Chapter 40. Benign Disorders of the Uterine Cervix

The cervix develops from the paramesonephric (müllerian) ducts in the sixth week of embryologic development. The midline fusion and subsequent canalization of the 2 müllerian ducts give rise to the uterine corpus, cervix, and upper vagina (Fig. 40–1). Müllerian duct anomalies result from nondevelopment, defective lateral or vertical fusion, or resorption failure. The most common type of müllerian fusion defect is a lateral fusion defect in which the resulting defective organs can be either symmetrical or asymmetrical and can be obstructed or unobstructed. These fusion defects result from failure of fusion of the müllerian ducts, failure of formation of 1 müllerian duct, or absorption of the intervening septum. Defective resorption of the tissue between the fused müllerian ducts results in a uterine septum that can be partial or extend to the full length to the cervix. The most common lateral fusion defect is a septum. Vertical fusion refers to the fusion of the müllerian ducts with the urogenital sinus. The absence of müllerian development results in agenesis of the cervix and uterus. A double cervix is frequently associated with a longitudinal vaginal septum and is an example of lack of fusion. A single hemicervix or septate cervix composed of single muscular septum that can be an extension of a lower uterine segment or vaginal septum is seen with resorption failure. Approximately 20–30% of women with müllerian duct anomalies also have urinary tract abnormalities, a finding that warrants urinary tract imaging. Women with müllerian duct anomalies have normal ovaries and develop normal secondary sex characteristics.

Cervical Agenesis

Isolated cervical agenesis is rare, but cases of an absent uterine cervix with a normal uterine corpus and normal vagina have been reported. These cases presumably result from either failure of müllerian duct canalization or abnormal epithelial proliferation after canalization. More common is absence of the cervix combined with absence of the uterine corpus and upper vagina, known as müllerian agenesis or Mayer-Rokitansky-Kuster-Hauser syndrome, which occurs in approximately 1 in 4000 female births. Because most of the vagina is derived from müllerian ducts, the vagina may be shortened in müllerian agenesis. Female offspring of women with müllerian agenesis have been studied to identify a possible genetic contribution to this disorder. Because no offspring with müllerian agenesis have been reported, this disorder is assumed to result from a polygenic multifactorial inheritance pattern.

Cervical agenesis with a normal functioning uterine corpus must be differentiated from müllerian agenesis (Figs. 40–2 and 40–3). In the former, menstrual blood may accumulate within the uterus or result in retrograde flow and development of endometriosis. Thus cervical agenesis is usually diagnosed at menarche when patients present with primary amenorrhea and cyclic abdominopelvic pain. Suppression of menstruation with continuous combined estrogen/progesterone pills may improve the pain-related complaints. Ultrasonography, magnetic resonance imaging (MRI), and laparoscopy can help with the diagnosis by defining the anatomy.

Women without a cervix or without a cervix and uterus cannot carry a pregnancy. Because women have normally functioning ovaries, they can undergo in vitro fertilization with their partner's sperm. Pregnancy is achieved with use of a surrogate woman who carries the pregnancy.

Women with müllerian or cervical agenesis may have a shortened or absent vagina. Nonsurgical treatment to lengthen or create a vagina involves the use of vaginal dilators that are under constant perineal pressure. One example is using a bicycle stool designed by Ingram that facilitates dilator use under constant perineal pressure. The most common surgical approach to correct vagina agenesis is the McIndoe technique to create a neovagina. The Vecchietti operation combines a surgical and nonsurgical approach to creating a neovagina and is performed by laparoscopy. Other surgical options include colonovaginoplasty using a segment of colon and vaginoplasty using skin flaps.

Incomplete MüLlerian Fusion

Congenital uterine anomalies are asymptomatic and thus often are undiagnosed. As with müllerian anomalies in general, these defects arise from agenesis, lateral or vertical fusion defects, or lack of canalization. Complete failure of fusion of the müllerian ducts results in duplication of reproductive structures. One example is uterus didelphys (2 uteri). Uterus bicornuate bicollis (2 cervices) has 2 separate uterine horns, each with a distinct cervix and vagina. The 2 vaginas are separated by a midline, longitudinal septum. If incomplete fusion results in a uterine horn ending blindly, a hematocolpos can develop (Fig. 40–4). Bicornuate uterus and arcuate uterus occur when there is partial or incomplete fusion of the müllerian ducts. In a bicornuate uterus, 2 discrete uterine cavities lead to the same cervix. The arcuate uterus may demonstrate minimal depression of the uterine fundus and is often clinically insignificant.

Women with müllerian fusion defects resulting in uterine anomalies have a higher rate of adverse pregnancy outcome. Premature birth may occur in 15–25%, miscarriage is observed in 25–50%, and malpresentation is similarly common (Fig. 40–5).

Failure of Resorption

Defective resorption of the tissue between the fused müllerian ducts will result in uterine septum formation. The septum consists of fibromuscular tissue and can be either partial or full, extending the length of the uterus (Fig. 40–6). Failure or incomplete resorption of this septum is associated with reproductive and obstetric complications. First- and second-trimester spontaneous miscarriages are common and usually occur between 8 and 16 weeks' gestation. Obstetric complications include premature labor, preterm delivery, malpresentation, intrauterine growth restriction, and lower term birth rate. Approximately 15–25% of spontaneous miscarriages are due to müllerian abnormalities.

If a septate uterus is identified in association with reproductive or obstetric complications, surgical therapy is recommended because it is hypothesized that the septum interferes with placentation. Hysteroscopic resection of the uterine septum improves reproductive outcome in women with recurrent spontaneous miscarriages. Ultrasound, MRI, sonohysterography, and hysterosalpingogram provide information to differentiate a septate uterus from other uterine abnormalities. Combined laparoscopy and hysteroscopy is the most reliable method to accurately differentiate a septate uterus from a bicornuate uterus.

Diethylstilbestrol (DES), a synthetic nonsteroidal estrogen, was used between the 1940s and 1971 to prevent premature birth, miscarriages, and other obstetric complications. Although the number of pregnant women treated with DES is unknown, estimates range from 2–10 million. DES crosses placenta and affects reproductive tract cell differentiation. In utero exposure to DES is also associated with vaginal clear cell carcinoma in female offspring, necessitating cytologic and colposcopic screening. Common structural changes of the cervix include collars, hoods, cockscombs, and pseudopolyps, cervical hypoplasia, and transverse septa (Fig. 40–7). Anomalies of the uterus include a T-shaped uterine cavity, hypoplastic uterus, adhesions, and constrictions of uterine cavity.

Women who are exposed to DES in utero and have cervical abnormalities are at increased risk for infertility. These women are also at increased risk for adverse outcomes in pregnancy, including miscarriage, ectopic pregnancy, and premature delivery. The use of prophylactic cervical cerclage for cervical incompetence related to DES exposure in utero is considered based on standard recommendations for cerclage placement.

Lacerations

Cervical lacerations are frequent complications of a vaginal delivery. With vaginal deliveries, the most common site of cervical lacerations is the lateral aspect of the cervix. Clinically significant lacerations that are associated with vaginal bleeding or that require suturing complicate less than 5% of vaginal deliveries. Cervical cerclage, precipitous labor, vacuum extraction, nulliparity, and episiotomy are associated with increased risk for clinically significant lacerations. Cervical lacerations that cause abnormal vaginal bleeding or that extend to the lower uterine segment or vaginal wall warrant repair. Careful inspection of the entire cervix after delivery enables identification and repair of these clinically significant lacerations. Asymptomatic lacerations that are small may not need repair. Cervical lacerations do not appear to affect the outcome of subsequent pregnancies.

Performance of dilatation and curettage (D&C), particularly on the postmenopausal patient, can result in cervical laceration, most commonly during dilatation. When a tenaculum tears through the cervix with dilatation, it can easily be repaired by suturing, if needed. Use of cervical laminaria preoperatively may decrease the risk of laceration. Preoperative use of misoprostol to soften the cervix and reduce the force required to dilate it has been reported as an additional strategy.

Cervical lacerations are also reported with operative hysteroscopy, with use of the resecting loop, the roller-ball, and other instruments used to ablate the endometrium.

Perforations

Perforation of the cervix may occur inadvertently during sounding of the uterus, cervical dilatation, insertion of radioactive sources, or conization of the cervix or during self-induced abortion with sharp objects (eg, wires or darning or knitting needles). The urinary bladder and the rectum are at risk for injury because of their close proximity to the cervix. Perforations may involve the entire thickness and result in hemorrhage or hematoma if the uterine vessels are involved.

Ulcerations

Ulceration of the cervix may result from pressure necrosis related to vaginal pessary use. Cervical ulceration may also develop in women with complete uterine prolapse whose cervix protrudes through the vaginal introitus.

Cervical Stenosis

Cervical stenosis may lead to significant symptoms. In premenopausal women, cervical stenosis may obstruct menstrual flow, leading to amenorrhea, pelvic pain, and endometriosis. Additionally, cervical stenosis may impede the movement of semen into the uterus and thus be associated with an increased risk of infertility. Pyometra, although uncommon in women with cervical stenosis, is more common in postmenopausal women. Evacuation of pyometra and biopsy of intrauterine contents to rule out endometrial carcinoma is advised.

Although cervical stenosis may be present from birth, it may be caused by other factors. Cervical surgery such as cone biopsy, loop excision, or cryotherapy for treatment of dysplasia may lead to cervical stenosis. Excision by loop diathermy is less likely to cause cervical stenosis than a cold knife cone biopsy, perhaps because less stroma is removed or because suturing performed with cold knife cone may heal occluding the cervical os. Other causes of stenosis are trauma to the cervix, radiation therapy, and cervical cancer. Cervical atrophy with menopause may result in cervical stenosis.

The diagnosis of cervical stenosis is made clinically, by the inability to pass a small cervical dilator. The obstruction of the cervical canal may be suggested by visualizing intrauterine contents on ultrasonography of the uterus. Treatment of cervical stenosis involves opening or widening the cervical canal. The gentle passage of graduated sounds through the cervical canal at weekly intervals during the intermenstrual phase for 2–3 months after treatment will prevent or correct stenosis. In some circumstances, passing dilators under ultrasound guidance may be helpful. If the stenosis is associated with scar tissue, techniques to vaporize the scar tissue with laser treatment or enlarge the canal with loop diathermy and the resecting loop of the hysteroscope may be performed.

Annular Detachment

Annular detachment of the cervix is an extremely rare obstetric complication in which the cervix is devitalized and torn during labor. Proposed mechanisms include previous cervical damage, failure of the external os to dilate, and compromised blood supply by pressure of the fetal head. The diagnosis may be unrecognized or may be made when the detached ring or portion of cervix is expelled during delivery.

Complications of Cervical Injuries

Cervical injuries can result in immediate and delayed complications. Hemorrhage, although uncommon, is the most immediate and serious complication of cervical laceration. When the cervical tear extends into the lower uterine segment, vaginal bleeding may be present, but occult hemorrhage may occur and result in hypovolemic shock out of proportion to visible blood loss.

Cervical stenosis, cervical incompetence, and failure of the cervical dilation during labor are all sequelae of cone biopsy, and less commonly, unrecognized or improperly repaired lacerations. Repeated or habitual abortion, often occurring during the second trimester of pregnancy, may be due to cervical incompetence.

General Considerations

The squamocolumnar junction of the cervix undergoes change over reproductive life. In younger women, the squamocolumnar junction is on the ectocervix. When it extends to replace a large part of the ectocervix, the term cervical ectopy is used, and the cervix appears red, granular and inflamed-appearing. Over time, the squamocolumnar junction moves toward the external os through the process of squamous metaplasia, in which the columnar epithelium on the ectocervix is gradually converted to stratified squamous epithelium. Initially, the metaplastic epithelium is thin and immature, but it becomes thicker and more mature, eventually becoming stratified squamous epithelium. Microscopically, the squamocolumnar junction rarely demonstrates an abrupt transition from squamous to columnar epithelium, but instead has a zone of immature squamous metaplasia (Figs. 40–8 and 40–9). On colposcopy, cervical ectopy has a fine villiform pattern (Figs. 40–10 and 40–11). This change from a mucous membrane of a single layer of columnar epithelium to one of the stratified squamous epithelium may be accelerated during 3 periods of a woman's life: fetal existence, adolescence, and during the first pregnancy.

By the time a woman reaches her fifth decade, the squamocolumnar junction has receded into the endocervical canal, and the ectocervix is completely covered by squamous epithelium. In the process, the crypts and clefts of columnar epithelium are bridged over and may be occluded, obstructing the egress of mucus, producing the common, typical nabothian cysts of the cervix.

General Considerations

Annually 3 million women are diagnosed with cervicitis. Most common causes of infectious cervicitis are Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus (HSV), human papillomavirus (HPV), and trichomoniasis, Mycoplasma genitalium, cytomegalovirus, and bacterial vaginosis (covered in Chapter 43). Cervicitis often is asymptomatic and may be undiagnosed for some time. If untreated, cervicitis can result in pelvic inflammatory disease and ultimately lead to a higher risk of infertility, ectopic pregnancy, and chronic pelvic pain. Advances in colposcopy and sensitive testing for infectious diseases have allowed better assessment of the causes of acute and chronic cervicitis. Methods for testing gonorrhea include urethral Gram stain, culture on Thayer-Martin media, DNA probes, and DNA amplification techniques. Testing for chlamydia can be performed using nucleic acid amplification techniques on cervical or urine specimens. For HPV infection, cervical cytology (Pap test) and HPV testing are used with colposcopy and biopsy for detection of HPV disease. The signs of cervicitis are caused by edema and increased vascularity, making the cervix appear swollen and reddened. The presence of hypervascularity, erythema, and ectopy may be found with either squamous metaplasia or inflammatory changes requiring therapy. Cervicitis can be diagnosed histologically when polymorphonuclear leukocytes, lymphocytes, or histiocytes are noted. The cervix is in direct contact with the vagina and is exposed to viral, bacterial, fungal, and parasitic agents. Cervical infections occur in the absence of vaginal disease. Through sexual contact, the cervix may be infected with N gonorrhoeae, C trachomatis, HSV, HPV, and Mycoplasma spp. Because many women are asymptomatic, screening women in high-risk populations such as those with multiple partners and those with inconsistent use of condoms is important. Patients diagnosed with gonorrhea or chlamydia are at risk for infection with other sexually transmitted diseases (STDs). Counseling and testing should be offered for syphilis, hepatitis B, and HIV, as well as testing for HPV.

Pathogenesis

C trachomatis and N gonorrhoeae are sexually transmitted infections (STIs) commonly causing endocervicitis as well as upper reproductive tract infections. More than 1.1 million cases of C trachomatis and 350,000 cases of N gonorrhoeae were reported in United States in 2007. As C trachomatis is often “silent,” an undiagnosed, ongoing infection may ascend into the endometrial cavity to the fallopian tubes, causing salpingitis as well as pelvic peritonitis. With the cervix as a reservoir, the organism may infect the fetus during its passage through the birth canal. C trachomatis transmitted to the eyes causes trachoma and inclusion conjunctivitis or pneumonia of the newborn.

As with Chlamydia infections, N gonorrhoeae first causes a cervical infection, which may ascend infecting the endometrium and fallopian tubes. The ascending infection for either agent may occur at the end of menses when there is no protective mucus plug. As with C trachomatis,N gonorrhea can be transmitted to newborns during vaginal delivery, causing neonatal ophthalmia.

Fitz-Hugh-Curtis syndrome or perihepatitis is a rare complication usually caused by C trachomatis and N gonorrhoeae and is characterized by adhesions between the liver and the parietal peritoneum.

There are 2 types of HSV, herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). Although HSV-2 causes most of the genital herpes infections, HSV-1, the etiology of the common cold sore or fever blister, causes some through oral–genital or genital–genital contact. HSV infection produces cervical lesions similar to those found on the vulva. First the lesion is vesicular and then becomes an ulcer. Primary infections may be extensive and severe, producing constitutional symptoms of low-grade fever, myalgia, and malaise lasting approximately 2 weeks. The ulcers heal without scarring. Once infection has occurred, even after healing, the virus continues to reside in the nerve cells of the affected area for life. HSV recurrences are less severe in both symptoms and duration. HSV is found in the lesions caused by HSV infection, but viral shedding can also occur in asymptomatic patients without obvious lesions. Women with either active infection or asymptomatic HSV shedding from normal-appearing skin can infect their infants during vaginal delivery. Those with a positive HSV test near term are advised to undergo caesarean section.

HPV is spread by skin-to-skin contact. Women with vulvar HPV lesions should be assessed for cervical HPV lesions and infection. The cervical lesions are flatter than typical genital warts (condylomata acuminata) seen on the vulva and perianal skin. In fact, they often are invisible to the naked eye, becoming visible only after application of a dilute solution of acetic acid (acetowhite epithelium) or by colposcopic examination (white epithelium, mosaicism, and coarse punctation). There are more than 120 HPV types. Low-risk types 6, 11, 42, 43, 44, 54, and 55 are associated with benign lesions of the cervix, whereas types 16, 18, 31, 33, 35, 39, 45, and 56 are considered high risk and found in association with cervical intraepithelial neoplasia and invasive cancers. Seventy percent of infections resolve in 1 year and 90% by 2 years. Persistent HPV infection may progress to precancerous lesions and, over time, progress to cervical cancer.

Prevention

Abstinence and the use of condoms and barrier methods for protection during coitus are the most important strategies for prevention of cervicitis. Although avoiding sexual contact with infected persons is a sound recommendation, most women do not know whether their partner(s) have an STI, and many of these partners, if infected, are asymptomatic. Because chlamydia and gonorrhea are most prevalent in young adults aged 19 to 25 and have significant long-term complications, annual screening for these 2 infections is advised in high-risk populations, regardless of whether they have symptoms. Other “at risk” populations include those having multiple sexual partners, inconsistently using condoms, with a previous history of STIs, and individuals who engage in other high-risk behaviors (eg, current or prior drug abusers); however, these different risk factors may be difficult to assess.

Because asymptomatic patients are at similar risk of developing complications as symptomatic women, detecting infection in asymptomatic patients is also important.

Treating affected partners at the same time the woman is treated is important to prevent reinfection. Counseling patients and her sexual partner(s) may also be useful.

Detection and treatment of cervicitis in pregnancy has important health benefits for the fetus and newborn. For example, pregnant women should be screened for syphilis and HIV at the first prenatal visit (see Chapter 43). Women with a history of HSV should be screened near term (see Chapter 43). Women at high risk of premature delivery should be screened for bacterial vaginosis (see Chapter 43).

The prompt recognition and proper repair of cervical lacerations lessen the risk of cervical stenosis and cervical incompetence in future pregnancies.

When hysterectomy is performed, if possible, the cervix should be removed to minimize the risk of cervical diseases. Although some recommend retaining the cervix at the time of hysterectomy to maintain sexual function or vaginal support, clinical studies do not provide evidence to support this recommendation.

Clinical Findings

Symptoms & Signs

Acute Cervicitis

Purulent vaginal discharge is the primary sign and symptom of acute cervicitis. Some women have vaginal bleeding, most frequently after sexual intercourse, although intermenstrual bleeding and bleeding during examination can also occur. The appearance of the discharge varies depending on the pathogen—often thick and creamy discharge is noted in gonorrheal infection, foamy and greenish-white in trichomonal infection, white and curd-like in candidiasis, and thin and gray in bacterial vaginosis. In bacterial vaginosis, an amine or fishy odor is released when the discharge is combined with potassium hydroxide. Vulvar burning and itching may be prominent symptoms of cervicitis.

Chlamydia infections may produce a purulent discharge from a reddened, congested cervix or may be relatively asymptomatic, without visible signs. The muculopurulent discharge of chlamydia infection is often indistinguishable from that of gonorrheal infection. On inspection, the cervix infected by N gonorrhoeae reveals an acutely inflamed and edematous cervix with a purulent discharge from the external os. In trichomonal infection, a strawberry-like appearance covers the ectocervix and may extend to the adjacent vaginal mucosa. In candidiasis, a white cheesy exudate may be difficult to wipe away and once wiped off usually leaves punctate hemorrhagic areas.

Gonorrheal or chlamydial cervicitis may be accompanied by urethritis with frequency, urgency, and dysuria. If any infection is associated with acute salpingitis, the symptoms and signs will include pelvic peritonitis. Postcoital bleeding or intermenstrual spotting may occur because of hyperemia of the infected cervix associated with freely bleeding areas. Cervical friability with bleeding occurs when endocervical smears are obtained.

Colposcopic findings of acute cervicitis reveal an altered microangioarchitecture with marked increase in the surface capillaries, which when viewed end-on may show a pattern of diffuse “punctation.” Trichomoniasis is typified by characteristic double-hairpin capillaries. In an inflammatory process, the colposcopic picture is diffuse with ill-defined margins in contrast with the localized and sharply demarcated vascular changes associated with intraepithelial neoplasia (Chapter 48). Invasive cancers may be secondarily infected, so in addition to the colposcopic changes associated with malignancy, those related to inflammation are also present.

Chronic Cervicitis

In chronic cervicitis, leukorrhea may be the chief symptom. Although not as profuse as in acute cervicitis, the discharge may cause vulvar irritation. The discharge may be frankly purulent and variable in color, or may simply be thick, tenacious, turbid mucus. Intermenstrual or postcoital bleeding may occur. Associated symptoms may be lower abdominal pain, lumbosacral backache, dysmenorrhea, dyspareunia, urinary frequency, urgency, and dysuria.

Inspection of the chronically infected cervix often reveals only abnormal discharge, with the upper vagina appearing normal.

Laboratory Findings

Stains and Smears

Mucopurulent cervicitis is defined as evidence of purulent material on inspection of an inflamed cervix along with 10 or more polymorphonuclear leukocytes per high-powered microscopic field seen on Gram's stain of the discharge. In acute cervicitis with N gonorrhoeae, the sensitivity of Gram's stain for detection of diplococci is only 50%. Thus use of Gram's stain for diagnosis is not recommended in women because of its low sensitivity in detecting infection. Identification of motile flagellated organisms on saline wet smear preparations suggests Trichomonas vaginalis. In symptomatic patients, with signs suggesting Trichomonas, further testing of nucleic acid amplification, culture testing may be necessary. Bacterial vaginosis can be seen on saline wet mount by the coating of epithelial cells with bacteria called “clue cells.” Bacterial vaginosis is diagnosed by using Amsel criteria: thin homogeneous white, yellow discharge, presence of the “clue cells” on microscopy, vaginal pH >4.5, and fishy odor on adding alkaline 10% potassium hydroxide solution. Presence of 3 of these criteria will confirm the diagnosis of bacterial vaginosis. Candidal infections can be seen on potassium hydroxide preparations, with the distinctive presence of hyphae.

Detection of Specific Agents Causing Cervical Infections

Previously, culture was the preferred method to detect infection. N gonorrhoeae culture is performed on Thayer-Martin or blood agar medium. Although culture has excellent specificity, the sensitivity is no higher than 70% in females. Culture can be influenced by how the specimen was collected, transport conditions, culture procedures, and identification of a positive culture.

More recently, infection is detected more reliably with nucleic acid amplification methods such as polymerase chain reaction (PCR), transcription-mediated amplification, and strand displacement amplification. The benefit of using nucleic acid amplification is its high sensitivity and specificity (82–100%). The specimen can be obtained noninvasively from either a vulvar swab or urine, with non–clean catch urine specimens having greater sensitivity than cervical testing. These tests also allow for simultaneous detection of both N gonorrhoeae and C trachomatis from the same specimen. Sensitivity with urine and cervical samples is similar for C trachomatis, but sensitivity for N gonorrhoeae is higher with cervical swab. Enzyme immunoassay and direct fluorescent antibody rely on antigen detection and have a sensitivity ranging from 70–80%, but the specimen still requires invasive testing using a swab from the cervix or urethra.

HSV infection can be detected by viral culture, PCR, and direct fluorescence antibody. Most laboratories are moving toward nonculture assays such as PCR, which offer high sensitivity and specificity.

Syphilis is detected by using nontreponemal rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) tests and subsequent confirmation with microhemagglutination assay for Treponema pallidum (MHA-TP), fluorescent treponemal antibody-absorption (FTA-ABS) tests.

Combining HPV testing with cervical cytology appears to be the most effective strategy for detecting abnormal cervical pathology. Cervical cytology with HPV testing is first performed in women at 21 years of age regardless of the age of onset of sexual activity because of the low risk of cancer in women under age 21. If cytology is normal and HPV testing is negative, follow-up screening is done in 3 years. If cytology is abnormal, colposcopy with directed biopsy is advised.

Blood Studies

In uncomplicated cervicitis not accompanied by salpingitis, the white count may be normal. With salpingitis, a leukocytosis is common with an elevated white count. The erythrocyte sedimentation rate may be slightly elevated.

Cytopathology

Until recently, the Papanicolaou (Pap) smear has been the primary tool to examine the pathologic changes related to cervical neoplasia. Cellular changes of mild dysplasia (low-grade squamous intraepithelial lesion [SIL]), moderate or severe dysplasia (carcinoma in situ [CIS], high-grade SIL), and invasive cancer may be delineated on cytology testing.

Epithelial cell changes associated with cervical inflammation may be difficult to distinguish from those related to neoplastic disease. Nuclear enlargement, clumping of chromatin, hyperchromatism, and nucleoli, as well as cytoplasmic eosinophilia and poorly defined cell membranes, are nonspecific findings of “cytologic atypia.” A few inflammatory cells can be seen on the cytology slide, particularly immediately before, during, and immediately after menses. However, large numbers of polymorphonuclear leukocytes or histiocytes indicate an acute cervicitis. When the inflammatory cells are so dense that the epithelial cells are obscured, the smear should be repeated after the inflammatory process has been treated.

Cervical cytology evaluation can also aid in the diagnosis of specific cervical infections. At times, a specific diagnosis can be made either by identifying the infectious organism(s) or by noting changes in the epithelial cells characteristic of a specific type of infection. For example, trichomonads and yeast forms can be identified directly on cytology slides. HPV infection is characterized by squamous epithelial cell enlargement, multinucleation, and the perinuclear “halo” effect of koilocytosis. Enlarged, multinucleated cells with ground-glass cytoplasm and nuclei containing inclusion bodies are indicative of HSV infection.

Histopathology of Cervical Infections

Both N gonorrhoeae and C trachomatis infections produce a nonspecific acute inflammatory reaction of edema and increased vascularity, and the cervix becomes swollen and reddened. Gross appearance of acute cervicitis must be distinguished clinically and histologically from cervical ectopy. Infection causes the glandular epithelium to hyperfunction, producing a copious purulent or mucopurulent exudate and mucus mixed with inflammatory cells. Microscopically, stromal edema and infiltration by polymorphonuclear leukocytes are seen, and some mucous membrane may be denuded. As the acute infection subsides, swelling and redness disappear, and polymorphonuclear leukocytes are replaced by lymphocytes, plasma cells, and macrophages—the histologic picture of chronic cervicitis. Almost all parous women may have findings characteristic of chronic cervicitis on biopsy that are not significant unless they also have clinical signs and symptoms of cervicitis.

Differential Diagnosis

Noninfectious cervicitis may result from the effects of endogenous or exogenous hormones on the cervicovaginal mucosa. When cervical discharge is noted, bimanual examination may aid in diagnosis of pelvic infection with the clinical signs of cervical motion tenderness and induration.

Infectious cervicitis must be distinguished from cervical intraepithelial neoplasia. This may be hampered because inflammatory conditions may also result in epithelial atypia on cytologic examination. Colposcopy is a useful adjunct (see Chapter 48). Cervical cytology and histologic examination by endocervical curettage and biopsy may help distinguish chronic cervicitis from cervical neoplasia.

Complications

N gonorrhoeae or C trachomatis cervicitis is often complicated by salpingitis and pelvic inflammatory disease, which are associated with an increased risk of infertility, ectopic pregnancy, and chronic pelvic pain. The occurrence of gonorrheal or chlamydial cervicitis in HIV-infected women has been reported to be associated with increased shedding of HIV-1 that, in turn, increases the infectiveness of these women. Although a history of genital infections is more common among women with carcinoma of the cervix, these agents do not increase the risk of developing cancer.

Treatment

Selecting the treatment for cervicitis depends on the nature of the infection, whether the patient is pregnant or breastfeeding, her plans for future pregnancy, the severity of the cervical infection as indicated by the presence or absence of complicating factors such as salpingitis, and previous treatment. Instrumentation should be avoided during the acute cervicitis to minimize the risk of ascending infection.

Acute Cervicitis

Treatment of acute cervicitis is directed at diagnosing a specific organism; treatment is then directed accordingly.

Trichomoniasis

Metronidazole is used to treat T vaginalis infection. Metronidazole can be administered as 2 g orally in a single dose or tinidazole 2 g orally in a single dose, or alternatively as metronidazole 500 mg twice daily for 7 days. Any of these regimens have cure rates of approximately 90–95%. Patients should be advised not to use alcohol during treatment. Abstinence from alcohol should continue for 24 hours after treatment with metronidazole and for 72 hours after using tinidazole. Pregnant women should be given 2 g orally as a single dose; those who are breastfeeding should stop breastfeeding for 12–24 hours. Sex partners should be treated and intercourse should be avoided until women and their sex partners are cured. Topical forms of metronidazole are less efficacious (<50%) than the oral preparations.

Candidiasis

Candidiasis is most effectively treated with topically applied azole drugs. This will result in relief of symptoms. Treatment course may be 1, 3, or 7 days, depending on the severity of infection. Effective treatments include butoconazole 2% cream 5 g intravaginally for 3 days, clotrimazole 1% cream 5 g intravaginally for 7–14 days, clotrimazole 100 mg vaginal tab for 7 days, miconazole 25 cream 5 g intravaginally for 7 days, miconazole 200-mg vaginal suppository for 3 days or 100 mg for 7 days. A single dose of 150 mg fluconazole by mouth is an effective treatment.

Bacterial Vaginosis

See Chapter 43, Sexually Transmitted Diseases and Pelvic Infections.

C Trachomatis

C trachomatis can be treated with azithromycin 1 g orally in a single dose or alternatively with doxycycline 100 mg twice daily for 7 days. Alternative treatments with erythromycin base 500 mg orally 4 times a day for 7 days, erythromycin ethylsuccinate 800 mg orally 4 times a day for 7 days or ofloxacin 300 mg orally twice a day for 7 days, or levofloxacin 500 mg orally once a day for 7 days are suggested. In pregnancy, azithromycin 1 g orally in a single dose or amoxicillin 500 mg orally 3 times a day for 7 days can be given; alternatively erythromycin could be used as well. Doxycycline, ofloxacin, and levofloxacin are contraindicated in pregnancy. Because of the high rate of coinfection with N gonorrhoeae and C trachomatis (up to 42%), when N gonorrhoeae infection is found, it is recommended that patients also receive treatment for C trachomatis.

N Gonorrhoeae

Cervicitis due to N gonorrhoeae can be treated with ceftriaxone 125 mg administered intramuscularly in a single dose, cefixime 400 mg orally in a single dose, ciprofloxacin 500 mg orally in a single dose, or ofloxacin 400 mg or levofloxacin 250 mg orally in a single dose. In pregnancy, fluoroquinolones should be avoided. Fluoroquinolones also should not be used in patients residing in or who may have acquired infections in Europe, Middle East, Asia, the Pacific (including Hawaii), or California because of increasing quinolone-resistant N gonorrhoeae (QRNG) in these areas (see Chapters 43 and 44 and the 2006 Centers for Disease Control and Prevention guidelines for treatment of STDs for full recommendations).

Chronic Cervicitis

Several studies have demonstrated that microscopic findings of 10 or more polymorphonuclear leukocytes per high-power field do not correlate with specific infection using more sensitive testing for N gonorrhoeae and C trachomatis. Therefore, an asymptomatic patient with chronic cervicitis who does not test positive for an STD does not need to be treated.

Surgical procedures may be useful for treatment of symptomatic chronic cervicitis, especially in the absence of an infectious pathogen or evidence of dysplasia. Cryosurgery, electrocauterization, and laser therapy have been used, although there is a high risk for recurrence and risk for cervical injury.

Treatment of Complications

Cervical Hemorrhage

Cervical hemorrhage after surgical procedures such as cone biopsy, electrocauterization, loop excision, cryosurgery, or laser vaporization requires suture ligation of bleeding vessels. For less severe bleeding, directed topical coagulation of bleeding areas with Monsel's solution or silver nitrate is successful. Electrocauterization may also be beneficial.

Salpingitis

Inflammation of the fallopian tubes usually necessitates the administration of a broad-spectrum antibiotic. Intravenous administration may be advised to obtain adequate antibiotic levels.

Leukorrhea

Persistent cervical discharge after treatment may indicate either persistent infection or reinfection. Testing should be performed and selective antibiotic treatment administered.

Cervical Stenosis

Cervical surgery is a common cause of cervical stenosis and secondary amenorrhea after the surgical procedure suggests cervical stenosis. Inability to insert a 2.5-mm diameter dilator is consistent with cervical stenosis. Cervical stenosis is treated by dilating the cervical canal.

Infertility

Normally, midcycle cervical mucus enhances transportation of sperm through the cervical canal. Factors that influence production of normal cervical mucus could have an impact on fertility. They include surgical factors (cauterization, freezing, or vaporization) or removal (conization or loop excision) of the endocervical glandular cells and cervical infections. Treatment includes low-dose estrogen for 1 week before ovulation or intrauterine insemination with washed and incubated sperm.

Tuberculosis, tertiary syphilis, and granuloma inguinale rarely present as chronic cervical lesions. When present, cervical nodules, ulcerations, or granulation tissue may produce a chronic inflammatory exudate characterized histologically by lymphocytes, giant cells, and histiocytes. The gross appearance of the cervix may be difficult to distinguish from carcinoma of the cervix.

Tuberculosis

Since 1986, the incidence of tuberculosis in the United States has increased, particularly among African Americans, Hispanics, and Asians. Some of the increase has been attributed to the HIV epidemic. In the past, genital tuberculosis has accounted for only 1% of patients with pelvic inflammatory disease; however, in European and Asian countries, the occurrence ranges from 5–13%. With increasing numbers of immigrants to the United States and with the rise in incidence of AIDS in American women, an increase in the incidence of pelvic tuberculosis may occur. Genitourinary tuberculosis is commonly secondary to infection elsewhere in the body, usually pulmonary, but active pulmonary disease can be documented in only one-third of patients. Vascular dissemination is responsible for infection of the fallopian tubes in almost all patients with genital tuberculosis, and involvement of the endometrium follows in 90%. Cervical disease can occur by direct extension or lymphatic spread but is rare, occurring in only 1% of cases. The chief clinical manifestations of pelvic and cervical involvement are abdominal pain, irregular bleeding, and constitutional symptoms. The cervix may be hypertrophied and nodular, without any visible lesion. Speculum examination may demonstrate either an ulcerative or a papillary lesion, thus resembling neoplastic disease.

The diagnosis of tuberculosis of the cervix must be made by biopsy. Histologically, the disease is characterized by tubercles undergoing central caseation. Because such lesions may be caused by other entities such as amoebiasis, schistosomiasis, brucellosis, tularemia, sarcoidosis, and foreign body reaction, the tubercle bacillus must be demonstrated by acid-fast stains or culture.

The reader is referred to other texts for the details of medical therapy of genital tuberculosis. Most patients are cured by medical management alone. Patients who respond poorly or who have other problems (eg, tumors, fistulas) may require total hysterectomy and bilateral salpingo-oophorectomy after a trial of chemotherapy.

Lymphogranuloma venereum, a chlamydial infection, and chancroid, caused by Haemophilus ducreyi, may attack the cervix along with other areas of the reproductive tract.

Cervical actinomycosis may occur as a result of contamination by instruments and by intrauterine devices. The cervical lesion may be a nodular tumor, ulcer, or fistula. Prolonged penicillin or sulfonamide therapy is recommended.

Schistosomiasis of the cervix is secondary to involvement of the pelvic and uterine veins by the blood fluke Schistosoma haematobium. Cervical schistosomiasis may produce a large papillary growth that ulcerates and bleeds on contact, resembling cervical cancer. In other instances, Schistosomiasis may be found in endocervical polyps and be associated with intermenstrual and postcoital bleeding. An ovum occasionally can be identified in a biopsy specimen taken from the granulomatous cervical lesion. However, the diagnosis usually is made by recovering the parasite from the urine or feces. Chemical, serologic, and intradermal tests for schistosomiasis are available.

Echinococcal cysts may involve the cervix. Treatment consists of surgical excision.

Nabothian Cysts

Nabothian cysts develop when a cleft or tunnel of columnar endocervical epithelium becomes covered by squamous metaplasia. They appear grossly as translucent or yellow and may vary in diameter from a few millimeters to 3 cm.

Mesonephric Cysts

Microscopic remnants of the mesonephric (wolffian) duct are often seen deep in the lateral vaginal fornices externally in the normal cervix. Occasionally they become cystic, forming structures up to 2.5 mm in diameter, lined by cuboid epithelium. They may be confused with deeply situated nabothian cysts, but their location and the wolffian-type cells lining the cysts serve as useful distinguishing features.

Cervical Polyps

Essentials of Diagnosis

• Intermenstrual or postcoital bleeding
• A soft, red pedunculated protrusion from the cervical canal at the external os
• Microscopic examination confirms the diagnosis of benign polyp

General Considerations

Cervical polyps are small, pedunculated, often sessile neoplasms of the cervix. Most originate from the endocervix; a few arise from the portio (Fig. 40–12). They are composed of a vascular connective tissue stroma and are covered by columnar, squamocolumnar, or squamous epithelium. Polyps are relatively common, especially in multigravidas over 20 years of age. They are rare before menarche, but an occasional polyp may develop after menopause. Asymptomatic polyps often are discovered on routine pelvic examination. Most are benign, but all should be removed and submitted for pathologic examination because malignant change may occur. Moreover, some cervical cancers present as a polypoid mass.

Polyps arise as a result of focal hyperplasia of the endocervix. Whether this is due to chronic inflammation, an abnormal local responsiveness to hormonal stimulation, or a localized vascular congestion of cervical blood vessels is not known. They are often found in association with endometrial hyperplasia, suggesting that hyperestrogenism plays a significant etiologic role. Most polypoid structures are vascular, often are infected, and are subject to displacement or torsion. Increased discharge and postcoital bleeding are common symptoms.

Endocervical polyps usually are red, flame-shaped, fragile growths. The polyps vary from a few millimeters in length and diameter to larger tumors 2–3 cm in diameter and several centimeters long. These polyps usually are attached to the endocervical mucosa near the external os by a narrow pedicle, but occasionally the base is broad. On microscopic examination, the stroma of a polyp is composed of fibrous connective tissue containing numerous small vessels in the center. There is often extravasation of blood and marked infiltration of the stroma by inflammatory cells (polymorphonuclear neutrophils, lymphocytes, and plasma cells). The surface epithelium resembles that of the endocervix, varying from typical picket-fence columnar cells to areas that show squamous metaplasia and mature stratified squamous epithelium. The surface often has many folds, as is much of the normal endocervical mucosa.

Ectocervical polyps are pale, flesh-colored, smooth, and rounded or elongated, often with a broad pedicle. They arise from the outer cells of the cervix and are less likely to bleed than endocervical polyps. Microscopically, ectocervical polyps are more fibrous than endocervical polyps, with few or no mucus glands, and are covered by stratified squamous epithelium.

Metaplastic alteration of both types of polyp is common. Inflammation, often with necrosis at the tip (or more extensively), is typical of both polyp types.

The incidence of malignant change in a cervical polyp is estimated to be <1%. Squamous cell carcinoma is the most common type of malignancy, although adenocarcinomas have been reported. Endometrial cancer may involve the polyp secondarily. Sarcoma rarely develops within a polyp.

Botryoid sarcoma, an embryonal rhabdomyosarcoma tumor of the cervix (or vaginal wall) resembling small pink or yellow grapes, contains striated muscle and other mesenchymal elements. It is extremely malignant.

Because polyps are a potential focus of cancer, they must be examined routinely for malignant characteristics upon removal.

Clinical Findings

Symptoms & Signs

Intermenstrual or postcoital bleeding is the most common symptom of cervical polyps. Leukorrhea (white or yellow mucous secretion) and menorrhagia have also been associated with cervical polyps.

Abnormal vaginal bleeding is often reported. Postmenopausal bleeding is frequently described by older women. In the setting of infertility, it is reasonable to remove them as a potential contributing factor.

Cervical polyps appear as smooth, red, fingerlike projections from the cervical canal. They usually are approximately 1–2 cm in length and 0.5–1 cm in diameter. Generally they are too soft to be felt by the examiner's finger.

X-Ray Findings

Polyps high in the endocervical canal may be demonstrated by hysterosalpingogram or saline infusion sonohysterography.

Laboratory Findings

Vaginal cytology will reveal signs of infection and often mildly atypical cells. Blood and urine studies are not helpful.

Special Examination

A polyp high in the endocervical canal may be seen with the aid of a special endocervical speculum or by hysteroscopy. Some polyps are found only at the time of diagnostic D&C in the investigation of abnormal bleeding.

Differential Diagnosis

Masses projecting from the cervix may be polypoid but are not necessarily polyps. Adenocarcinoma of the endometrium or endometrial sarcoma may present as a mass at the external os or extending beyond. Discharge and bleeding usually occur.

Typical polyps are easy to diagnose by gross inspection, but ulcerated and atypical-appearing growths must be distinguished from other small submucous pedunculated myomas or endometrial polyps arising low in the uterus. Any of these growths may result in dilatation of the cervix, presenting just within the os and resembling cervical polyps. Products of conception, usually decidua, may push through the cervix and resemble a polypoid tissue mass, without other signs and symptoms of pregnancy. Condylomata, submucous myomas, and polypoid carcinomas are diagnosed by microscopic examination.

Complications

Cervical polyps may be infected, some by virulent staphylococci, streptococci, or other pathogens. Serious infections occasionally follow instrumentation for the identification or removal of polyps. A broad-spectrum antibiotic should be administered at the first sign or symptom of spreading infection.

Acute salpingitis may be initiated or exacerbated by polypectomy.

It is unwise to remove a large polyp and then perform a hysterectomy several days later. Pelvic peritonitis may complicate the latter procedure. A delay of several weeks or 1 month between polypectomy and hysterectomy is recommended.

Treatment

Medical Measures

Appropriate testing for cervical discharge should be performed as indicated and treatment administered if infection is identified.

Specific Measures

Most polyps can be removed in the physician's office. The base of the polyp is grasped with forceps and twisted until the growth is avulsed, usually causing little bleeding. When performing polypectomy it is important to cauterize its base to reduce the chances of the bleeding and to decrease the recurrence rate. Large polyps and those with sessile attachments may require excision in an operating room to allow for administration of anesthesia, use of a hysteroscope, and control of any bleeding.

If the cervix is soft, patulous, or definitely dilated and the polyp is large, hysteroscopy should be performed, especially if the pedicle is not readily visible. Exploration of the cervical and uterine cavities with the hysteroscope allows for further identification of other polyps. All tissue must be sent to a pathologist to be examined for possible underlying malignant or premalignant conditions.

Prognosis

Removal of simple, solitary cervical polyps is usually curative.

Papillomas of the Cervix

Essentials of Diagnosis

• Asymptomatic
• Papillary projection from the exocervix
• The presence of koilocytes with or without cytologic atypia
• Colposcopic identification

General Considerations

Cervical papillomas are benign neoplasms found on the ectocervix. The neoplasms consist of 2 types: (1) The typical solitary papillary projection from the exocervix composed of a central core of fibrous connective tissue covered by stratified squamous epithelium. This is a true benign neoplasm, and the cause is unknown. (2) Condylomata of the cervix, which may be present in various forms ranging from a slightly raised area on the exocervix that appears white after acetic acid application (on colposcopy) to the typical condyloma acuminatum. These usually are multiple and are caused by HPV infection, an STD. Similar lesions of the vagina and vulva are often, but not always, present. Evidence of HPV infection can be found in 1–2% of cytologically screened women. The incidence is much higher in women attending STD clinics.

Prevention

Contraception with condoms and other barrier methods may prevent primary infection and reinfection.

Clinical Findings

Symptoms & Signs

There are no characteristic symptoms of cervical papillomas; they are often discovered on routine pelvic examination or colposcopic examination for dysplasia revealed by Pap smear.

Laboratory Findings

Cytologic findings of koilocytes—squamous cells with perinuclear clear halos—are strongly suggestive of HPV infection. Dysplastic squamous cells are frequently found in association with koilocytes. HPV type testing of cervical or vaginal secretions may be used to determine whether there are oncogenic risk types. Biopsy of involved epithelium reveals papillomatosis and acanthosis. Mitoses may be frequent, but in the absence of neoplastic change, the cells are orderly with regular nuclear features. Koilocytes predominate in the superficial cells.

Complications

Intraepithelial neoplasia is associated with certain types of HPV infection (see Cervical Intraepithelial Neoplasia, Chapter 48). Infection with HPV anywhere in the genital tract, vulva, vagina, or cervix increases the risk of developing squamous cell carcinoma of the cervix.

Treatment

Solitary papillomas should be surgically excised and submitted for pathologic examination. Likewise, colposcopically directed biopsies of flat condylomata should be submitted for histopathologic examination. Flat condylomata may be completely removed with a biopsy instrument if they are small. More extensive lesions may require cryotherapy, loop excision, or laser vaporization. Dysplasia associated with HPV infection should be managed according to the severity and extent of the dysplastic process (see Cervical Intraepithelial Neoplasia, Chapter 48).

Prognosis

Because the entire lower genital tract is a target area for HPV infection, long-term follow-up with attention to the cervix, vagina, and vulva is necessary.

Leiomyomas of the Cervix

The paucity of smooth muscle elements in the cervical stroma makes leiomyomas that arise in the cervix uncommon. The corpus leiomyoma/cervical leiomyoma ratio is in the range of 12:1.

Although myomas usually are multiple in the corpus, cervical myomas are most often solitary and may be large enough to fill the entire pelvic cavity, compressing the bladder, rectum, and ureters (Fig. 40–13). Grossly and microscopically they are identical to leiomyomas that arise elsewhere in the uterus.

Clinical Findings

Symptoms & Signs

Cervical leiomyomas are often silent, producing no symptoms unless they become very large. Symptoms result from pressure on surrounding organs such as the bladder, rectum, or soft tissues of the parametrium, or obstruction of the cervical canal. Frequency and urgency of urination are the result of bladder compression. Urinary retention occasionally occurs as a result of pressure against the urethra. Heavy vaginal bleeding may occur. Hematometra may develop with obstruction of the cervix.

If the direction of growth is lateral, there may be ureteral obstruction with hydronephrosis. Rectal encroachment causes constipation. Dyspareunia may occur if the tumor occupies the vagina. Large cervical leiomyomas in pregnancy, because of their location, unlike those involving the corpus, may cause soft-tissue dystocia, preventing descent of the presenting part in the pelvis. Cervical leiomyomas of significant size can be readily palpated on bimanual examination.

Imaging

A plain film may demonstrate the typical mottled calcific pattern associated with cervical leiomyomas. Hysterography may define distortion of the endocervical canal. Intravenous urography may demonstrate ureteral displacement or obstruction. Transvaginal ultrasound or MRI can be helpful in determining the size and location.

Treatment

Small, asymptomatic cervical leiomyomas do not require treatment. If the leiomyomas become symptomatic, removal may be possible via hysteroscopic resection. If additional multiple leiomyomas are present that cannot be resected with the hysteroscope, uterine artery embolization, abdominal myomectomy, or hysterectomy may be indicated, depending on the patient's desire for preservation of fertility.

Because of the proximity of the pelvic ureter to the cervix, the ureter is at risk of damage in operation involving a cervical leiomyoma. Dissecting the ureters or placement of stent may prevent its injury.

Prognosis

Recurrence of cervical myomas after surgical removal is rare.