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Chapter 7: Cervicitis

Women with vaginal discharge, with or without evidence of vaginitis, should be carefully evaluated for cervicitis. Clinically, two types of cervicitis can be distinguished, based on the location of cervical inflammation and exudate: endocervicitis (also known as mucopurulent cervicitis or MPC) and ectocervicitis.

ETIOLOGY/EPIDEMIOLOGY

The two main sexually transmitted agents classically responsible for clinically apparent endocervicitis are Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhea). Herpes simplex virus (HSV) can cause either endocervicitis or ectocervicitis. Trichomonas vaginalis (T. vaginalis), bacterial vaginosis (BV), and C. albicans can produce ectocervicitis. 

Chlamydia is the most common bacterial STD in the United States. Untreated, chlamydial infections can lead to pelvic inflammatory disease (PID), tubal infertility and chronic pelvic pain. Because the majority of infections in women are asymptomatic and do not usually cause visible signs of cervicitis, CDC recommends C. trachomatis screening at least annually for all women aged 25 years of age and younger. 

Genital infections secondary to N. gonorrhoeae may produce no recognizable symptoms in women until complications (e.g., PID) have occurred. Although widespread screening among women is not recommended, targeted screening of young women (<25) is favored for control and prevention of a number of reproductive health sequelae secondary to untreated gonorrhea.  Per the U.S. Preventive Services Task Force, populations at risk for gonorrhea include: women with previous gonorrhea, other STDs, new or multiple sex partners, and inconsistent condom use; those who engage in commercial sex work and drug use; women in certain demographic groups; and those living in communities with a high prevalence of disease.

In order to recognize the signs of cervical inflammation, it is important to understand the histologic changes that normally occur in the cervix during the reproductive period and menstrual cycle.  The normal cervix consists of three kinds of epithelia:

  • squamous
  • columnar
  • metaplastic squamous

Squamous epithelium covers most of the cervix and is contiguous with the vaginal epithelium. It is flat, pink, and opaque, rather like the lining of the mouth.  Columnar epithelium may be confined to the endocervical canal or may occur surrounding the cervical os, where it is often referred to as "ectopy."  Ectopy is commonly seen in young women (typically seen in women <25 years old) and in women using oral contraceptives. Columnar epithelium is redder and more like the lining of [image 2] the eyelid in appearance. These two types of epithelia meet at the squamocolumnar junction of the cervix.  These images show examples of these different types of normal cervical epithelia. [Image 1 and Image 2]

Metaplastic epithelium occurs at the squamocolumnar junction, a transformation zone where columnar epithelium is being replaced by new squamous epithelium.  As women mature, this transformation of the epithelium at the squamocolumnar junction retreats into the endocervical canal.  Since this junctional area should be sampled for a Pap smear, it is important to get an endocervical specimen, particularly in older women.  Nabothian cysts also occur in the transformation zone, which are benign, pearly white or yellow, nonfriable cysts containing clear cervical mucous [Image 3].

Image 7-1. Normal cervix without ectopy
Image 1.
Normal cervix without ectopy
Image 7-2. Normal cervix with ectopy
Image 2.
Normal cervix with ectopy
Image 7-3: Nabothian Cyst
Image 3
Nabothian cyst

CLINICAL MANIFESTATIONS

Factors which suggest the presence of cervicitis are:

  1. Endocervical discharge that is
    1. Mucopurulent [Images 4, 5, 6]
    2. Increased in amount
    3. Evidences an increased number of PMNs (>30PMNs/1000X field) on endocervical Gram stain.
  2. Easily induced endocervical bleeding (defined as sustained bleeding on gentle passage of a non-abrasive swab, such as cotton or polyester)
  3. Ectocervix with
    1. Edema in the area of ectopy, if present
Image 7-4. Mucopurulent discharge
Image 4.
Mucopurulent discharge from cervix on a swab (positive swab test)
Image 7-5. Mucopurulent cervicitis due to Chlamydia
Image 5.
Mucopurulent cervicitis due to chlamydia showing ectopy, edema, and discharge
Image 7-6. Mucopurulent cervicitis
Image 6.
Mucopurulent cervicitis

DIAGNOSIS

Neisseria gonorrhoeae

Gonococcal infections in cases of cervicitis can be diagnosed by a number of highly specific assays:

  • Nucleic acid amplification tests (NAAT) (sensitivity ≥95%). Due to its high sensitivity and specificity, NAAT is the preferred method for diagnosing gonorrhea, ideally on a self-obtained or clinician-obtained swab of vaginal fluid. Culture can be useful, however, if treatment failure due to antibiotic resistance (an increasing concern) is suspected or if administration of an alternative regimen for gonorrhea is planned.
  • Culture (sensitivity 80 to 90%)
  • Gram stain (sensitivity 50 to 60%)

Chlamydia trachomatis

As mentioned, chlamydia is a major etiologic agent of cervicitis. Most women with chlamydial infection of the cervix (80-90%) have no signs of cervicitis. NAAT, ideally performed on a self-obtained or clinician-obtained swab of vaginal fluid, is the preferred method of diagnosing chlamydial infection, and empiric treatment should be undertaken in most cases of cervicitis while testing is pending.

Image 7-7. Erosive cervicitis
Image 7.
Erosive ecto and endo cervicitis due to HSV infection

Herpes Simplex Virus

Although HSV can cause endocervicitis, more classically, primary ectocervical herpes infections often produce ulcerative, necrotic lesions that are painless. External genital lesions are also usually seen upon examination and can provide presumptive evidence of herpetic cervicitis. Cell culture and PCR are preferred for the diagnosis of HSV among patients who have visible lesions. [Image 7]

Other Agents

 As noted above, other agents may also cause cervical infection.  T. vaginalis may cause a purulent discharge and a blotchy "strawberry" ectocervix; see Chapter 6 for a discussion of diagnostic testing.  Human papillomavirus (HPV) infection may cause visible papillary warts, leukoplakia, or subclinical papillomavirus infection ("flat" condyloma, which can only be seen using a colposcope).  HPV can also be detected as koilocytosis (cells with enlarged nuclei and large perinuclear halos of cytoplasmic clearing) on a Pap smear.  NAAT are available to detect HPV DNA, but are generally restricted to use to detect HPV types that confer increased risk for cervical neoplasia ("high risk" HPV, including types 16, 18, and others).  Finally, genital ulcer disease caused by Treponema pallidum (syphilis) or Haemophilus ducreyi (chancroid) can also cause discrete lesions on the cervix.

TREATMENT

For a more detailed discussion of these regimens and other treatment considerations, please refer to the CDC STD Treatment Guidelines at http://www.cdc.gov/std/treatment/.

It is reasonable to take one of two approaches in the treatment of cervicitis. A practitioner may choose to defer treatment, while following a patient closely, until results are available. Alternatively, a practitioner may choose to empirically treat if suspicion is high for either gonorrhea (local prevalence >5%) or chlamydia (e.g., age ≤25, new or multiple sex partners, and engaged in unprotected sex). In general, for cases of frank cervicitis, the latter approach is recommended, particularly with regard to treatment for chlamydial infection given its relatively high prevalence and potential for causing adverse sequelae.

Effective treatment of gonorrhea is complicated by its ability to develop antimicrobial resistance.  Based on data from the Gonococcal Isolate Surveillance Project (GISP), the CDC recently updated its treatment recommendations from the 2010 CDC STD Treatment Guidelines. As of August 2012 (MMWR 2012), CDC no longer recommends cefixime at any dose as a first-line regiment for treatment of gonococcal infections.  Instead, ceftriaxone as a single intramuscular injection of 250 mg in combination with a second antimicrobial (azithromycin as a single 1 g oral dose or doxycycline 100 mg orally twice daily for 7 days) is recommended.  Moreover, CDC advises a test of cure at one week for any person who undergoes treatment with a non-ceftriaxone regimen.

When ceftriaxone cannot be used for treatment, two alternative options are available: cefixime 400 mg orally plus either azithromycin 1 g orally or doxycycline 100 mg twice daily orally for 7 days (with preference given to azithromycin over doxycycline) or azithromycin 2 g orally in a single dose if ceftriaxone cannot be given because of severe allergy.

Empiric treatment for gonorrhea and chlamydia while awaiting NAAT results:

Ceftriaxone 250 mg IM x1

PLUS EITHER

Azithromycin 1 g PO x1

OR

Doxycycline 100 mg PO BID x 7 days

Chlamydia trachomatis

Recommended regimen

Azithromycin 1.0 g PO single dose

OR

Doxycycline 100 mg PO bid for 7 days

Alternative regimens

Erythromycin base 500 mg orally 4 times daily for 7 days

Erythromycin ethylsuccinate 800 mg orally 4 times daily for 7 days

Levofloxacin 500 mg orally QD for 7 days

Ofloxacin 300 mg orally BID for 7 days

Neisseria gonorrhoeae

Recommended regimen

Ceftriaxone 250 mg IM in a single dose

OR, IF NOT AN OPTION

Cefixime 400mg PO (single dose)

OR

Single-dose injectable cephalosporin regimens

PLUS

Azithromycin 1 g orally in a single dose

OR

Doxycycline 100 mg orally twice daily for 7 days

 Figure 7-1 for evaluation and management of possible mucopurulent cervicitis.

Herpes Simplex Virus

See Chapter 9 for treatment information.

Trichomonas vaginalis

See Chapter 6 for treatment information.

FOLLOW-UP

Chlamydia trachomatis

When taken as directed, the doxycycline and azithromycin regimens listed are highly effective in treating chlamydia.  Therefore, post-treatment test-of-cure (repeat testing 3-4 weeks after completion of therapy) is not routinely per­formed when these recommended regimens are used.

Instead, practitioners are encouraged to pursue test-of-cure in the following scenarios:

  • pregnant patients
  • settings when adherence to therapy is in question
  • persistent symptoms despite therapy
  • reinfection is suspected

Utilization of NAAT may yield false-positive results due to the ongoing presence of nonviable organisms if used in the period of less than 3 weeks from completion of therapy, challenging its validity in this context. For this reason, test of cure (if indicated) should not be performed using NAAT until 3 weeks post-completion of therapy. All women with cervicitis due to chlamydia should undergo re-testing for this infection three months after treatment (distinct from test-of-cure), regardless of whether sex partners received treatment or not; this strategy is highly effective in detecting women who have been newly infected since their initial diagnosis.

Neisseria gonorrhoeae

Women diagnosed and treated with a first-line regimen, particularly a single injection of 250 mg intramuscular ceftriaxone (plus either azithromycin or doxycycline) for uncomplicated gonococcal cervicitis, do not require a test-of-cure except in certain scenarios. Most practitioners agree that performing a test-of-cure in pregnant women is appropriate. Certainly, women treated for gonorrhea who persistent symptoms or signs consistent with this infection should be retested. Given evolving trends in antimicrobial resistance, if treatment failure is suspected, practitioners should send cultures for antimicrobial susceptibilities if available and ideally involve a specialist for guidance in clinical management. If cultures are not available, NAAT is reasonable though limitations regarding persistent positivity in the immediate period post-treatment should be noted. Suspected cases of treatment failure should prompt involvement of state and local public health authorities.

All women with cervicitis due to gonorrhea should undergo re-testing for this infection three months after treatment (distinct from test-of-cure), regardless of whether sex partners received treatment or not; this strategy is highly effective in detecting women who have been newly infected since their initial diagnosis.

Herpes Simplex Virus

Patients should be informed about  

  • Natural history of HSV infection, including asymptomatic viral shedding
  • Rationale for and utility of suppressive antiviral therapy
  • Recommendation to abstain from sexual contact while lesions are present, even if using suppressive therapy

Human Papillomavirus

Women with visible cervical warts should undergo Pap smear and referral to a gynecologist for evaluation.

MANAGEMENT OF SEXUAL CONTACTS

Chlamydia trachomatis

All sexual contacts within the past 60 days of persons with C. trachomatis infection should treated with azithromycin 1.0 gram orally (single dose) or doxycycline 100 mg orally twice daily for 7 days.

Neisseria gonorrhoeae

Sexual partners exposed to gonorrhea within the past 60 days should be treated with a recommended cephalosporin and either azithromycin 1.0 gram orally (single dose) or doxycycline 100 mg orally twice daily for 7 days.

Herpes Simplex Virus

Routine antiviral treatment of sex partners is not indicated.

Human Papillomavirus

Routine examination and treatment is not recommended.

Trichomonas vaginalis

See Vaginitis, Chapter 6.

COMPLICATIONS/SEQUELAE

The major complications of cervical infection with the agents discussed above include:

  1. Ascending infection, which may cause endometritis or PID (resulting in chronic pelvic pain, tubal infertility or ectopic pregnancy)
  2. Neonatal infection and adverse outcomes of pregnancy
  3. Transmission of the responsible agent to sex partners
  4. Cervical neoplasia
  5. Disseminated gonococcal infection (although DGI is most commonly observed with gonococcal strains that evade complement-killing and as a result, do not cause lower genital tract signs or symptoms before dissemination) [image 8]
  6. Increased risk of acquisition of HIV and, in HIV-infected women, increased levels of HIV shed at the genital mucosa (and presumably, increased risk of transmitting HIV)
Image 8. Disseminated gonococcal infection
Image 8.
Disseminated gonococcal infection

References:
CDC. Update to CDC's sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR 2012:61(31); 590-594

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