What STD screening tests should I order for a patient with recent condomless sex and possible genital/oral lesions, covering HIV, syphilis, chlamydia, gonorrhea, hepatitis B and C, HSV, and HPV from urogenital, rectal, and pharyngeal sites?

Comprehensive STD Testing After Condomless Sexual Exposure

For a patient with recent condomless sex and possible genital/oral lesions, order nucleic acid amplification tests (NAATs) for chlamydia and gonorrhea from all exposed anatomic sites (urogenital, rectal, pharyngeal), reverse-algorithm syphilis serology, fourth-generation HIV antibody/antigen testing, hepatitis B and C serology, and HSV NAAT from any visible lesions—but do not screen for asymptomatic HSV or HPV by serology. 1, 2

Core Testing Panel for All Patients

Bacterial STI Screening

• Chlamydia and gonorrhea NAATs should be collected from all anatomic sites of sexual contact—urogenital (urine or swab), rectal (if receptive anal intercourse), and pharyngeal (if receptive oral sex)—because extragenital infections are frequently asymptomatic and would be missed with urogenital-only testing. 1, 2, 3
• Testing simultaneously for both chlamydia and gonorrhea using the same specimen type maximizes detection efficiency for the most common treatable STIs. 1, 2
• For women, vaginal swab NAAT provides superior sensitivity compared to cervical specimens. 2
• For men, first-void urine or urethral swab is optimal for urogenital NAATs. 2

Syphilis Testing

• Order reverse-algorithm syphilis serology: treponemal-specific test first (T. pallidum antibody via EIA/chemiluminescence immunoassay), followed automatically by nontreponemal testing (RPR) to confirm active disease. 1, 2
• This approach is now standard in most U.S. laboratories and provides higher sensitivity than traditional RPR-first screening. 1

HIV Screening

• Fourth-generation HIV testing (combined HIV antibody and p24 antigen) allows earlier detection of infection—typically 2-4 weeks post-exposure versus 3-6 weeks for antibody-only tests. 2
• HIV screening is recommended for all sexually active persons aged 13-64 seeking STI evaluation. 1

Hepatitis Screening

• Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) to detect acute or chronic infection. 1, 2
• Hepatitis C antibody with reflex to RNA PCR if positive, because sexual transmission of hepatitis C occurs particularly among men who have sex with men. 1

Trichomonas Testing

• Trichomonas vaginalis NAAT (vaginal swab for women) is optimal for detection, as wet mount microscopy misses 30-40% of infections. 2
• This is especially important for women under 25 years or those with multiple partners. 2

Lesion-Specific Testing

When genital or oral lesions are present, three tests are mandatory regardless of lesion appearance: 1

1. Syphilis serology (as described above)
2. HSV NAAT from the lesion—preferred over viral culture because NAATs provide typing (HSV-1 vs HSV-2), have higher sensitivity especially for nonulcerative or healing lesions, and remain positive longer than culture. 1
3. HIV screening—because inflammatory epithelium in genital lesions enhances HIV transmission risk. 1

Critical Pitfall: HSV Serology

• Do NOT order HSV serology (blood test) for asymptomatic patients or those without active lesions, as there is no evidence that treating asymptomatic HSV improves outcomes, and false-positive results are common in low-prevalence populations. 2
• Type-specific glycoprotein G-based HSV serology can distinguish HSV-1 from HSV-2, but should only be used in specific clinical contexts, not routine screening. 1

Tests NOT Recommended

HPV Testing

• No HPV blood test exists—HPV is detected only via cervical/anal cytology or direct visualization of lesions. 2
• HPV screening is not part of routine STD exposure workup; it is reserved for cervical cancer screening in women over 30 years. 1

Herpes Simplex Virus Serology

• HSV screening is explicitly NOT recommended for asymptomatic patients, as treatment of asymptomatic HSV does not improve clinical outcomes. 2

High-Risk Population Modifications

Men Who Have Sex with Men (MSM)

• Test all three anatomic sites (urogenital, rectal, oropharyngeal) for chlamydia and gonorrhea based on reported sexual practices, as rectal and pharyngeal infections are frequently asymptomatic. 1, 2, 3
• Consider every 3-6 month screening intervals for MSM with multiple or anonymous partners, methamphetamine use, or sex in conjunction with drug use. 2, 3, 4

HIV-Positive Patients

• Screen for all bacterial STIs (chlamydia, gonorrhea, syphilis, trichomoniasis) every 3-6 months, because co-infection increases HIV transmission risk. 2

Pregnant Women

• Universal screening at first prenatal visit for HIV, syphilis, and hepatitis B is mandatory. 1, 2
• Screen for chlamydia and gonorrhea if under 25 years or at increased risk. 1, 2

Timing Considerations

Immediate Testing (At Presentation)

• All bacterial STI NAATs (chlamydia, gonorrhea, trichomonas) can be detected within 1-2 weeks of exposure. 4
• Syphilis and HIV require 4-12 weeks for reliable antibody detection, so immediate testing establishes baseline status. 4

Follow-Up Testing

• Repeat HIV and syphilis testing at 3 months if initial tests are negative, to account for window periods. 1, 4
• Mandatory retesting at 3 months for any positive chlamydia or gonorrhea result, regardless of whether partners were treated, due to reinfection rates of 25-40%. 1, 2, 4

Partner Management and Reporting

• All sexual partners from the past 60 days must be notified and treated presumptively before test results when indicated. 2
• Expedited partner therapy should be considered where legally permissible. 2
• Syphilis, gonorrhea, chlamydia, and HIV are reportable in all U.S. states—consult local health department for specific requirements. 1, 2

Common Pitfalls to Avoid

• Do not rely on symptoms alone—70% of HSV and trichomonas infections and 53-100% of extragenital gonorrhea and chlamydia infections are asymptomatic. 5
• Do not omit extragenital testing in MSM—rectal and pharyngeal infections are often missed with urogenital-only testing. 1, 2, 3
• Do not use Gram stain for pharyngeal specimens—it has insufficient sensitivity and is not recommended. 1, 3
• Do not order HSV or HPV serology—these are not part of routine STD exposure workup. 2
• Most apparent "treatment failures" are actually reinfections from untreated sexual partners, emphasizing the critical importance of partner notification and treatment. 1