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SPECIAL TOPICS IN WOMEN’S HEALTH 50 www.JAAPA.com Volume 31 Number 2 February 2018 T he CDC reports an estimated 20 million new sexually transmitted infections (STIs) in the United States each year, half in young people ages 15 to 24 years. This number is the highest ever reported. 1,2 The CDC’s director of STD prevention, Gail Bolan, MD, laments the unravelling of previously successful initiatives to reduce infection. Access to healthcare is limited in some communities and for some patients, so clinicians must make every effort to identify the often-asymptom- atic presence of STIs.

Cervicitis is a common sign of STI and delay in diagnosis can have serious sequelae and add to the already heavy burden of disease. Because of better understanding of the cause and progression of cervical cancer, new guidelines recommend routine gynecologic screening examinations at less frequent intervals than previously. 3 A consequence of this may be that asymptomatic, indolent genital infections may be missed. These infections can ascend and cause seri- ous pathology as well as increase the risk of HIV transmis- sion. 4 When patients’ sexual partners also are affected, the economic and emotional burden of this condition increases.

Noninfectious causes of cervicitis are usually chronic and include mechanical or chemical trauma, systemic in ammatory disease (such as Behçet syndrome), radiation therapy, and malignancy. 5 Clinicians need to appropriately and sensitively question patients on their risk factors for STI and any symptoms, and not be hesitant to perform diagnostic examinations and assessments if indicated.

MYCOPLASMA GENITALIUM: AN EMERGING ISSUE M. genitalium increasingly is associated with risk of cervi- citis, pelvic in ammatory disease (PID), endometritis, sus- ceptibility to HIV, and possibly infertility and adverse birth outcomes. 6,7 Clinical presentation is similar to chlamydia— often asymptomatic and with absent or only mildly elevated systemic in ammatory markers. 5M. genitalium is very difficult to culture; however, and no diagnostic test is approved by the FDA for use in the United States. 6 Nucleic acid ampli cation testing (NAAT) with polymerase chain reaction or transcription-mediated ampli cation is used in research facilities and some laboratories, and may be avail- able for high-risk populations. 6 HISTOLOGY OF THE UTERINE CERVIX The appearance of the normal cervix varies widely, with several changes during a woman’s lifespan. Under the in uence of rising estrogen levels in puberty, columnar endocervical cells evert onto the squamous ectocervical epithelium at the squamocolumnar junction. Sometimes mistaken for infection or trauma, this area of metaplasia, the transformation zone, generally is benign but may appear red and raw and be the source of postcoital and intermen- strual bleeding ( Figure 1 ). As ovarian function diminishes during menopause and after, the squamocolumnar junction recedes into the endo- cervical canal and the cervix becomes atrophic, often strikingly pale with subepithelial point hemorrhages, and susceptible to trauma. Identifying acute cervicitis in an era of less-frequent routine gynecologic examinations Margaret Allen, PA-C, MSL, DFAAPA Margaret Allen is a former PA program director for the University of Worcester in the United Kingdom, former clinical instructor in the Stanford University primary care associate program, and practiced family medicine at Ravenswood Family Health Center in East Palo Alto, Calif. The author has disclosed no potential con icts of interest, nancial or otherwise.

Roy A. Borchardt, PA-C, PhD, and Michael D. Overcash, MPAS, PA-C, department editors DOI:10.1097/01.JAA.00005 7. . Copyright © 2018 American Academy of Physician Assistants ABSTRACT Acute in ammation of the uterine cervix can lead to serious problems such as pelvic in ammatory disease (PID), endo- metritis, and complications of pregnancy and childbirth.

As intervals for routine gynecologic screening examinations lengthen, cervical infections, especially if asymptomatic, may be missed. Annual wellness examinations and other patient visits outside routine gynecologic cancer screen- ing visits should include brief evaluation with sexual risk assessment and a gynecologic examination if indicated. If cervicitis persists after standard treatment for sexually trans- mitted infections (STIs), consider Mycoplasma genitalium . Clinicians should be sensitive to the fact that the unexpected presence of infection may cause distress.

Keywords: acute cervicitis, pelvic in ammatory disease, sexually transmitted infections, Mycoplasma genitalium , gynecologic examination, mucopurulent 30271251 697 Copyright \251 2018 American Academy of Physician Assistants Identifying acute cervicitis in an era of less-frequent routine gynecolo\ gic examinations JAAPA Journal of the American Academy of Physician Assistants www.JAAPA.com 51 Nabothian cysts, epithelial cysts, and cervical broids have no pathologic signi cance. Cervical endometriosis is generally considered inoffensive despite the sometimes- alarming appearance of scattered 1- to 3-mm blue-red or blue-black lesions. Cervical polyps are friable and may wick bacteria into the endocervix; they should be curetted and sent to pathology (Figure 2). Normal cervical exudate can be scant or copious; clear or white; and thin, thick, or stringy. Reassure patients that normal discharge may vary depending on the stage of the menstrual cycle and whether the woman is ovulating, lactating, or sexually aroused. Chronic disease, increased estrogen levels from oral contraceptives, menopause, older age, or trauma all can cause alterations in color, consistency, odor, and amount of discharge.

MULTIPLE CAUSES OF ACUTE CERVICITIS Chlamydia trachomatis and Neisseria gonorrhoeae produce varying degrees of acute in ammatory reaction of the glandular epithelium and are common causes of cervicitis, along with M. genitalium, Trichomonas vaginalis, and herpes simplex virus (HSV). Bacterial vaginosis is com- monly associated with cervicitis, even without concurrent vaginal ndings. Other infectious agents, such as rarer bacteria, viruses, fungi, and parasites, have been reported to cause cervicitis, with genital schistosomiasis now coen- demic with HIV in sub-Saharan Africa. 8 Most of the 79 million Americans infected with human papillomavirus (HPV) are unaware of the infection. 9 In a 2013 study by Shen and Liu, patients with mucopurulent cervicitis had high rates (over 50%) of predominantly oncogenic HPV strains 16 and 58, indicating a clear need for close follow-up. 10 Abnormality of vaginal ora (for example, absence of hydrogen peroxide–producing lactobacilli), allergens, or idiopathic in ammation should be considered as causes of cervicitis. Unfortunately, many women are led to believe that menstrual blood and the normal amine odor of vagi- nal discharge is unhealthful and may resort to deodorants, perfumes, or douches. 11,12 Exposure to these irritant chem- icals can disrupt the normal balance of vaginal ora and cause cervicitis.

CLINICAL PRESENTATION Although cervicitis often is asymptomatic, women may present with a change in vaginal discharge, intermenstrual or postcoital bleeding, dyspareunia, pelvic or abdominal pain, and vulvovaginal irritation. Urinary symptoms may be present with concomitant urethral infection. Pain and fever are unlikely in the absence of PID or HSV. FIGURE 1. Some diseases caused by Chlamydia Copyright \251 2018 American Academy of Physician Assistants SPECIAL TOPICS IN WOMEN’S HEALTH 52 www.JAAPA.com Volume 31 Number 2 February 2018 Mucopurulent discharge may be present, and the cervix may be friable, with sustained easy bleeding when gently palpated or swabbed. Diffuse vesicular lesions or ulcer- ations suggest HSV; punctate hemorrhages are character- istic of T. vaginalis. Condyloma lesions may have a at, raised, or cauli ower appearance. On bimanual examina- tion, cervical motion tenderness, caused by in ammation of the pelvic ligaments, is a clear indication of PID. Clinicians also should look for associated, noninfectious causes such as abrasions or ecchymoses.

TESTING AND TREATMENT Subjective and physical ndings usually suggest the cause of acute cervicitis. NAAT assays for gonorrhea and chla- mydia usually con rm diagnosis. 6 Vaginal pH testing for bacterial vaginosis, and the microscopic presence of tricho- monads or the “clue” cells of bacterial vaginosis may be useful. Leukorrhea (more than 10 white blood cells per high-power eld) is highly suspicious for cervicitis. 5 The CDC advises annual STI testing for women under age 25 years and older women with risk factors. 13 Goals of treatment are to relieve symptoms, prevent infection of the upper genital tract, and limit transmission to others. If clinical suspicion is suggestive of C. trachoma- tis or N. gonorrhoeae, initiate empiric therapy. 14 The CDC recommends cover for chlamydia at a minimum.13 If risk or local prevalence is high, or if the patient is pregnant, initiate presumptive treatment for chlamydia and gonor- rhea. 13 PID therapy is usually targeted toward chlamydia (with a macrolide) and gonorrhea (with a cephalosporin). If PID symptoms persist despite treatment attempts, consider eradicating M. genitalium. Because of the diagnostic challenge, and recent reports of 40% macrolide resistance, empiric treatment with moxi oxacin 400 mg daily for 14 days is suggested. 13,15 Tell patients to avoid sexual intercourse until treatment is complete and for 7 days after completing any single-dose regimen. Removal or discontinuation of chemical or mechanical causes should be suf cient for resolution of noninfectious cervicitis. If the condition persists, and tests for malignancy are negative, refer the patient to gynecology. Testing for HIV and syphilis, along with risk reduction counseling, should be part of the visit for any patient presenting with cervicitis.

FOLLOW-UP Tests of cure for chlamydia and gonorrhea are not needed unless symptoms persist or the patient is pregnant. However, because of high rates of reinfection, repeat testing 3 to 6 months after laboratory con rmation of these infections is recommended. 16 This presents an opportunity for further counseling and risk reduction. Liu and colleagues recom- mend regular follow-up for patients with mucopurulent cervicitis, given the predominance of oncogenic strains of HPV in their study. 8 Follow-up should occur at more frequent intervals than those recommended for routine cervical cancer screening.

CONCLUSION Current recommendations for reduced frequency of routine gynecologic screening examinations may increase the risk of missing pathogens such as chlamydia, gonorrhea, or M. genitalium. Incidence of STI in the United States is again rising, and clinicians should take advantage of any oppor- tunity to screen for infection, while being sensitive to the possibility of a patient’s alarm at an unexpected, and sometimes serious, diagnosis. JAAPA REFERENCES 1. Centers for Disease Control and Prevention. Sexually Transmit- ted Disease Surveillance 2016. Atlanta, GA: US Department of Health and Human Services; 2017.

2. Woods JL, Bailey SL, Hensel DJ, Scurlock AM. Cervicitis in adolescents: do clinicians understand diagnosis and treatment?

J Pediatr Adolesc Gynecol. 2011;24(6):359-364. FIGURE 2. Nabothian cyst (left) and cervical polyp (right) Copyright \251 2018 American Academy of Physician Assistants Identifying acute cervicitis in an era of less-frequent routine gynecologic examinations JAAPA Journal of the American Academy of Physician Assistants www.JAAPA.com 53 3. US Preventive Services Task Force. Cervical cancer: screening. https://www.uspreventiveservicestaskforce.org/Page/Document/ UpdateSummaryFinal/cervical-cancer-screening. Accessed October 26, 2017. 4. Johnson LF, Lewis DA. The effect of genital tract infections on HIV-1 shedding in the genital tract: a systematic review and meta-analysis. Sex Transm Dis. 2008;35(11):946-959. 5. Centers for Disease Control and Prevention. Diseases character- ized by urethritis and cervicitis. https://www.cdc.gov/std/tg2015/urethritis-and-cervicitis.htm. Accessed October 26, 2017. 6. Ona S, Molina RL, Diouf K. Mycoplasma genitalium: an overlooked sexually transmitted pathogen in women? Infect Dis Obstet Gynecol . 2016;2016:4513089. 7. Lis R, Rowhani-Rahbar A, Manhart LE. Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis. Clin Infect Dis . 2015;61(3):418-426. 8. Holmen SD, Kleppa E, Lillebø K, et al. The rst step toward diagnosing female genital schistosomiasis by computer image analysis. Am J Trop Med Hyg . 2015;93(1):80-86. 9. Centers for Disease Control and Prevention. Genital HPV infection—fact sheet. https://www.cdc.gov/std/hpv/stdfact-hpv.htm. Accessed October 26, 2017. 10. Shen XH, Liu SH. Human papillomavirus genotypes associated with mucopurulent cervicitis and cervical cancer in Hangzhou, China. Asian Pac J Cancer Prev . 2013;14(6):3603-3606. 11. Mosher WD, Deang LP, Bramlett MD. Community environment and women’s health outcomes: contextual data. Vital Health Stat 23. 2003;(23):1-72. 12. Branch F, Woodruff TJ, Mitro SD, Zota AR. Vaginal douching and racial/ethnic disparities in phthalates exposures among reproductive-aged women: National Health and Nutrition Examination Survey 2001-2004. Environ Health . 2015;14:57. 13. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137. 14. US Department of Health and Human Services. Of ce of Disease Prevention and Health Promotion. Healthy People 2020. https:// www.healthypeople.gov/2020/topics-objectives/topic/sexually-transmitted-diseases. Accessed October 26, 2017. 15. Salado-Rasmussen K, Jensen JS. Mycoplasma genitalium testing pattern and macrolide resistance: a Danish nationwide retrospec-tive survey. Clin Infect Dis . 2014;59(1):24-30. 16. Hosenfeld CB, Workowski KA, Berman S, et al. Repeat infection with chlamydia and gonorrhea among females: a systematic review of the literature. Sex Transm Dis. 2009;36(8):478-489.