Cervical Cancer Screening for Women Who Attend STD Clinics or Have a History of STDs

Women attending STD clinics for the treatment of genital infection with high-risk types of Human Papillomavirus (HR-HPV) might be at increased risk for cervical cancer; persistence of HR-HPV can cause cervical cancer and its precancerous lesions. One study demonstrated an HR-HPV prevalence of 27% among women receiving treatment in an STD clinic setting; prevalence was highest among persons aged 14–19 and decreased with increasing age (418). In an evaluation of women attending STD clinics, over half of women were at increased risk for cervical cancer as a result of HPV infection, cervical disease, or history of cervical disease compared with women without these characteristics (419).

Cervical cytology (i.e., a Pap test) is an effective, low-cost screening test for preventing invasive cervical cancer. In a 2004 survey, 49% of all STD clinics in the United States reported providing cervical screening services, and 20% reported use of HPV DNA testing (419).

Current guidelines from USPSTF and ACOG recommend that cervical screening begin at age 21 years (96,97). This recommendation is based on the low incidence of cervical cancer and limited utility of screening in younger women (98). ACS recommends that women start cervical screening with Pap tests after 3 years of initiating sexual activity but by no later than age 21 years (98). Recommended screening intervals (/cancer/cervical/pdf/guidelines.pdf) should continue through 65 years according to USPSTF (http://www.uspreventiveservicestaskforce.org/uspstf/uspscerv.htm) or 70 years according to ACS (http://www.cancer.org/cancer/cervical-cancer/prevention-and-early-detection/cervical-cancer-screening-guidelines.html ).

Screening Recommendations

STD clinics that provide routine cervical screening services should follow the available guidelines. However, to ensure the provision of adequate care, follow-up and referral sources must be in place. Cervical screening should be performed using either conventional or liquid-based cytologic tests (i.e., Pap tests) and can include HR-HPV DNA tests in specific circumstances (420). For cythopathologic and HPV/DNA testing, STD clinics should use CLIA certified laboratories (421) and those that report cytopathology findings according to the following Bethesda 2001 terminology (422): atypical squamous cells (ASC), low-grade squamous intraepithelial lesions (LSIL), and high-grade intraepithelial lesions (HSIL). The ASC category is subdivided into atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells—cannot exclude HSIL (ASC-H).

During appointments in which a pelvic examination for STD screening is performed, the health-care provider should inquire about the result of the patient’s most recent Pap test and discuss the following information with the patient:

• the purpose and importance of a Pap test;
• the need for regularly scheduled Pap tests between 21–65 years of age;
• whether a Pap test will be obtained during this clinic visit; and
• if a Pap test will not be obtained during this examination, the names of local providers or referral clinics that can perform Pap tests and adequately follow up results.

If a woman has not had a Pap test during the previous 12 months (2-year intervals for women aged 21–29 years and 3-year intervals for women aged ≥30 years with a history of three normal Pap tests) and cervical screening is indicated, a Pap test should be obtained as part of the routine pelvic examination. Health-care providers should be aware that many women frequently equate having a pelvic examination with having a Pap test; they erroneously believe that a sample for Pap testing was taken, when in reality, only a pelvic examination was performed. Because self-reports of Pap tests often are not accurate, STD clinics should have a protocol for conducting cervical cancer screening and obtaining a Pap test during the routine clinical evaluation of women who do not have clinical-record documentation of a normal Pap test within the preceding 12 months and do not have another provider for screening services.

HPV Tests

HPV tests are available for clinical use and are recommended for the triage of women aged ≥21 years who have abnormal Pap test results (ASC-US). Additionally, these tests can be used in conjunction with a Pap test (adjunct testing) for cervical cancer screening of women aged ≥30 years. These tests should not be used for women aged <20 years for screening or management of abnormal Pap tests or for STD screening. Current FDA-approved HPV tests detect viral nucleic acid (DNA). Several FDA-approved tests for high-risk HPV testing are available for use in the United States. The Hybrid Capture 2 High-Risk HPV DNA test (Qiagen, Gaithersburg, Maryland) and the Cervista HPV High-Risk test (Hologics, Beford, Massachusetts) detect any of 13–14 high-risk HPV types, whereas the Cervista HPV 16/18 test detects type-specific infection with HPV types 16 and 18. The Digene HC2 HPV DNA test (Qiagen, Gaithersburg, Maryland) detects any of 13 high-risk or five low-risk HPV types, although use of this test is not indicated in the STD clinic setting (i.e., only high-risk HPV DNA testing is necessary) (423).

High-risk HPV DNA tests are recommended for the triage of women aged ≥21 years who have ASC-US cytology results. In addition, these tests are recommended for routine adjunctive testing (along with cervical cytology) used to screen women aged ≥30 years (424).

HPV DNA testing (including HR HPV and HPV 16/18 tests) is not recommended for the following situations (425-427):

• deciding whether to vaccinate for HPV;
• conducting STD screening for HPV;
• triaging LSIL;
• testing adolescents aged <21 years; and
• screening for primary cervical cancer as a stand-alone test (i.e., without a Pap test).

Women might benefit from receiving printed information about the value of and indication for cervical cancer screening (i.e., Pap testing), and they should be provided a clinic visit report that states whether a Pap test was obtained during the clinic visit. When available, a copy of the Pap test result should be provided. Women with abnormal screening or diagnostic tests should be referred to clinic settings that employ providers who are experienced in managing these cases (see Follow-Up). Cervical screening programs should screen women who have received HPV vaccination in the same manner as unvaccinated women.

Follow-Up

Among women aged ≥30 years with normal Pap tests and negative tests for HR-HPV, the screening interval can be increased to 3 years. At that time, routine testing with either a Pap test or a Pap and HR-HPV testing can resume (428).

If the results of the Pap test are abnormal, follow-up care should be provided according to the ASCCP 2006 Consensus Guidelines for Management of Abnormal Cervical Cytology (429) (information regarding management and follow-up care is available at http://www.asccp.org). If resources in STD clinics do not allow for follow-up of women with abnormal results, protocols for referral for follow-up and case management should be in place.

• According to American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines, women with Pap tests results indicating ASC-H, low- or high-grade squamous intraepithelial lesion should be referred to a clinician who can perform a colposcopic examination of the lower genital tract and, if indicated, conduct a colposcopically directed biopsy. For women aged <21 years, referral to colposcopy for ASC-US and LSIL is not recommended, because rates of spontaneous clearance are high in this population; repeat Pap testing at 12 and 24 months is recommended for these women.
• For women aged ≥21 years with a Pap test report of ASC-US, three options are available for follow-up management: 1) prompt colposcopy, 2) repeat Pap tests at 6 and 12 months, and 3) a high-risk HR HPV DNA test. Colposcopy is appropriate if the provider has concerns about adherence with recommended follow-up or concerns about other clinical indications. High-grade histological changes (i.e., CIN 2 or higher) after colposcopic evaluation for ASC-US Pap test reports is typically detected in <12% of cases. If repeat Pap tests are used (instead of prompt colposcopy) to follow ASC-US results, tests should be performed at 6- and 12-month intervals until two consecutive negative results are noted, at which time cervical cancer screening at a normal interval for age can be resumed. If subsequent Pap tests demonstrate ASC or a more serious condition, follow-up should be conducted according to ASCCP 2006 Consensus Guidelines (424). A third strategy for managing patients with ASC-US Pap test results involves testing for high-risk HPV DNA (423,424,430,431). Whereas conducting high-risk HPV testing might not be possible in some STD clinics because of resource limitations, such testing might be appropriate in other public health clinic settings. HPV tests that detect low-risk HPV types are not recommended for use in STD clinics, because they are not beneficial in this setting.
• If indicated, high-risk HPV DNA testing can be performed by 1) collecting a specimen for Pap test and HPV DNA on the same swab, 2) using a supplied swab at the time of the Pap test, if conventional cytology is used, 3) reflex testing (if liquid-based cytology is used and enough residual material is available in the cytology test vial), or 4) scheduling a separate follow-up appointment when the Pap test report results are known. If the high-risk HPV DNA test is negative, a repeat Pap test should be performed at 12 months. If the test is positive, the patient should be referred immediately for colposcopy, and if indicated, directed cervical biopsy.

Because many public health clinics (including most STD clinics) cannot provide clinical follow-up of abnormal Pap tests, women with Pap tests demonstrating low- or high-grade SIL or ASC-US usually need a referral to other local health-care providers or clinics for colposcopy and biopsy. Clinics and health-care providers who offer cervical screening services but cannot provide appropriate colposcopic follow-up of abnormal Pap tests should arrange referral to health-care facilities that will promptly evaluate and treat patients and report evaluation results to the referring clinic or health-care provider. Clinics and health-care providers should develop protocols that identify women who miss follow-up appointments so that these women can be located and scheduled for needed studies and management, and they should reevaluate these protocols routinely. Pap-test results, type and location of follow-up appointments, and results of follow-up appointment should be clearly documented in the clinic record. The establishment of colposcopy and biopsy services in local health departments, especially in circumstances in which referrals are difficult and follow-up is unlikely, should be considered if resources are available.

Other Management Considerations

The following additional considerations are associated with performing Pap tests:

• The Pap test should not be considered a screening test for STDs.
• All women receiving care in an STD-clinic setting should be considered for cervical cancer screening, regardless of sexual orientation (i.e., heterosexual women and those who identify themselves as lesbian or bisexual).
• If a woman is menstruating, a conventional cytology Pap test should be postponed, and the woman should be advised to have a Pap test at the earliest opportunity.
• If specific infections other than HPV are identified, the patient might need to have a repeat Pap test after appropriate treatment for those infections. However, in most instances (even in the presence of some severe infections), Pap tests will be reported as satisfactory for evaluation, and reliable final reports can be produced without the need to repeat the Pap test after treatment is received.
• When it is necessary to repeat the Pap test because the report was interpreted as unsatisfactory, the repeat test must be determined by the laboratory to be satisfactory and negative before screening can be resumed at regularly scheduled intervals.
• The presence of a mucopurulent discharge should not delay the Pap test. The test can be performed after careful removal of the discharge with a saline-soaked cotton swab.
• In the absence of other indications, women who have external genital warts do not need Pap tests more frequently than women who do not have warts.
• The sequence of Pap testing in relation to collection of other cervicovaginal specimens has not been shown to influence Pap test results or their interpretation (432).
• Women who have had a total hysterectomy do not require a routine Pap test unless the hysterectomy was performed because of cervical cancer or its precursor lesions. As recommended by ACOG, for women with hysterectomy resulting from CIN 2 or higher, cervical or vaginal cuff screening can be discontinued once three normal Pap tests have been documented. In these situations, women should be advised to continue follow-up with the physician(s) who provided health care at the time of the hysterectomy, if possible. In women whose cervix remains intact after a hysterectomy, regularly scheduled Pap tests should be performed as indicated (433-435).
• Health-care providers who receive basic retraining on Pap-test collection and clinics that use simple quality assurance measures are more likely to obtain satisfactory test results as determined by the laboratory. The use of cytobrushes and brooms also improves the number of satisfactory Pap tests.
• Although evidence supports the option of HPV testing for the triage of women with ASC-US Pap test results, this option might not be feasible in an STD clinic because of limited resources.
• Liquid-based cytology is an acceptable alternative to conventional Pap tests, as it has similar test-performance characteristics.

Special Considerations

Pregnancy

Pregnant women should be screened at the same frequency as nonpregnant women; however, recommendations for management differ in this population (83,84,424). A swab and an Ayre’s spatula can be used for obtaining Pap tests in pregnant women, but cytobrushes are not recommended.

HIV Infection

Several studies have documented an increased prevalence of SIL in HIV-infected women (416,436). The following recommendations for Pap test screening among HIV-infected women are consistent with most of the guidelines published by the U.S. Department of Health and Human Services (HHS) (129) and are based partially on the opinions of professionals knowledgeable about the care and management of cervical cancer and HIV infection in women.

HIV-positive women should be provided cervical cytology screening twice (every 6 months) within the first year after initial HIV diagnosis and, if both tests are normal, annual screening can be resumed thereafter. HIV-positive women with ASC-H, LSIL, or HSIL on cytologic screening should undergo colposcopic evaluation. Recommendations for management of HIV-positive women with ASC-US vary. HHS recommends a more conservative management approach (i.e., immediate colposcopy), whereas ASCCP recommends that these women be managed like HIV-negative women with ASC-US (i.e., tested for HR HPV DNA) (424,429).

Adolescents

Prevalence of HR HPV is high among adolescents aged <21 years (425). Infections in adolescent patients tend to clear rapidly, and lesions caused by these infections also have high rates of regression to normal. Therefore, ASCCP and ACOG recommend that adolescents with ASC-US or low-grade SIL be managed with repeat cytologic testing at 12 months and 24 months. Only those with HSIL at either follow-up visit or persistence of ASC-US or LSIL at 24 months should be referred for colposcopic evaluation.

Counseling Messages for Women Receiving Cervical Cancer Screening and HPV Testing

When a woman receives abnormal cervical cytology test results, she might experience considerable anxiety, distress, fear, and confusion, which can serve as barriers to follow-up care. Furthermore, a positive HPV DNA test result might exacerbate these feelings and might also elicit partner concerns, worry about disclosure, and feelings of guilt, anger, and stigmatization.

Health-care providers are the most trusted source of information about HPV and abnormal cervical cytology test results. Therefore, they have an important role to play in educating women about high-risk HPV and moderating the psychosocial impact of the diagnosis.

STD clinic providers should offer patients counseling and information both verbally and in print when delivering HPV and Pap test results. Print materials are available at several websites (https://www.cdc.gov/hpv/; http://www.ashasexualhealth.org/?s=hpv+publications). The manner in which this information is communicated to patients can influence the psychological effect of this diagnosis, as well as a woman’s likelihood of following up with necessary testing or treatment. Providers should frame high-risk HPV in a neutral, nonstigmatizing context and emphasize its common, asymptomatic, and transient nature. Also, the provider should emphasize that HPV is often shared between partners and can lie dormant for many years; having HPV does not imply infidelity, nor should it necessarily raise concerns about a partner’s health.

In counseling women with high-risk HPV infections about partner management, messages should be tailored to the individual woman’s circumstances. While no evidence supports either partner notification (PN) or clinical-evaluation referral for partners of patients with high-risk HPV, some women might benefit from having an informed discussion about their diagnosis with their partners. This type of communication can foster partner support and ensure the sharing of information that can inform decision-making (e.g., decisions regarding condom use).

The following specific key messages should be communicated to patients receiving cervical screening:

• The purpose of regular, lifelong cervical cancer screening is to identify cervical cancer precursors, which can be treated before progression to cervical cancer.
• A positive high-risk HPV DNA test or an abnormal cervical cytology test is not indicative of cervical cancer. Appropriate follow-up is necessary to ensure that cervical abnormalities do not progress.
• Some women might have a normal Pap test and a positive high-risk HPV test. A positive high risk HPV DNA test indicates a HPV infection of the cervix, but does not indicate cervical cancer. A normal cervical cytology test indicates that no cellular abnormalities were detected at the time of testing, but women who have HPV infection of the cervix have a higher likelihood of developing cell changes, which could lead to cervical cancer over time. Follow-up evaluation is essential to monitor cervical cytology.
• A Pap test that reveals ASC-US indicates some abnormal areas on the cervix that may require close follow-up or treatment so that they do not progress. Additional testing might be required to confirm these results. It is essential that patients return for all follow-up appointments and recommended tests.

Discussion concerning disclosure of a positive high-risk HPV test to sex partners might be appropriate and can include the following information:

• HPV is very common. It can infect the genital areas of both men and women. It usually has no signs or symptoms.
• Most sexually active persons get HPV at some time in their lives, though most will never know it. Even persons with only one lifetime sex partner can get HPV if their partner was infected.
• While the immune system clears HPV infection most of the time, in some persons, HPV infection does not resolve.
• No clinically validated test exists for men to determine if they have HPV infection. The most common manifestation
  of HPV infection in men is genital warts. High-risk HPV types seldom cause genital warts.
• Partners who are in a long-term relationship tend to share HPV. Sexual partners of HPV-infected patients also likely have HPV, even though they might have no signs or symptoms of infection.
• Detection of high-risk HPV infection in a woman does not mean that the woman or her partner is engaging in sexual activity outside of a relationship. HPV infection can be present for many years before it is detected, and no method can accurately confirm when HPV infection was acquired.

Prevention measures for current and subsequent sex partners and risk reduction should be discussed. Providers should counsel women about condom use depending on their current circumstances. Consistent condom use by male partners of sexually active women can reduce the risk for cervical and vulvovaginal HPV infection (25), and condom use by couples in long-term partnerships might decrease the time required to clear HPV in the infected woman. Skin not covered by a condom remains vulnerable to HPV infection. HPV vaccines are available and recommended for girls and young women aged 9–26 years, even those who have been diagnosed with HPV infection. Male partners can be vaccinated with the quadrivalent vaccine (Gardasil) to prevent genital warts.

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