Microbiology, inflammation, and Viral infections
Cytomorphologic features of human papillomavirus infection
Keratinized, mature squame
Keratinized, immature squame
Undifferentiated transformation zone
Loss of polygonal form, blunt or rounded corners
Thickened, wire loop appearance
Iso- and anisocytosis
Variable translucency and condensation
Bi- and multinucleation
be isodiametric in size, be moderately coarse, and appear iden-
tical; no parachromatin clearing and abnormal clumping are
observed (Fig. 7.58). At times the nuclear membrane may be
undulating and appear folded and wrinkled. Most affected cells
are intermediate squames. In the Bethesda System for reporting
gynecologic cytodiagnoses, CIN grades II and III are grouped
together as "high-grade" cervical intraepithelial lesions.103 *
grade II, or moderate dysplasia, has distinct nuclear chromatin
granularity, which is uniform and coarse and may be unevenly
distributed within the affected intermediate and parabasal-type
cells. Parachromatin clearing is inconspicuous (Fig. 7.59). This
is essentially a state of further exaggeration of the changes seen
in CIN grade I. Whereas all condylomas and three-quarters of
CIN grade I may reveal HPV antigen-positive cells, only two-
thirds of CIN grade II smears may manifest such findings. CIN
grade III, or severe or marked dysplasia, may be indistinguish-
able from carcinoma in situ. The biologic behavior and manage-
ment of these lesions are essentially identical.
The affected cells tend to appear mostly singly and are more
immature. They have distinct hyperchromasia with coarse but
uniform chromatin granularity, nuclear membrane undulation,
and uniformity. No nucleoli or parachromatin clearing is gener-
ally seen. At times, the affected cells may be in small groups and
fragments. Atypical, keratinized, and bizarre dyskeratotic forms
may appear in some cases.
Rarely (less than 5%), CIN grade III cells may be antigen-
positive. The integrated HPV genome, however, can be detected
within the infected cells by molecular hybridization techniques
Fig. 7.58 Human papillomavirus (HPV) infection,
intraepithelial neoplasm (LSIL, CIN I) changes. Vaginopancervical smear
(Papanicolaou x HP).
Fig. 7.59 Human papillomavirus (HPV) infection,
intraepithelial neoplasm (HSIL, CIN II/III) changes. Compared with Fig. 7.54,
the nuclear chromatin pattern is more irregular, coarser, and hyperchromatic.
Vaginopancervical smear (Papanicolaou x HP).
and PCR in greater than 90% cases. Given the high frequency of
oncogenic HPV DNA positivity in LSIL+ positive lesions, there
is little clinical utility for HPV HR testing in LSIL or HSIL cases.
Likewise, there is a limited role for HPV HR testing in ASC-H or
AGC cases. At present, there is no alternative marker to predict
which patients with these lesions are at greatest risk for progress-
ing to cancer. All patients with these significant cytologic abnor-
malities are recommended to undergo colposcopy and biopsy,
as outlined by the ASCCP management guidelines.107 *
exceptions in management apply to younger compliant patients
who are more likely to have a transient infection.
Using more sensitive techniques such as PCR, HPV genomes
have been detected in a large number of tumors, including
endocervical and ovarian adenocarcinomas; and vulvar, vaginal,
cervical, and anal carcinomas.110 The interrelationship of immuno-
logic, cellular, and mutagenic events and the role of other genital
infections such as HSV and CMV infections may all be important
in understanding the biology of this common genital infection.
It is not uncommon for HPV to manifest clinically in the con-
dition of altered immune response. Pregnancy and physical and
emotional stress may precipitate clinical HPV disease. Similarly,