Figure 1. A representative parous adolescent cervix showing the outer boundaries of several important areas of exocervical epithelium that correspond to the histological representations in Figure 2. External os (os), new squamocolumnar junction (nscj), area of cervical ectopy (ect) between nscj and external os, cervical transformation zone (ctz) between the original squamocolumnar junction (oscj) and nscj that includes an area of immature metaplasia (im), which is lightened by the application of 5% acetic acid. Adapted from.^[15]

Figure 2. Schematic of the normal cervix, squamocolumnar junction and transformation zone. Also shown are effects of noninfectious inflammation and selected sexually transmitted infections that may enhance HIV shedding or susceptibility to HIV infection. Adapted from.^{[20, 21, 284]} (a). The exocervix (ex) (also termed the ectocervix or cervical portio) is completely covered with an extension of the vaginal stratified squamous epithelium [panel (i)]. The transition from the columnar epithelium of the endocervix (en) to the stratified squamous epithelium of the exocervix is abrupt and defines the original squamocolumnar junction (oscj). In approximately 25% of adolescent women, the squamocolumnar junction is at the external os(os).^[15] The stratified squamous epithelium reacts to estrogen by proliferating and maturing, with cornification of the superficial cells. (b). The endocervical canal, approximately 2.5 cm long, is lined by columnar epithelium that rests on a continuous, extremely thin basement membrane. Deeply penetrating invaginations of the mucin-secreting columnar epithelium form tubular-branching crypts [termed glands (tbg)], enhancing the secretory function of the endocervical epithelium. Unlike true glandular tissue, there is no distinction between the mucin-secreting columnar epithelial cells that line the cervical lumen or invaginated crypts. The columnar epithelium responds with maximal mucin production just before ovulation, when estrogen level is high and progesterone level is low. The stroma of the cervix is composed of collagenous connective tissue with small amounts of smooth muscle, elastic tissue and many CD8+ and CD4+ mononuclear lymphocytes and inflammatory cells. Hormone and other physical factors alter the shape and volume of the cervix, which results in eversion of the endocervical columnar epithelium onto the exocervix. Following menarche, in most adolescents and parous women, the endocervix protrudes to a variable extent onto the exocervical surface to form the endocervical columnar ectropion (ect).^[15] This process relocates the original squamocolumnar junction outside the external os. During gestation, there is an exaggerated protrusion of the endocervical ectropion onto the exocervix. Following delivery in the primigravida, the ectropion is rapidly replaced by immature squamous epithelium to form an immature cervical transformation zone that often persists for long periods (see Fig. 1).^[21] Whether this prolonged exposure of the squamocolumnar junction and columnar epithelium of the ectropion to the contents of the vaginal vault increases the risk of HIV infection post-partum is not known (panel (ii)), but ectopy is an associated risk factor for HIV infection.^[16,17] (c). A composite schematic of the exocervix in response to noninfectious and infectious provocation.^[284] Areas of ectropion are eventually replaced (metaplasia) by the in-growth of squamous epithelium under the columnar epithelium (termed epidermalization^[20] or epithelialization^[21]) and intrinsic squamous differentiation of subcolumnar reserve cells to define areas of immature metaplasia (im) (see also Fig. 1). Squamous epithelium eventually replaces the columnar epithelium of the ectropion to form the cervical transformation zone(ctz) along with a new squamocolumnar junction (nscj)^[21] (see also^[15]). During adulthood, the new squamocolumnar junction migrates toward the cervical os along the transformation zone and is usually concealed within the os by the time of menopause (panel (iii)). During this process, the squamous epithelium may overgrow the columnar papillae and obstruct the crypt openings to form mucous (Nabothian) cysts (nc), the mucin-distended cyst spaces are lined by low columnar endocervical cells. The formation of the cervical transformation zone may be associated with a strong noninfectious inflammatory response in the submucosum, epithelial erosions and shallow ulcerations (su), which characterize variable degrees of noninfectious cervicitis.^[284] Some patterns of inflammation are associated with certain pathogens that produce an infectious cervicitis involving either the squamous epithelium or the columnar epithelium.^[284] For example, herpesvirus infection is associated with deep, herpeticepithelial ulcers (huc) and a pronounced lymphocytic infiltrate (panel (iii)). Chlamydia trachomatis infects the columnar epithelial cells and is associated with submucosal lymphoid germinal centers (lgc), a prominent plasmacytic infiltrate and mucopurulent cervicitis with polymorphonuclear cells in the cervical lumen [panel (iv)]. Shallow epithelial erosions (er) arise from rupture of chlamydial inclusions (ci) and microabscesses (ma), exposing the basement membrane and underlying mononuclear inflammatory infiltrate to the contents of the endocervical canal lumen or vaginal vault (e.g., HIV-infected semen).

Figure 3. Sampling of the female genital tract for HIV. The sequence of sampling procedures is as follows. (1) Each Sno-strip^® wick absorbs approximately 8 µl of fluid up to the strip shoulder; three wicks are generally used per sampling procedure. (2) Cervicovaginal lavage with 10 ml of phosphate-buffered saline. (3) A cytobrush sample is collected and the cytobrush is placed into 500 µl of guanidinium buffer. A more detailed description of the sampling procedures is provided in.^[36]

Figure 4. Localization of HIV in semen, adapted from.^{[285, 286]} The morphological analysis data (cell numbers and percentages) represent an analysis of whole, unfractionated semen and were provided by Charles Muller, PhD (personal communication, 2002), and.^[285] The detection of HIV in the various semen fractions was adapted from.^[286]