Porth's Essentials of Pathophysiology, 4e

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Genitourinary and Reproductive Function

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pregnancy and prolonged oral contraceptive use cause the squamocolumnar junction to “roll out” or evert from its original position inside the external os to a position of enlarged cervical surface. Exposure of the columnar cells to low pH vaginal secretions, irritants, and a chang- ing hormonal environment lead to a gradual transforma- tion from columnar to squamous epithelium—a process called metaplasia (see Chapter 2). The area of dynamic change where metaplasia takes place is called the trans- formation zone . 6,7 The transformation zone is a critical area for the development of cervical cancer. Cervicitis Cervicitis is an acute or chronic inflammation of the cervix. Acute cervicitis may result from the direct infec- tion of the cervix or it may occur secondary to a vaginal or uterine infection. It may be caused by a variety of infective agents, particularly endogenous vaginal aer- obes and anaerobes, Streptococcus , Staphlococcus , and Enterococcus . 7 Other specific organisms include C. albi- cans and herpes simplex virus. Some agents are sexually transmitted, whereas others may be introduced by for- eign objects such as tampons or pessaries. 7 With acute cervicitis, the cervix becomes reddened and edematous. Irritation from the infection results in copious mucopurulent drainage. Depending on the causative agent, acute cervicitis is treated with appropri- ate antibiotic therapy. 7 Chronic cervicitis represents a low-grade inflamma­ tory process. It is seen most commonly in parous women and may be sequelae to minute lacerations that occur during childbirth, instrumentation, or other trauma. The organisms usually are nonspecific—often staphylo- coccal, streptococcal, or coliform bacilli. The symptoms of chronic cervicitis are well defined. The cervix may be ulcerated or normal in appearance; it may contain nabothian cysts; the cervical os may be distorted by old lacerations or everted to expose areas of columnar epi- thelium; and a mucopurulent drainage may be present. Untreated cervicitis may extend to include the devel- opment of pelvic cellulitis, low back pain, dyspareunia, cervical stenosis, dysmenorrhea, and ascending infection of the uterus or fallopian tubes. Diagnosis of chronic cervicitis is based on vaginal examination, colposcopy, Pap smear cytology, and occasionally biopsy to exclude malignant changes. Treatment usually involves cryosur- gery or cauterization, which causes the tissues to slough and leads to eradication of the infection. Cervical cancer is one of the best-understood cancers and potentially one of the most preventable. In the 1950s cervical cancer was the leading cause of cancer deaths in women in the United States, but the death rate has declined steadily over the past several decades due to prevention and early detection by cancer screening. 6 Worldwide, however, cervical cancer remains the second most common cancer in women. 7 Premalignant Lesions and Cancer of the Cervix

Pathogenesis and Risk Factors. The pathogenesis of cervical cancer has been linked to HPV infection by a series of epidemiologic, pathologic, and molecu- lar genetic studies. Of the approximate 100 types of HPV, about 40 affect the anogenital tract. About 15 of these types are associated with cancer and are known as high-risk groups, with subtypes 16 and 18 being the most important in terms of cervical cancer pathology (see Chapter 41). 6 HPV 16 accounts for almost 60% of cervical cancer cases, and HPV 18 for another 10%. 7 By contrast, low-risk types 6 and 11 are associated with genital warts (condylomata acuminata). Most cervical cancers begin their development in the squamous columnar cells of the transformation zone. The metaplastic cells within this zone represent the newest and least mature cells in the cervix. HPV infects immature basal cells of the squamous epithelium, but not mature superficial cells that cover the exocervix, vagina, or vulva, explaining the vulnerability of cells in the transformation zone to malignant transforma- tion. Even though HPV has been firmly established as a causative factor in cervical cancer, the evidence does not implicate HPV as the only risk factor. Most HPV infec- tions are transient, indicating the host’s defense system is able to eradicate the virus before it can cause neo- plastic changes in cervical cells. Other factors such as cigarette smoking, dietary and nutritional factors, early age of first sexual intercourse, family history of cervical cancer, immunodeficiency (e.g., HIV infection), multi- parity, and hormonal and other factors may play a role in determining whether a woman with HPV infection develops cervical cancer. 6,18 Two types of HPV vaccines are currently avail- able to prevent HPV infection: a quadrivalent vaccine (Gardasil) to prevent infection by HPV subtypes 16, 18, 6, and 11, 19 and a bivalent vaccine (Cervarix) to prevent infection by subtypes 16 and 18. 20 The quadrivalent vac- cine has been approved for females and males between the ages of 9 and 26 years, optimally before initiation of sexual activity. Human papillomavirus subtypes 6 and 11 cause the majority of venereal warts, while types 16 and 18 are responsible for over 80% of all cervical cancers. Because the bivalent vaccine does not protect again HPV subtypes 6 and 11, which are responsible for the majority of condyloma acuminiata (genital warts), it is approved for females between the ages of 9 and 26 years, but not for males. Premalignant and Malignant Lesions. One of the most important advances in the early diagnosis and treatment of cancer of the cervix was made possible by the observation that this cancer arises from pre- cancerous lesions that begin with the development of atypical cervical cells. There are variations in cell size and shape and changes in the nuclear and cytoplasmic parts of the cell, commonly referred to as dysplasia (see Chapter 7). These precancerous changes represent a continuum of morphologic changes with indistinct boundaries that may gradually progress to cancer in situ and then to invasive cancer, or they may spontane- ously regress.