Cervical Dysplasia

July 2006

Chapter Contents

Background

Subjective

Objective

Assessment

Plan

Patient Education

References

Background

Cervical dysplasia and cancer are associated with human papillomavirus (HPV), a sexually transmitted virus. Carcinogenic strains of HPV may, in conjunction with other factors, cause dysplasia and cancer not only of the cervix, but also of the vulva, vagina, and anus. HIV-infected women have a higher prevalence of HPV infection than HIV-uninfected women, and are 5 times more likely to develop cervical dysplasia, or squamous intraepithelial lesion (SIL), precursors to cervical cancer. They may also have a higher risk of invasive cervical cancer and tend to have more aggressive forms of cervical cancer. Invasive cervical cancer is an AIDS-defining illness.

The risk of high-grade cervical lesions appears to be higher in women with advanced immunodeficiency than in women with preserved CD4 cell counts. Other risk factors for dysplasia and cervical cancer include African American ethnicity, a history of smoking, younger age at onset of sexual intercourse, and multiple sexual partners. Effective antiretroviral therapy (ART) with immune reconstitution has not been shown to prevent the progression of dysplasia.

Screening for cervical dysplasia and appropriate intervention in women with high-grade dysplasia are effective in preventing cervical cancer. Frequent monitoring and careful follow-up in women with low-grade lesions are essential for preventing progression to invasive disease. Papanicolaou testing should be performed routinely on all HIV-infected women, with testing initiated at diagnosis, repeated 6 months after the first test, then performed annually thereafter if the results are normal. (See chapter Initial and Interim Laboratory and Other Tests .) Because the risk of anal dysplasia is also increased in HIV-infected women, many experts recommend concurrent screening for anal dysplasia. For further information, see chapter Anal Dysplasia .

Prevention of HPV infection is difficult. Latex or plastic barriers may be partially effective, although infection may occur through bodily contact outside the area covered by the barriers. A vaccine against certain strains of HPV has been approved by the U.S. Food and Drug Administration and others are expected to follow, although their efficacy in HIV-infected women and men is not yet known.

S: Subjective

Patients with cervical dysplasia or early cervical cancer are usually asymptomatic and disease will not be diagnosed unless screening is performed. Genital condylomata (warts) indicate infection with HPV and are typically associated with low-risk types of HPV; however, women with genital warts may have concurrent dysplasia. The classic symptom of early invasive cervical neoplasia is intermittent, painless bleeding between menstrual periods, which may present initially as postcoital spotting. Late symptoms of invasive cervical carcinoma include flank and leg pain, dysuria, hematuria, rectal bleeding, and obstipation.

Ask all female patients about risk factors for, and previous history of, cervical dysplasia and cancer, including the following:

• Genital warts; previous or current HPV infection
• Previous abnormal cervical Papanicolaou smear
• Previous abnormal anal Papanicolaou smear
• Previous cervical cancer; when and how treated
• Sexual activity before age 20
• History of multiple sexual partners
• Cigarette smoking
• CD4 count <200 cells/µL
• Pregnancy
• Oral contraceptive use

O: Objective

Perform a focused examination of the abdomen and pelvis. Examine the external genital and perianal region. Perform speculum and bimanual examinations to evaluate the vagina and cervix. Look for lesions, masses, warts, and cervical inflammation or discharge, as well as exophytic or ulcerative cervical lesions with or without bleeding. Note that simple visual examination may not reveal abnormalities.

A: Assessment

HIV-infected women have an increased risk of cervical dysplasia with progression to cervical cancer. If abnormalities of cervical disease are suspected, an appropriate evaluation should be performed. Because most women with cervical dysplasia have no symptoms, routine screening should be performed in all women.

P: Plan

Screening

Perform screening Papanicolaou smear on all HIV-infected women. The initial smear should be taken at the time of HIV diagnosis, a second should be taken 6 months later, and the procedure should be repeated annually thereafter if all tests are normal. If a smear is abnormal, see below. Also consider screening for anal dysplasia, with an anal Papanicolaou smear (see chapter Anal Dysplasia ).

Cervical (and anal) cytology is graded using the Bethesda 2001 system (see " References " below), which categorizes disease in increasing order of severity as follows:

• Negative for intraepithelial lesion or malignancy
• Atypical squamous cells of undetermined significance (ASCUS)
• Atypical squamous cells--cannot exclude HSIL (ASC-H)
• Low-grade squamous intraepithelial lesion (LSIL)
• High-grade squamous intraepithelial lesion (HSIL)
• Squamous cell carcinoma (SCC)

Other abnormalities may be noted, including:

• Atypical glandular cells of undetermined significance (AGUS)
• Infectious organisms such as Trichomonas

Evaluation of Cytologic Abnormalities

Atypical squamous cells of undetermined significance

If ASCUS is present without inflammation or suspected neoplastic process, several options for management exist. Most experts recommend referral for colposcopy and directed biopsy, regardless of the woman's degree of immunodeficiency. Patients who are considered reliable for follow-up may be monitored closely with repeat Papanicolaou smears every 4-6 months for 2 years until 3 consecutive tests have been negative. If a follow-up smear shows ASCUS (or higher-grade abnormalities), colposcopy with directed biopsy should be done. If the biopsy result is normal, the patient should be monitored as usual with Papanicolaou tests at 6 and 12 months. Another approach, available in some clinic settings, is to perform HPV DNA testing on a cervical sample; if HPV DNA testing shows an oncogenic HPV type, colposcopic examination should be performed.

Atypical squamous cells--cannot exclude HSIL

Women with abnormalities suggestive of high-grade dysplasia should be referred for colposcopy. HPV DNA testing can be considered to detect oncogenic HPV types.

Low-grade squamous intraepithelial lesion

Women with LSIL should be referred for colposcopy and directed biopsy.

High-grade squamous intraepithelial lesion or squamous cell carcinoma

Women with HSIL should undergo colposcopy with endocervical assessment and directed biopsy as soon as possible. Refer to an oncology specialist for treatment.

Atypical glandular cells of undetermined significance

Because of the high rate of significant lesions in patients with AGUS, colposcopy or endocervical curettage is recommended. Refer to an appropriate specialist for evaluation.

Treatment

The optimal management of precancerous cervical lesions has not been identified clearly for all classes of SIL. Consult with an HIV-experienced gynecologist, oncologist, or other dysplasia specialist.

Patient Education

• Patients who smoke should be advised to quit. Cigarette smoking appears to heighten the risk of cervical cancer, and makes HPV more difficult to treat. Discuss options for smoking cessation, and refer patients to the American Lung Association if programs are available in your area.
• Recommend the use of latex or polyurethane male or female condoms for vaginal or anal intercourse and plastic or latex barriers for oral sex to reduce the risk of transmitting HPV (the usual cause of cervical cancer) to partners. Barriers will also reduce the risk of exposure to other sexually transmitted pathogens.
• Emphasize the importance of keeping follow-up appointments for Papanicolaou smear or colposcopy to allow early detection of precancerous lesions and appropriate monitoring of abnormalities.
• For women with dysplasia who require treatment, emphasize that early treatment is essential to manage the disease and prevent the development of cancer. Advise patients to keep all medical appointments.

References

• Abularach S, Anderson J. Gynecological Problems. In: Anderson JR, ed. A Guide to the Clinical Care of Women with HIV . Rockville, MD: Health Services and Resources Administration; 2001:153. Available online at hab.hrsa.gov/publications/womencare05/. Accessed June 16, 2006.
• Centers for Disease Control and Prevention, National Institutes of Health, HIV Medicine Association/Infectious Diseases Society of America. Treating Opportunistic Infections Among HIV-Infected Adults and Adolescents . MMWR Recomm Rep. 2004 Dec 17; 53(RR15);1-112. Available online at aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=14. Accessed June 1, 2006.
• Ellerbrock TV, Chiasson MA, Bush TJ, et al. Incidence of cervical squamous intraepithelial lesions in HIV-infected women . JAMA. 2000 Feb 23;283(8):1031-7.
• Massad LS, Ahdieh L, Benning L, et al. Evolution of cervical abnormalities among women with HIV-1: evidence from surveillance cytology in the women's interagency HIV study . J Acquir Immune Defic Syndr. 2001 Aug 15;27(5):432-42.
• Newman, M. Women and HIV . In: Peiperl L, Coffey S, Volberding PA, eds. HIV InSite Knowledge Base [textbook online]. San Francisco: UCSF Center for HIV Information; March 2004. Available online at hivinsite.ucsf.edu/InSite?page=kb-03&doc=kb-03-01-12. Accessed June 1, 2006.
• Solomon D, Davey D, Kruman R, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology . JAMA. 2002 Apr 24;287(16):2114-9.
• U.S. Public Health Service, Infectious Diseases Society of America. Guidelines for preventing opportunistic infections among HIV-infected persons--2002 . MMWR Recomm Rep. 2002 Jun 14;51(RR08);1-46. Available online at aidsinfo.nih.gov/Guidelines/. Accessed June 1, 2006.
• Wright TC, Cox JT, Massad LS, et al. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities . JAMA. 2002 Apr 24;287(16):2120-9.