for cervical cancer. Testing involves either a clinician-collected or a self-collected cervicovaginal swab. This study examines concordance between methods of collection of primary HPV testing. Methods: Ovid MEDLINE, Ovid Embase, and Cochrane were searched for relevant studies on self-collected and clinician-collected primary HPV testing published before December 31, 2022. English-language studies for primary HPV testing of average-risk patients were included. Studies conducted in screening settings rather than colposcopy clinics, that used standard devices for HPV collection, and that directly compared methods of collection were included. Outcomes were concordance and kappa between paired samples, and rate of HPV detection in self-collected and clinician-collected samples. Results: A total of 2381 studies were screened, of which 228 were included for full-text evaluation. Thirty-six studies, including 23,328 individuals screened, met the inclusion criteria. The rate of HPV detection ranged from 4.7% to 63% for self-collection and from 3.7% to 62% for clinician-collection. The concordance ranged from 78.2% to 96.9%, and kappa had substantial agreement for 26 of the 36 studies and moderate agreement for 7 of the 36 studies. Conclusions: This study directly compares clinician-collected and self-collected primary HPV screening rates. Studies were conducted in methods which are widely reproducible in the primary care setting. Primary HPV self-collection is a reliable and accurate method for cervical cancer screening.

The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for the use of extended genotyping results in cervical cancer prevention programs. Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated using data obtained with the Onclarity HPV Assay from large cohorts. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Risk estimates were reviewed in relation to clinical action thresholds and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. Colposcopy is recommended after positive tests for human papillomavirus (HPV) types 16 and 18. For those positive for HPV 45, 33/58, 31, 52, 35/39/68, or 51 but negative for 16 or 18, triage with cytology or dual stain testing is recommended. When screening with primary HPV testing, for patients who test positive for HPV types 56/59/66 and no other carcinogenic types, repeat HPV testing in 1 year is recommended. When screening with cotesting, for those who test positive for HPV types 56/59/66 and no other carcinogenic types, 1-year return is recommended for negative for intraepithelial lesion or malignancy, atypical squamous cells of undetermined significance, and low-grade squamous intraepithelial lesion, and colposcopy is recommended for atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H), atypical glandular cells, high-grade squamous intraepithelial lesion, or carcinoma. When patients without prior high-grade cytology (atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, atypical glandular cells, high-grade squamous intraepithelial lesion, or carcinoma) or histology (cervical intraepithelial neoplasia [CIN]2, CIN3, or adenocarcinoma in situ) are being followed, use of extended genotyping results is acceptable. When high-grade cytology or histology results are present, or when patients are being followed after treatment of CIN2+, management using the 2019 guidelines is recommended. Human papillomavirus extended genotyping can guide clinical management in the setting of a positive HPV test result.

Primary HPV testing recommendations of US providers, 2015

As most women diagnosed with cervical carcinoma have been “inadequately screened,” improvements in screening are critical. After abnormal Pap test findings (through liquid-based cytology), residual specimens now can be tested simultaneously for oncogenic types of Human Papilloma virus (HPV). If these “reflex” HPV tests are negative, Pap tests need not be repeated for 12 months. Women with positive oncogenic HPV tests, however, can be referred immediately for colposcopy. There has been concern that “stigma” issues could be associated with positive HPV status (because of its sexual transmission) that might cause women to avoid this reflex HPV testing. We addressed this concern by assessing whether stigma issues surface in relation to HPV testing. We randomly selected 20 women and administered to them semistructured telephone interviews that included responses to a scenario of reflex HPV–DNA testing. Interview transcripts were analyzed qualitatively. Highly limited knowledge levels were found about HPV, but, following education about screening options, there was no rejection of HPV testing. In conclusion, it appears that women favor reflex HPV testing due to its “convenience” and perceptions that it is “the least intrusive option more definitive than Pap testing.”

BackgroundHigh-risk Human Papillomavirus (HPV) testing is replacing cytology in cervical cancer screening as it is more sensitive for preinvasive cervical lesions. However, the bottleneck of HPV testing is the many false positive test results (positive tests without cervical lesions). Here, we evaluated to what extent these can be explained by cross-reactivity, i.e. positive test results without evidence of high-risk HPV genotypes. The patterns of cross-reactivity have been thoroughly studied for hybrid capture II (HC2) but not yet for newer HPV assays although the manufacturers claimed no or limited frequency of cross-reactivity. In this independent study we evaluated the frequency of cross-reactivity for HC2, cobas, and APTIMA assays.MethodsConsecutive routine cervical screening samples from 5022 Danish women, including 2859 from women attending primary screening, were tested with the three evaluated DNA and mRNA HPV assays. Genotyping was undertaken using CLART HPV2 assay, individually detecting 35 genotypes. The presence or absence of cervical lesions was determined with histological examinations; women with abnormal cytology were managed as per routine recommendations; those with normal cytology and positive high-risk HPV test results were invited for repeated testing in 18 months.ResultsCross-reactivity to low-risk genotypes was detected in 109 (2.2 %) out of 5022 samples on HC2, 62 (1.2 %) on cobas, and 35 (0.7 %) on APTIMA with only 10 of the samples cross-reacting on all 3 assays. None of the 35 genotypes was detected in 49 (1.0 %), 162 (3.2 %), and 56 (1.1 %) samples, respectively. In primary screening at age 30 to 65 years (n = 2859), samples of 72 (25 %) out of 289 with high-risk infections on HC2 and < CIN2 histology were due to cross-reactivity. On cobas, this was 106 (26 %) out of 415, and on APTIMA 48 (21 %) out of 224.ConclusionsDespite manufacturer claims, all three assays showed cross-reactivity. In primary cervical screening at age ≥30 years, cross-reactivity accounted for about one quarter of false positive test results regardless of the assay. Cross-reactivity should be addressed in EU tenders, as this primarily technical shortcoming imposes additional costs on the screening programmes.

Michaela had a Papanicolaou (Pap) test at age 17, less than 3 months from her first intercourse. The test was interpreted as atypical squamous cells of undetermined significance (ASC-US) and the laboratory automatically “reflexed” this to human papillomavirus (HPV) testing. Michaela tested positive for high-risk (carcinogenic) HPV, had colposcopy and biopsy and cryotherapy for cervical intraepithelial neoplasia, grade 1 (CIN 1). The result from her 4-month postcryo Pap test was ASC-US HPV positive.So what is the problem with Michaela's story? Everything! According to national guidelines, (1) she should not have had her first Pap test until 3 years after her first intercourse or age 211–4; (2) she should not have had HPV testing after the ASC-US interpretation of her Pap test unless she was at least 21 years old34; and (3) as an adolescent, she should not have had colposcopy for a minor Pap test abnormality or cryotherapy to treat cervical intraepithelial neoplasia 1 (CIN 1).34Why is it so important to adhere to national guidelines? Don't we (clinicians) know what is best for our patients? Well, clinically we know our patient best, and guidelines cannot foresee every variation in real clinical practice. However, guidelines created through rigorous evaluation of evidence-based data and a consensus process provide a framework for providing care that is optimum for most women at each phase in the timeline of their life. Guidelines cannot, and should not, trump clinical decisions for a unique patient situation.34 But variations from recommended guidelines should be the exception rather than the rule in clinical practice.Perhaps we need to go back to the beginning, to the dialogue between the King and the white rabbit in Lewis Carroll's wonderful Alice in Wonderland: “Where shall I begin, please, your majesties?” Like the King we will say, “Begin at the beginning and go until you come to the end. Then stop!” So, to understand how we can best protect our patients from cervical cancer, let's begin at the beginning …Cervical cancer is the first cancer identified as having a single obligatory cause, cervical infection by human papillomavirus (HPV).5 However, HPV is common; cervical cancer is not. Almost all who are sexually active have had 1 or more HPV infections in their life.5 Some HPV types are associated with cervical precancer and cancer and are therefore called “high risk” (also carcinogenic or oncogenic) HPV types. Other types that do not cause cancer are called “low-risk” HPV types. Most HPV infections, including those caused by high-risk HPV types, are benign, transient, and resolve spontaneously within a year or 2. Less commonly, high-risk HPV infections persist. The longer high-risk HPV infections persist, the more likely they are to cause a precancerous lesion, which, if not detected and treated in a timely fashion, can become cancerous.5 Fortunately, cancer is an uncommon outcome for an infection virtually everyone gets. The entire process of cervical carcinogenesis, from causal infection to invasive cancer, is usually slow, taking many years or decades. The success of cervical cytology, despite its limitations in sensitivity,67 has been the result of repeated screening, detection, and therapeutic intervention during the long sojourn from causal infection to invasion.8Testing for the virus that causes cervical cancer certainly makes sense because cervical cancer rarely, if ever, occurs without HPV. However, the natural history of HPV-induced carcinogenesis and the ubiquitous nature of HPV must temper and guide how we use HPV testing. Most young women are infected with HPV within a few years of becoming sexually active, but exceedingly few have precancer and far fewer still have cancer. Meanwhile older women have fewer HPV infections and are at greater risk for having precancer and cancer if they test positive for HPV. Misuse of HPV testing in young women identifies too many women with HPV who are not at risk for cervical cancer.For Michaela the harm was a Pap test when she had no risk of cervical cancer, while the likelihood of obtaining an abnormal cervical cytology result was very, very high; a HPV test at an age when HPV is ubiquitous and carries little prognostic value; the anxiety and discomfort of triage to colposcopy and cervical biopsy for HPV lesions of little risk; and the mental and physical trauma of cervical treatment for often transient CIN 1, a diagnosis that is synonymous with HPV infection. Although cryotherapy has not been shown to cause adverse reproductive outcomes, too many young women with minor abnormalities are being treated by cervical excision procedures (eg, loop electrosurgical excision or laser cone) that may increase the risk 2 to 4 fold of premature delivery and low-birth-weight infants.9–11Such a risk is acceptable if necessary to prevent progression to cervical cancer. But since there is so little cancer risk at Michaela's young age, our primary consideration is to avoid harm when there is little benefit. (The US rates of cervical cancer in women under the age of 25 are 2 in 100 000, only slightly higher than the rates of vaginal cancer, for which there is no screening recommended.) This is such an important tenet that if HPV testing is inadvertently performed in an adolescent, the results should be ignored and not be used to influence patient management.4As summarized by the HPV DNA Test Utilization Statement,12—based on the consensus guidelines developed by the American Society for Colposcopy and Cervical Pathology4 and endorsed by the American Cancer Society, American Society for Clinical Pathology, American Society for Colposcopy and Cervical Pathology, American Society of Cytopathology, American Society for Cytotechnology, College of American Pathologists, International Academy of Cytology, and Papanicolaou Society of Cytopathology— there is clear, documented benefit for HPV testing in the circumstances listed in the document.Human papillomavirus testing must be for high-risk HPV (HR-HPV) types only and should use an FDA-approved or equivalent test that has undergone peer review of a rigorous, masked evaluation involving an adequate sample size.13 Testing for low-risk HPV types that do not cause cervical cancer has no clinical benefit and therefore cannot be justified or condoned.13 Other than the indications listed in the HPV DNA Test Utilization Statement, HR-HPV testing generally should not be done because it potentially creates more harm than benefit. Importantly, cotesting with the Pap and HPV tests in women age 30 and older should not be done more frequently than every 3 years if both tests are negative. This combination of tests provides safety for at least 3 years, with recent studies1415 suggesting safety may extend for at least 6 years. Hence, testing more often of women who are at virtually no risk of having precancer adds cost without benefit. Excessive screening all too often identifies transient HPV infections and minor cytologic abnormalities that would resolve on their own if given wider screening intervals,16 adding unnecessary evaluations and procedures that create patient harm.Human papillomavirus testing should be avoided as a reflex test to any abnormal Pap test other than in cases of ASC-US, except in postmenopausal women with low-grade squamous intraepithelial lesion (LSIL). Less than 50% of postmenopausal women have LSIL due to HPV, and those with HPV-negative LSIL are at low risk for cancer and do not need colposcopy.Neither should HPV testing be done during the initial management of women with atypical glandular cells (AGC). Women with AGC may not have HPV-induced lesions—ie, tubal metaplasia of the endocervix, reactive endocervical cell changes, atypical endometrial hyperplasia, endometrial carcinoma, glandular lesions in the fallopian tubes, and ovary and glandular cancers from a variety of sources metastatic to the pelvis. However, once possible sources of a non-HPV induced lesion have been eliminated and colposcopy has not detected CIN or adenocarcinoma in situ (AIS), HPV testing can provide important information regarding the best follow-up option for women with AGC “not otherwise specified” (AGC NOS). Women with AGC NOS who are positive for high-risk HPV are at greater risk for subsequent detection of CIN 2/3 or AIS and are best followed up with a repeated Pap test and HPV test in 6 months, with referral back to colposcopy if either is abnormal. This is 1 of only 2 exceptions to the general rule that a positive HPV test result should not be repeated in less than a year. The other exception is in the 6-month surveillance period of women treated for CIN 2/3.There are a number of other areas for which HPV testing should not be done but are not mentioned in the HPV DNA Test Utilization Statement. Human papillomavirus testing should never be used as a screening test for sexually transmitted diseases (STDs) because HPV is so common and, unlike most STDs, has no treatment that would follow detection. Human papillomavirus testing should not be done as a screen prior to administering the HPV vaccine. The FDA-approved HPV test identifies a pool of high-risk HPV types and is not restricted to the 4 HPV types in the vaccine (HPV 6, 11, 16, and 18). Additionally, there is no commercially available serologic test that would identify past exposure to these 4 HPV types. The cost of prevaccination screening of all sexually active women would escalate the cost of vaccine administration. Human papillomavirus vaccination programs should target populations that will glean the greatest benefit for the cost: girls in early adolescence who are mostly naïve to HPV infections.17The HPV DNA Test Utilization Statement represents a convergence of many professional societies for the best practice of HPV testing in the screening and management of women for prevention of cervical cancer. The underpinnings for these recommendations, based on the ASCCP guidelines,4 are the natural history and epidemiology of HPV and cervical cancer. The underlying principle for using any screening or diagnostic test is to differentiate effectively those at risk of disease from those who are not.1819However, there must be an acknowledgment that no test, diagnostic procedure, or treatment is error-free. No measures can be taken to provide absolute reassurance against cervical cancer. As tests for high-risk HPV have become available, there is the misconception that its exhaustive use might eliminate all cervical cancer. Yet, excessive screening may result in excessive management and harmful treatment for benign conditions, while minimally reducing cancer incidence; most cases of cervical cancer (60%) occur in pockets of underscreened populations (http://www.cdc.gov/cancer/cervical/). For women of Michaela's age group, it is unproven whether additional or more sensitive screening can eliminate any of the rare cancers in women younger than 25 years.For those clinicians, laboratories, and pathologists conducting (or promoting) more HPV testing for financial gain,20 it is important to understand the risks being taken. The Pap test has been the most successful cancer screening test in the history of modern medicine. As a result, we have seen a drop in incidence of cervical cancer and its precursors. Consequently, a “positive” Pap test result is more likely to be a false-positive than a true-positive. The reason that HPV testing is such a powerful adjunct to cervical cytology is that it clarifies risk: women (aged 21 or older) with HPV-negative ASC-US are at exceedingly low risk of precancerous lesions21 and can return to routine screening without further clinical intervention, while women with HPV-positive ASC-US have a risk comparable to that associated with an LSIL cytologic profile. Prior to the advent of HPV testing, the patients with equivocal Pap results would most often have repeated Pap tests, multiple colposcopic evaluations with possibly multiple biopsies, all of which could lead to patient morbidity. With HPV testing, we can weigh the risk of having significant cervical disease against the costs of unnecessary intervention and harm.For HPV testing to fulfill its promise, clinicians must understand under which circumstances it should be used and under which it should not. Laboratories must question their client clinicians when HPV testing is ordered in a situation that is more likely to cause harm than benefit. Clinicians must not threaten to move their business to another laboratory as has been done when the laboratory refuses to do HPV testing that is not clinically indicated by the guidelines. Clinicians must also question the motives of laboratorians that urge HPV testing that is not in accordance with guidelines. We all share in the responsibility of making our patients as safe from harm as reasonably possible and making medicine as protective and cost-effective as possible. “Where shall I begin, please, your majesties?” Begin with understanding how common HPV is, yet how it can cause cervical cancer. Use your understanding of the natural history of HPV to make sage decisions that lead you to the best choices for your patients, choices that emphasize benefit and minimize harm. When we all reach that goal, we can feel confident that we have fulfilled that promise that we made when we took the Hippocratic oath, “First do no harm.”