Sexually transmitted infections (STIs), often referred to as sexually transmitted diseases or STDs, include a variety of pathogenic bacteria, virus, and other microorganisms that are spread through sexual contact and can cause a multitude of complications if left untreated. Chlamydia and gonorrhea, caused by Chlamydia trachomatis and Neisseria gonorrhoeae, respectively, have high rates of occurrence in the United States and can cause pelvic inflammatory disease (PID), infertility, and pregnancy complications. The causative agent of syphilis is Treponema pallidum; if left untreated, syphilis can lead to serious cardiac and neurological conditions (Ghanem & Tuddenham, 2024). Human papillomavirus (HPV) is a double-stranded DNA virus that can be sexually transmitted and is associated with cervical cancer, vulvar/vaginal cancer, anal cancer, oropharyngeal cancer, penile cancer, and both genital and nongenital warts. “Globally, anogenital HPV is the most common sexually transmitted infection” with an estimated 80% of sexually active adults exposed to it at least once in their lifetime (Palefsky, 2024). Herpes simplex virus (HSV) is a common STI where many individuals are asymptomatic. HSV infection has been linked to an increased risk of other infections, including HIV, and in rare cases, can also result in HSV meningitis or proctitis (Albrecht, 2024). In general, risk factors for STIs can include both behavioral elements, such as multiple sex partners, working in a sex trade, and inconsistent use of condoms when in non-monogamous relationships as well as demographic risks, including men who have sex with men (MSM), prior STI diagnosis, admission to correctional facilities, and lower socioeconomic status (Ghanem & Tuddenham, 2024). 

This policy is limited to testing for C. trachomatis, N. gonorrhoeae, T. pallidum, T. vaginalis (for guidance on T. vaginalis in vaginitis, see AHS-M2057-Diagnosis of Vaginitis Including Multi-Target PCR Testing), HSV, and HPV.  The following conditions and/or tests are discussed in the corresponding policies:

•    Human Immunodeficiency Virus: CAM 282 
•    Hepatitis B and C: CAM 127-Hepatitis Testing
•    Cervical Cancer Screening: CAM 314
•    Pathogen Panel Testing: CAM 181

For STI screening in pregnant individuals, please see CAM 119-Prenatal Screening (Nongenetic).

Policy 
Application of coverage criteria is dependent upon an individual’s benefit coverage at the time of the request. 

1. Antibody testing for syphilis infection is considered MEDICALLY NECESSARY in the following situations:
   1. For any asymptomatic person in a high-risk category (see Notes 1 & 2), once a year assessment using either a “standard” or “reverse” algorithm that includes initial and confirmatory tests for any initial positive test, such as:
      1. Treponemal Ig test and
      2. Nontreponemal Ig test.
   2. For diagnosis of any person presenting with signs and/or symptoms of a syphilis infection (see Note 3).
   3. Once every three months for HIV-positive men or MSM.
   4. Treponemal Ig testing and nontreponemal testing (once prior to transplant) as a part of a pre-transplant assessment in both donors and recipients of an allogeneic hematopoietic stem cell transplantation (allo-HCT).
   5. When a nontreponemal test is used as a test of cure (TOC) for a positive syphilis infection.
2. For asymptomatic individuals NOT belonging to a high-risk category (see Notes 1 & 2), antibody screening for syphilis is considered MEDICALLY NECESSARY only in the following situations:
   1. As part of newborn screening.
   2. As part of follow-up in a victim of sexual assault.
   3. For sexually active individuals less than 18 years of age (annually).
3. Polymerase chain reaction (PCR) testing and nucleic acid amplification testing (NAAT) for syphilis is considered NOT MEDICALLY NECESSARY.
4. NAAT for chlamydia is considered MEDICALLY NECESSARY in the following situations:
   1. Once a year assessment for any asymptomatic person in a high-risk category (see Notes 1& 4).
   2. For diagnosis of any person presenting with signs and/or symptoms of a chlamydial infection (see Note 5).
   3. For the diagnosis of any person with suspected lymphogranuloma venereum (LGV).
   4. At least three months after initial chlamydial diagnosis as a TOC.
5. For asymptomatic individuals NOT belonging to a high-risk category (see Notes 1 & 4), screening for chlamydia is considered MEDICALLY NECESSARY only in the following situations:
   1. As part of newborn screening.
   2. As part of follow-up in a victim of sexual assault.
   3. For sexually active individuals less than 18 years of age (annually).
6. Serology testing for chlamydia or LGV is considered NOT MEDICALLY NECESSARY.
7. NAAT for gonorrhea is considered MEDICALLY NECESSARY in the following situations:
   1. Once a year assessment for any asymptomatic person in a high-risk category (see Notes 1 & 4).
   2. For diagnosis of any person presenting with signs and/or symptoms of a gonorrheal infection (see Note 6).
   3. As a TOC for treatment.
8. For an individual that does not respond to initial treatment, culture testing for N. gonorrhoeae to determine antimicrobial susceptibility is considered MEDICALLY NECESSARY.
9. For asymptomatic individuals NOT belonging to a high-risk category (see Notes 1 & 4), screening for gonorrhea is considered MEDICALLY NECESSARY only in the following situations:
   1. As part of newborn screening.
   2. As part of follow-up in a victim of sexual assault.
   3. For sexually active individuals less than 18 years of age (annually).
10. NAATs or PCR-based testing for T. vaginalis is considered MEDICALLY NECESSARY in the following situations:
    1. Symptomatic individuals (see Note 7).
    2. Asymptomatic individuals belonging to a high-risk group:
    3. Concurrent STI or history of STIs.
    4. Individuals in high prevalence settings, such as STI clinics.
    5. Individuals who exchange sex for payment.
11. Rapid identification of Trichomonas by enzyme immunoassay is considered NOT MEDICALLY NECESSARY.
12. For symptomatic individuals (see Note 8), testing for Mycoplasma genitalium using NAAT is considered MEDICALLY NECESSARY.
13. For asymptomatic individuals (see Note 8), screening for M. genitalium using NAAT is considered NOT MEDICALLY NECESSARY.
14. When an individual meets any of the conditions described above, multitarget PCR testing (targets limited to C. trachomatis, N. gonorrhoeae, T. vaginalis, and M. genitalium) is considered MEDICALLY NECESSARY.
15. For individuals with active genital ulcers or mucocutaneous lesions, nucleic acid amplification testing (NAAT) for herpes simplex virus-1 (HSV-1) or herpes simplex virus-2 (HSV-2) is considered MEDICALLY NECESSARY.
16. Immunoassay testing for HSV-1 and and/or herpes simplex (non-specific type test) is considered NOT MEDICALLY NECESSARY.
17. Type-specific serologic testing for HSV-2 using a glycoprotein G2 (gG2) test is considered MEDICALLY NECESSARY in the following situations:
    1. Recurrent or atypical genital symptoms or lesions in individuals with a negative herpes simplex virus PCR or culture result.
    2. For the clinical diagnosis of genital herpes in individuals with a negative PCR or culture result or without laboratory confirmation.
    3. When an individual’s partner has genital herpes.
18. In asymptomatic individuals, screening for HSV-1 or HSV-2 is considered NOT MEDICALLY NECESSARY.
19. In the diagnosis and/or assessment of cancer or cancer therapy (immunohistochemistry testing for p16 or NAAT testing for high-risk human papillomavirus [HR-HPV]), testing for HR-HPV is considered MEDICALLY NECESSARY.
20. Testing for HPV is considered NOT MEDICALLY NECESSARY in the following situations:
    1. To screen for oncogenic high-risk types, such as HPV-16 and HPV-18, as part of a general sexually transmitted disease (STD) or sexually transmitted infection (STI) screening process or panel for asymptomatic individuals.
    2. As part of the diagnosis of anogenital warts.
    3. To screen for low-risk types of HPV.
    4. In the general population, either as a part of a panel of tests or as an individual NAAT to determine HPV status.
21. Prior to beginning a preexposure prophylaxis (PrEP) regimen, the following screens/tests is considered MEDICALLY NECESSARY:
    1. Serum creatinine and estimated creatinine clearance to determine baseline renal function.
    2. Antibody screening to confirm a baseline negative antibody result for HIV.
    3. Hepatitis B (HBV) and/or Hepatitis C screening to identify positive individuals.
    4. Pregnancy testing.
22. While an individual is undergoing a preexposure prophylaxis (PrEP) regimen for HIV prevention, the following screens/testsis considered MEDICALLY NECESSARY:
    1. A blood test once every three months to confirm a negative antibody result for HIV.
    2. Serum creatinine and estimated creatinine clearance three months after beginning PrEP and up to one time every six months thereafter to assess renal function.
    3. NAAT screening, based on anatomic site of exposure, for gonorrhea and chlamydia:
       1. Once every three months for MSM and for individuals with child-bearing potential.
       2. Nine months after PrEP is initiated and once every six months thereafter for sexually active individuals.
    4. Blood test to screen for syphilis once every three months in MSM and individuals with child-bearing potential.
       1. Once every three months for MSM and for individuals with child-bearing potential.
       2. Nine months after PrEP is initiated and once every six months thereafter for sexually active individuals.
    5. Pregnancy testing once every three months.

The following does not meet coverage criteria due to a lack of available published scientific literature confirming that the test(s) is/are required and beneficial for the diagnosis and treatment of an individual’s illness.

23. Nucleic acid testing to determine antimicrobial susceptibility in N. gonorrhoeae or macrolide resistance in M. genitalium is considered NOT MEDICALLY NECESSARY.
24. Using nucleic acid testing to quantify the following microorganisms is considered NOT MEDICALLY NECESSARY:
    1. Chlamydia trachomatis
    2. Neisseria gonorrhoeae
    3. Herpes Simplex Virus-1
    4. Herpes Simplex Virus-2
    5. Human Papillomavirus
    6. Treponema pallidum

NOTES:

Note 1: For sexually active children and adolescents under the age of 18, risk factors for chlamydia, gonorrhea, and/or syphilis infection as defined by the CDC include: initiating sex early in adolescence; living in detention facilities; receiving services at STD clinics; being involved in commercial sex exploitation or exchanging sex for drugs, money, food, or housing; having multiple sex partners, having sequential sex partnerships of limited duration or concurrent partnerships; failing to use barrier protection consistently and correctly; having lower socioeconomic status, and facing numerous obstacles to accessing healthcare. At-risk individuals also include: males who have sex with males (YMSM); transgender youths; youths with disabilities, substance abuse, or mental health disorders (CDC, 2021c).

Note 2: High-Risk for Syphilis (Cantor et al., 2016; CDC, 2023a)

• Sexually active men who have sex with men (MSM)
• Sexually active HIV-positive status
• Having a sexual partner recently diagnosed with a STI
• Exchanging sex for money or drugs
• Individuals in adult correctional facilities
• During pregnancy when the following risk factors are present:
  • Sexually active HIV-positive status
  • Sexually active with multiple partners
  • Sexually active in conjunction with drug use or transactional sex
  • Late entry to prenatal care (i.e., first visit during the second trimester or later) or no prenatal care
  • Methamphetamine or heroin use
  • Incarceration of the woman or her partner
  • Unstable housing or homelessness 

Note 3: Signs and Symptoms of a Syphilis Infection (CDC, 2018, 2023a)

• Chancre
• Skin rash and/or mucous membrane lesions in mouth, vagina, anus, hands, and feet
• Condyloma lata
• Secondary symptomology can include fever, fatigue, sore throat, swollen lymph nodes, weight loss, muscle aches, headache, and hair loss
• Signs and symptoms of neurosyphilis can include severe headache, trouble with muscle movements, muscle weakness or paralysis (not being able to move certain parts of the body), numbness, and changes in mental status (trouble focusing, confusion, personality change) and/or dementia (problems with memory, thinking, and/or making decisions).
• Signs and symptoms of ocular syphilis can include eye pain or redness, floating spots in the field of vision (“floaters”), sensitivity to light, and changes in vision (blurry vision or even blindness).
• Signs and symptoms of otosyphilis may include hearing loss, ringing, buzzing, roaring, or hissing in the ears (“tinnitus”), balance difficulties, and dizziness or vertigo.
• Signs and symptoms of late/tertiary syphilis include inflammatory lesions of the cardiovascular system (e.g., aortitis, coronary vessel disease), skin (e.g., gummatous lesions), and bone (e.g., osteitis).

Note 4: High-Risk for Chlamydia and/or Gonorrhea (CDC, 2021b, 2024a, 2024d; LeFevre, 2014)

• Sexually active men who have sex with men (MSM)
• Sexually active HIV-positive status
• Sexually active women under the age of 25
• Women age 25 or over who have multiple sexual partners
• Having a sexual partner recently diagnosed with an STI
• Previous or concurrent STI
• Exchanging sex for money or drugs

Note 5: Signs and Symptoms of a Chlamydia Infection (CDC, 2021b, 2024a)

• Genital symptoms, including “discharge, burning during urination, unusual sores, or rash”
• Pelvic Inflammatory Disease (PID), including “symptoms of abdominal and/or pelvic pain, along with signs of cervical motion tenderness, and uterine or adnexal tenderness on examination”
• Urethritis
• Pyuria
• Dysuria
• Increase in frequency in urination
• Epididymitis (with or without symptomatic urethritis) in men
• Proctitis
• Sexually acquired chlamydial conjunctivitis

Note 6: Signs and Symptoms of Gonorrhea (CDC, 2024d)

• Dysuria
• Urethral infection
• Urethral or vaginal discharge
• Epididymitis (Testicular or scrotal pain)
• Rectal infection symptoms include anal itching, discharge, rectal bleeding, and painful bowel movements

Note 7: Signs and Symptoms of Trichomoniasis (CDC, 2023b)

• Vaginal or penile discharge
• Itching, burning sensation, or soreness of the genitalia
• Discomfort or burning sensation during/after urination and/or ejaculation
• Urethritis
• Epididymitis
• Prostatitis

Note 8: Signs and Symptoms of M. genitalium Infection (CDC, 2021a)

• When present, typical symptoms of Mgen-urethritis in men include dysuria, urethral pruritus, and purulent or mucopurulent urethral discharge
• When present, typical symptoms of Mgen cervicitis in women include vaginal discharge, vaginal itching, dysuria, and pelvic discomfort
• When present, typical symptoms of PID due to Mgen include mild to severe pelvic pain, abdominal pain, abnormal vaginal discharge, and/or bleeding

Terms of Terminology