Female Genital Tract- Cervix Flashcards
The ______________is both a sentinel for potentially serious upper genital tract infections and a target for
viruses and other carcinogens, which may lead to invasive carcinoma.
CERVIX
Worldwide, cervical
carcinoma is the_________________r in women, with an estimated 493,000 new cases
each year, over half of which are fatal. In the United States, 11,150 women were diagnosed with
cervical cancer and 3670 women died from this disease in 2007.
second most common cance
The potential threat of cancer
is central to ______________ and histologic interpretation of
________________specimens by the pathologist.
Papanicolaou (Pap) smear screening programs
biopsy
Inflammations
ACUTE AND CHRONIC CERVICITIS
At the onset of menarche, the production of estrogens by the ovary stimulates maturation of the
cervical and vaginal squamous mucosa and formation of intracellular glycogen vacuoles in the
squamous cells.
As these cells are shed, the glycogen provides a substrate for endogenous
vaginal aerobes and anaerobes, including streptococci, enterococci, Escherichia coli, and
staphylococci; however, the normal vaginal and cervical flora is largely dominated by
__________________
Lactobacilli produce lactic acid that maintains the vaginal pH below 4.5, suppressing
the growth of other saprophytic and pathogenic organisms. In addition, at low pH, lactobacilli
produce bacteriotoxic hydrogen peroxide (H2O2). [21] At higher, more alkaline pH caused by
bleeding, sexual intercourse, vaginal douching as well as during antibiotic treatment, lactobacilli
decrease H2O2 production, permitting the overgrowth of other microorganisms, which may
result in clinically apparent cervicitis or vaginitis. Some degree of cervical inflammation may be
found in virtually all women,and it is usually oflittle clinical consequence.However,infections by
gonococci, chlamydiae, mycoplasmas, and herpes simplex virus may produce significant acute
or chronic cervicitisand are important to identify due to their association with upper genital tract
disease, complications during pregnancy, and sexual transmission.
Marked cervical
inflammation produces reparative and reactive changes of the epithelium and shedding of
atypical-appearing squamous cells,and therefore may cause a nonspecific,abnormal Pap test
result.
lactobacilli
_______________ are benign exophytic growths that occur in 2% to 5% of adult women.
Endocervical polyps
Perhaps the major significance of polyps lies in their production of______________ that arouses suspicion of some more ominous lesion.
irregular vaginal “spotting” or
bleeding
Most polyps arise within the
_______________ and vary from small and sessile to large, 5-cm masses that may protrude
through the cervical os.
endocervical canal
All polyps are __________________________________often
accompanied by inflammation ( Fig. 22-14 ). Simple curettage or surgical excision effects a
cure.
soft, almost mucoid, lesions composed of a loose
fibromyxomatous stroma harboring dilated, mucus-secreting endocervical glands,
Endocervical polyp composed of ________________________
a dense fibrous stroma covered with
endocervical columnar epithelium.
Premalignant and Malignant
The pathogenesis of cervical carcinoma has been delineated by a series of epidemiologic,
clinicopathologic, and molecular genetic studies.
Epidemiologic data have long implicated a
sexually transmitted agent, which is now established to be _________.
HPV.
Note : For his discovery of HPV as a
cause of cervical cancer, Harald zur Hausen was awarded the Nobel Prize in 2008. HPVs are
HPVs are DNA viruses that are typed based on their DNA sequence and subgrouped into ______________ and __________
- high and
- low
oncogenic risk.
___________ are currently considered to be the single most
important factorincervical oncogenesis.
High oncogenic risk HPVs
High oncogenic risk HPVs have also been detected in
________________________________as detailed in Chapter 7 .
vaginal squamous cell carcinomas and in a subset of vulvar, penile, anal, tonsillar, and other
oropharyngeal carcinomas,
As noted earlier,__________________
are the cause of the sexually transmitted vulvar, perineal, and perianal condyloma acuminatum.
low oncogenic risk HPVs
There are 15 high oncogenic risk HPVs that are currently identified. From the point of view of
cervical pathology,_________________ are the most important.
HPV 16 and HPV 18
___________________alone accounts for
almost 60% of cervical cancer cases, and _____________ accounts for another 10% of cases;
other
HPV types contribute to less than 5% of cases, individually.
HPV 16
HPV 18
[22] The risk factors for cervical
cancer are related to both host and viral characteristics such as HPV exposure, viral
oncogenicity, inefficiency of immune response, and presence of co-carcinogens. [23] These
include:
- Multiple sexual partners
- A male partner with multiple previous or current sexual partners
* *3. Young age at first intercourse**
* *4. High parity** - Persistent infection with a high oncogenic risk HPV, e.g., HPV 16 or HPV18
- Immunosuppression
- Certain HLA subtypes
* *8. Use of oral contraceptives** - Use of nicotine
Genital HPV infections are extremely common; most of them are asymptomatic, do not cause
any tissue changes, and therefore are not detected on Pap test. Figure 22-15 shows agedependent
prevalence of HPVs in cervical smears in women with normal Pap test results.
The
high peak of HPV prevalence in 20-year-olds is related to sexual début, while the subsequent
decrease in prevalence reflects acquisition of immunity and monogamous relationships.
Most
HPV infections are transient and are eliminated by the immune response in the course of months. On average, 50% of HPV infections are cleared within 8 months, and 90% of infections
are cleared within 2 years. The duration of the infection is related to HPV type; on average,
infections with high oncogenic risk HPVs last longer than infections with low oncogenic risk
HPVs, 13 months versus 8 months, respectively. [24] Persistent infection increases the risk of
the development of cervical precancer and subsequent carcinoma.
HPVs infect ___________________ in areas of epithelial breaks, or
_______________ ( Fig. 22-16 ).
HPVs cannot infect the mature superficial squamous cells that cover the ectocervix, vagina, or
vulva.
Establishing HPV infection in these sites requires damage to the surface epithelium,
which gives the virus access to the immature cells in the basal layer of the epithelium.
immature basal cells of the squamous epithelium
immature metaplastic squamous cells present at the squamocolumnar junction
The
cervix, with its relatively large areas of immature squamous metaplastic epithelium, is
particularly vulnerable to HPV infection as compared, for example, with vulvar skin and mucosa
that are covered by mature squamous cells.
This difference in epithelial susceptibility to HPV
infection accounts for the marked difference in incidence of HPV-related cancers arising in
different sites, and explains the high frequency of cervical cancer in women or anal cancer in
homosexual men and a relatively low frequency of vulvar and penile cancer.
thats why! :)
Although the virus can infect only the immature squamous cells, replication of HPV occurs in the
maturing squamous cells and results in a cytopathic effect,_________________,” consisting of
nuclear atypia and a cytoplasmic perinuclear halo.
To replicate, HPV has to induce DNA
synthesis in the host cells. Since HPV replicates in maturing, nonproliferating squamous cells, it
must reactivate the mitotic cycle in such cells.
Experimental studies have shown that HPV
activates the cell cycle by interfering with the function of Rb and p53, two important tumor
suppressor genes
“koilocytic atypia
_______________ proteins are critical for the oncogenic effects of HPV.
They can promote cell
cycle by binding to RBandup-regulation of cyclin E (E7); interrupt cell death pathways by
binding to p53 (E6); induce centrosome duplication and genomic instability (E6, E7); and
prevent replicative senescence by up-regulation of telomerase (E6) ( Chapter 7 ).
Viral E6 and E7
________________
induces rapid degradation of p53 via ubiquitin-dependent proteolysis, reducing p53 levels by
two- to three-fold.
E7 complexes with the hypophosphorylated (active) form of RB, promoting its
proteolysis via the proteosome pathway. Because hypophosphorylated RB normally inhibits Sphase
entry via binding to the E2F transcription factor, the two viral oncogenes cooperate to
promote DNA synthesis while interrupting p53-mediated growth arrest and apoptosis of
genetically altered cells. Thus, the viral oncogenes are critical in extending the life span of
epithelial cells—a necessary component of tumor development.
HPV E6
The physical state of the virus differs in different lesions, being integrated into the host DNA in
cancers, and present as free (episomal) viral DNA in condylomata and most precancerous
lesions.
Certain chromosome abnormalities, including deletions at 3p and amplifications of 3q,
have been associated with cancers containing specific (HPV-16) papillomaviruses.
Even though HPV has been firmly established as a causative factor for cancer of the cervix, the
evidence does not implicate HPV as the only factor. A high percentage of young women are
infected with one or more HPV types during their reproductive years, and only a few develop
cancer.
Other cocarcinogens, the immune status of the individual, and hormonal and other
factors influence whether the HPV infection will regress or persist and eventually progress to
cancer. [23]
In addition to infecting squamous cells, HPVs may also infect _____________present in the cervical mucosa and cause malignant transformation, resulting in
adenocarcinomas, and adenosquamous and neuroendocrine carcinomas; these tumor
subtypes, however, are less common since glandular and neuroendocrine cells do not support
effective HPV replication.
glandular cells or neuroendocrine
cells
The classification of cervical precancerous lesions has evolved over time and the terms from
the different classification systems are currently used interchangeably.
CERVICAL INTRAEPITHELIAL NEOPLASIA
Note :
Hence a brief review of
the terminology is warranted. The oldest classification system classified lesions as having** mild
dysplasia** on one end and severe dysplasia/carcinoma in situ on the other.
This was followed by
cervical intraepithelial neoplasia (CIN) classification, with mild dysplasia termed CIN I,** moderate
dysplasia CIN II,** and severe dysplasia termed CIN III. Because the decision with regard to
patient management is two-tiered (observation versus surgical treatment), the three-tier
classification system has been recently simplified to a two-tiered system, with** CIN I renamed
low-grade squamous intraepithelial lesion (LSIL)** and** CIN II and CIN III** combined into one
category referred to as high-grade squamous intraepithelial lesion (HSIL)
CIN I renamed
_________________
low-grade squamous intraepithelial lesion (LSIL)
