58 D. Keith Edmonds1,2 1 Imperial College London, London, UK 2 Queen Charlotte’s and Chelsea Hospital, London, UK The vagina is the lowest part of the female internal genital tract. Clinical examination of the vagina is often limited as it is obscured during the use of a speculum and digital examination does not allow assessment. It is therefore only examined in detail in circumstances where there are specific symptoms to prompt vaginal examination. The vagina consists of a non‐keratinized squamous epithelial lining supported by connective tissue and surrounded by circular and longitudinal muscle coats. The muscle is attached superiorly to the fibres of the uterine cervix, and inferiorly and laterally to the pubococcygeus, bulbospongiosus and perineum. The lower end of the epithelium joins, near the hymen, the mucosal components of the vestibule and superiorly extends over the uterine cervix to the squamocolumnar junction. The vaginal epithelium has a longitudinal column in the anterior and posterior wall, and from each column there are numerous transverse ridges or rugae extending laterally on each side. The squamous epithelium during the reproductive years is thick and rich in glycogen. It does not change significantly during the menstrual cycle, although there is a small increase in glycogen content in the luteal phase and a reduction immediately premenstrually. The prepubertal and postmenopausal epithelium is thin or atrophic. The vagina has a varied bacterial flora in oestrogenized women, and knowledge of what is normal and abnormal is important for determining infection. The main organisms are listed in Table 58.1. Table 58.1 Normal frequency. Between puberty and the menopause the vaginal lactobacilli maintain a pH between 3.8 and 4.2 which protects against infection. Before puberty and after the menopause, the higher pH level and urinary and faecal contamination increase the risks of infection. Vaginal atrophy may also occur in the postpartum period with the hypo‐oestrogenic state during lactation. Normal physiological vaginal discharge consists of a transudate from the vaginal wall, squames containing glycogen, polymorphs, lactobacilli, cervical mucus and residual menstrual fluid, as well as a contribution from the greater and lesser vestibular glands. Vaginal discharge varies according to oestrogen levels during the menstrual cycle and is a normal physiological occurrence. Vaginal discharge does not normally have an unpleasant odour, and if this occurs in the presence of change in colour or copiousness, then it may indicate infection. Non‐specific vaginitis may be associated with sexual trauma, allergy to deodorants or contraceptives, and chemical irritation from topical antimicrobial treatment. Non‐specific infection may be further provoked by the presence of foreign bodies, for example ring pessary, continual use of tampons and the presence of an intrauterine contraceptive device. Bacterial vaginosis has been previously associated with the organism Gardnerella vaginalis but a wide range of organisms, including Mobiluncus spp., Bacteroides spp. and Peptostreptococcus, are also implicated. Some 50% of infected women are asymptomatic and the vagina is not usually inflamed, and therefore the term ‘vaginosis’ is used rather than vaginitis [1]. Examination will reveal a thin grey–white discharge and a vaginal pH increased to greater than 5. A Gram stain of collected material will show ‘clue’ cells, which consist of vaginal epithelial cells covered with microorganisms and the absence of lactobacilli. The diagnosis can also be confirmed by adding a drop of vaginal discharge to saline on a glass slide and adding one drop of 10% potassium hydroxide. This releases a characteristic fishy amine smell. Bacterial vaginosis may be associated with increased risk of preterm labour [2], pelvic inflammatory disease and postoperative pelvic infection [3,4]. The treatment of bacterial vaginosis is with metronidazole, either as 200 mg three times a day for 7 days or as a single 2‐g dose. Alternatively, clindamycin can be used as a vaginal cream. Trichomoniasis is a sexually transmitted disease caused by the parasite Trichomonas vaginalis. Symptoms usually appear 5–28 days after exposure and include a yellow–green vaginal discharge, often foamy, with a strong odour, dyspareunia and vaginal irritation. Of women infected, 10% also manifest a ‘strawberry’ cervix on examination (Fig. 58.1). Trichomonas vaginalis is a flagellated organism that can damage the vaginal epithelium, increasing a woman’s susceptibility to infection by human immunodeficiency virus (HIV). This is caused by lysis of the epithelial cells. Treatment is with metronidazole 400 mg three times daily for 7 days or tinidazole 2 mg as a single dose. As this is a sexually transmitted disease, diagnosis should prompt the gynaecologist to refer the patient to a genitourinary medicine clinic for contact tracing. This is a fungal infection commonly referred to as ‘thrush’. It is caused by any of the species of Candida, of which Candida albicans is the most common. This is an infection that causes vaginal irritation and vaginitis, which leads to itching, burning, soreness and a classic whitish or whitish‐grey cottage cheese‐like discharge. The irritation and inflammation spreads across the vulva and may also involve the perianal skin. Candida can be transmitted to a sexual partner, in whom it can cause red patchy sores near the head of the penis or on the foreskin, causing a severe itching and burning sensation. Candida albicans usually causes infection when production of lactic acid by lactobacilli is disturbed, resulting in a change in the pH in the vagina and subsequent overgrowth of Candida. Diabetics and patients using antibiotics for other infections have an increased incidence of candidiasis. This, in conjunction with other treatments (e.g. steroids) or conditions including HIV, leads to a weakening in the immune response, allowing Candida to thrive. Candida is frequently found in the vagina but it may also be part of the intestinal flora. The diagnosis is usually made on inspection, but a swab from the infected area will confirm the diagnosis in culture. Treatment for vaginal candidiasis is primarily with antifungal pessaries or cream inserted high into the vagina. Single‐dose preparations offer the advantage of compliance, and imidazole drugs (clotrimazole, econazole and miconazole) are effective in short courses of 1–14 days according to the preparation. Oral medication is also available in the form of fluconazole or itraconazole and these treatments are usually extremely effective at eradicating the disease. Some 10% of women who contract candidiasis will develop recurrent disease – this is particularly likely if there are predisposing factors, such as pregnancy, diabetes or oral contraceptive use. It is important to consider partner treatment in those patients who suffer recurrent disease and in those patients who are resistant to two courses of imidazoles. If bacteriological confirmation of recurrent disease is made, a number of long‐term treatments can be prescribed. These include fluconazole 100 mg orally every week for 6 months, clotrimazole 500‐mg pessary weekly for 6 months or itraconazole 400 mg every month for 6 months. There is extensive alternative medicine literature on the treatment of Candida but there is very little scientific evidence to prove its efficacy. Syphilis is uncommon among women in the UK. However, unusual vaginal lesions must raise suspicion, particularly if the patient or partner has recently travelled overseas. The primary lesion may be in the vagina or on the vulva or cervix. There is usually a single, painless, well‐demarcated ulcer with indurated edges, associated with lymphadenopathy. Secondary lesions include condylomata lata, mucous patches and snail‐track ulcers. Diagnosis is based on identification of the causative organism, Treponema pallidum, on dark‐ground microscopy, or by serological examination for syphilis, for example using enzyme‐linked immunosorbent assay (ELISA). For further details and specifics of treatment with Bicillin (i.e. procaine penicillin with benzylpenicillin sodium), see Chapter 64. Gonorrhoea may infect the cervix or Bartholin’s gland but not the vaginal epithelium, except in prepubertal girls or postmenopausal women. If there is suspicion of sexual abuse in a young child with a vaginal discharge, a swab for culture for Neisseria gonorrhoeae (see Chapter 64) should be taken. These paired glands close to the introitus are responsible for mucus secretion that keep the vagina moist and lubricated during sexual arousal. If the duct becomes blocked, mucus is unable to escape and therefore a cyst will form. If this becomes infected, abscess formation occurs and this can be extremely painful. The most common organisms causing this are Staphylococcus and Escherichia coli, although other organisms may be encountered including Neisseria gonorrhoeae or Chlamydia. Bartholin’s cysts or abscesses occur in about 3% of women, most commonly between the age of 20 and 30 years. Bartholin’s cysts may require no treatment unless troublesome, but abscesses almost always do. These may spontaneously rupture and resolve but recurrence rates are high. There are a number of surgical options, including incision and treatment with silver nitrate, marsupialization (which involves wide excision, drainage and eversion of the cyst mucosa to the vaginal skin), fistulization (incision, drainage and insertion of a catheter for 2–4 weeks), carbon dioxide laser incision and drainage, and needle aspiration of cysts. A meta‐analysis in 2009 failed to identify a best treatment approach [5]. Recurrence rates vary but are around 5%. Lesions due to human papillomavirus (HPV) and herpes simplex virus can be seen in the vagina. Further information is given in Chapter 64. This is seen not only following the menopause, but also prior to puberty and during lactation. Examination shows loss of rugal folds and prominent subepithelial vessels, sometimes with adjacent ecchymoses. The patient may present with vaginal bleeding, vaginal discharge or vaginal dryness and dyspareunia but also with urinary symptoms including frequency, nocturia, dysuria and recurrent urinary infection. Superficial infection, with Gram‐positive cocci or Gram‐negative bacilli, may be associated. Vaginal atrophy is symptomatic in 45% of postmenopausal women. Treatment requires oestrogen to restore the vaginal epithelium and pH level. This is usually by topical oestrogen cream, and some of the oestrogen will be absorbed systemically. The endometrial safety of long‐term use is uncertain. Preparations vary in length of recommended treatment, but this is usually for 3 months and then the effect is assessed. Repeated applications over time may be needed depending on symptoms returning. Alternatively, in postmenopausal women hormone replacement therapy can be used. This may follow coitus, with damage to the epithelium or less frequently the vaginal muscle wall, or the breakdown of adhesions at the vault following vaginal surgery (Fig. 58.2). It may be associated with parturition or be iatrogenic, for example ulceration associated with the use of a ring pessary. Trauma may be associated with significant haemorrhage and occasionally will leave vesical or rectal fistulae. A fistula may result from trauma, as described in the previous section, or it may be due to carcinoma or Crohn’s disease. Fistula of the anterior wall is now uncommon in association with childbirth, but rectovaginal fistula may follow an obstetric tear or extension of an episiotomy, and an incomplete or inadequate repair. Fistulae involving ureter, bladder or rectum may follow gynaecological surgery. Occasionally, deposits of endometriosis can be found beneath the vaginal epithelium in patients with rectovaginal endometriosis or following surgery or episiotomy. They may cause abnormal vaginal bleeding or pain. They are most easily identified while bleeding but have a blueish appearance at other times. Treatment can be by laser vaporization or excision, or by drug therapy as for endometriosis elsewhere. Vaginal intraepithelial neoplasia (VAIN) is seen in about 10% of patients with cervical intraepithelial neoplasia (CIN) (Fig. 58.3). It is almost always in the upper vagina and confluent with the cervical lesion [6]. It is uncommon to find VAIN in the presence of a normal cervix, but Lenehan et al. [7] reported that 43% of their patients with VAIN after hysterectomy had a history of negative cervical smears and benign cervical pathology. VAIN may be present in the vaginal vault or suture line after hysterectomy (Fig. 58.4) (this may be residual after CIN has been treated) or may be distant from the vault and associated with multicentric intraepithelial neoplasia. Hummer et al. [8] reported a series of 66 patients with VAIN and showed that one‐third of cases had developed within 2 years of treatment of the previous cervical lesion. The longest time interval between the diagnosis of CIN and VAIN was 17 years; the age of patients with VAIN in that series ranged from 24 to 74 years, with a mean age of 52 years. The aetiology of VAIN is similar to that of CIN, with HPV found in 98% of cases and HPV‐16 being found in 68% [9]. Extension of the transformation zone into the fornices would seem to be responsible, even though no abnormality was recognized when the cervical lesion was treated. A higher incidence of VAIN has been noted in patients on chemotherapy or immunosuppressive therapy. The role of radiotherapy for carcinoma of the cervix some 10–15 years prior to the development of VAIN has been noted, particularly when a subsequent lesion is in the lower vagina. It is thought by some [10] that a sublethal dose of radiation may induce tumour transformation and that VAIN or vaginal sarcoma may result. As for cervical lesions, VAIN I is equivalent to mild dysplasia, VAIN II to moderate dysplasia and VAIN III to severe dysplasia or carcinoma in situ. The disease is normally recognized as a result of abnormal cytology seen in a vaginal vault smear specimen. Townsend [11] recommended that vault smears should be performed annually for women after hysterectomy performed for CIN, and every 3 years if the hysterectomy was for benign disease. Current teaching discourages the need for any subsequent smears in this latter group but recommends follow‐up of patients who have had hysterectomy for cervical lesions. Gemmell et al. [12] recommend that vault smears should be taken 6 months, 12 months and 2 years after hysterectomy; the patient should then return to 5‐yearly screening. Colposcopic assessment of patients with abnormal vault smears will delineate areas of aceto‐white epithelium. Punctuation may be apparent in more than 50%, and areas of abnormality will often fail to stain following the application of Lugol’s iodine solution (Fig. 58.5). However, atrophic changes within the vagina may lead to extensive areas of non‐Lugol’s staining and difficulty in defining the limits of lesions. A preliminary 2‐week course of oestrogen cream to correct oestrogen deficiency and then colposcopic examination 2 weeks following this will improve the definition of lesions. Problems may be encountered in interpreting or gaining access to areas of change disappearing into post‐hysterectomy vaginal angles or suture line. Vaginal biopsies from the vault can usually be taken without anaesthesia, but occasionally difficult access into vaginal angles may require the use of general anaesthesia and appropriate vaginal retractors. No adequate study on the progression of VAIN to invasive disease has been reported. Among the series of patients reported by McIndoe et al. [13] were patients who had abnormal smears following hysterectomy; some of these patients were followed up for almost 20 years before developing invasive carcinoma while others progressed more rapidly. There has been a wide variety of treatments for VAIN. Surgical excision remains the mainstay of treatment, including excision biopsy for smaller lesions, partial vaginectomy for mutifocal disease and, rarely, total vaginectomy for extensive or persistent high‐grade VAIN. The difficult patient to treat is the one who has already undergone a hysterectomy for a cervical lesion and returns with an area of abnormality in the suture line. Whether leaving the vault open at the time of hysterectomy avoids sequestration of the vaginal mucosa above the usual suture line has not been proven. Ireland and Monaghan [14] found that 9 of 32 patients with VAIN had invasive carcinoma in the area of the suture line, and they emphasized both the difficulty in assessing the vaginal vault and the need for obtaining adequate tissue for histological examination. They therefore advocated partial vaginectomy whenever abnormal epithelium is seen at the angles or suture line of the vault. This procedure requires an abdominal approach after packing the vaginal vault and involves the mobilization of the ureters down to their insertion into the bladder, dissection of bladder and rectum from the vagina, and sufficient mobilization to allow removal of the upper 1–2 cm from the top of the vagina. The definition of just how much to remove is usually best achieved by commencing a mucosal dissection from below prior to packing the vagina. Occasionally, more extensive disease will require total vaginectomy followed by either skin grafting or mobilization of a loop of bowel to reconstruct the neovagina. There are some who advocate a vaginal approach [15], but access may not be easy and occasionally brisk bleeding from vaginal arteries may be encountered. Use of the carbon dioxide laser is more likely to be successful in treating those women who have not had hysterectomy and where the full extent of the lesion can be demarcated. It must be noted that the vaginal wall may be thin in postmenopausal women and the bladder and rectal mucosa less than 5 mm away. The advantage of the carbon dioxide laser over other forms of selective ablation, for example diathermy or loop excision, is that there should be greater control of the area and depth of laser vaporization. Techniques using high‐power density and rapid beam movement minimize carbonization and adjacent thermal necrosis to allow recognition of tissue architecture with removal of lesional epithelium down to the underlying stroma, thereby reducing the risk of bladder or bowel damage [16]. Medical treatment has also been used. Imiquimod 5% cream is commonly used and a recent review reported complete response rates in VAIN I–III of 57–86% [17]. Experience with the use of 5‐fluorouracil has been less extensive in the UK than in the USA. Caglar et al. [18] claimed that the subsequent denudation of epithelium was specific for only abnormal epithelium. However, sometimes epithelial ulceration is extensive, accompanied by severe vaginal burning, and subsequent healing may take several months. Treatment failure is common. A recent study by Rhodes et al. [19] examined the role of intravaginal oestrogen alone and in combination with other therapies. In the group treated with oestrogen alone, 90% had regression or cure; of those who had combined therapy, a cure rate of 81.3% was reported. In contrast, those treated without oestrogen had a cure rate of only 71%. The other option is to use radiotherapy by the intravaginal approach [20]. Such treatment may produce vaginal narrowing and interfere with coitus, and so this should be reserved for highly selected difficult cases and in older women in whom sexual activity has ceased. Local damage to the bladder and rectum are risks of brachytherapy.
Benign Diseases of the Vagina, Cervix and Ovary
Vagina
100%
50%
<5%
Staphylococccus epidermidis
+
−
−
Lactobacillus
+
−
−
Staphylococcus aureus
−
+
−
Staphylococcus mitis
−
+
−
Enterococcus faecalis
−
+
−
Streptococcus pneumoniae
−
−
+
Streptococcus pyogenes
−
−
+
Neisseria sp.
−
+
−
Neisseria meningitidis
−
+
−
Escherichia coli
−
+
−
Proteus sp.
−
+
−
Bacteroides sp.
−
−
+
Corynebacterium
−
+
−
Mycoplasma
−
+
−
Candida albicans
−
−
+
Vaginal infection
Bacterial vaginosis
Trichomoniasis
Vaginal candidiasis
Syphilitic lesions of the vagina
Gonococcal vaginitis
Bartholin’s gland diseases
Viral infections
Vaginal atrophy
Vaginal trauma
Fistula
Endometriosis
Vaginal intraepithelial neoplasia