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- Study Questions
HPV DNA, primarily types 16 and 18, has been shown to be present in more than 95% of cervical carcinoma specimens.
Because of their high occurrence in cervical cancers, these HPV types are considered to be high-risk, whereas HPV types 6 and 11 are considered low risk, and many other HPV types are considered benign. Yet, because many HPV-related infections (even those with types 16 and 18) are benign with lesions that can regress spontaneously, the utility of characterizing specific HPV types in clinical specimens remains to be determined.
Link with malignancies is well established, specifically with cancers involving the anogenital (cervical, vaginal, vulvar, penile, anal) tract and those involving the head and neck.1
HPV gains entry through breaks in the skin and replicates in the basal cell layer of the epithelium.
HPV has a tropism for squamous epithelium of skin and mucous membranes.
HPV DNA is replicated, and the viral particles are assembled in the nucleus of epithelial cells with late viral gene expression occurring in the upper layers of differentiated keratinocytes. In benign lesions, such as common skin warts, the viral DNA remains extrachromosomal in the nucleus of the infected epithelial cell. However, more commonly in carcinomas or high-grade intraepithelial lesions, viral DNA becomes integrated into the host genome. The viral genome encodes transforming genes, which have been shown to cause the inactivation of proteins that inhibit cellular growth, making infected cells more susceptible to mutation or other factors that may lead to the development of dysplasia and cancer.
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HPV types 16 and 18 are most commonly associated with cervical carcinomas.
Human papillomavirus (HPV) is the most common sexually transmitted infection.
It can be passed during anal, vaginal, or oral intercourse or by skin to skin contact during sexual activity.
There are many strains of HPV and the manifestation of the infection, if any, is related to the specific viral strain, the site of infection and host factors. Most infections with HPV are asymptomatic and cleared by the body’s immune system. HPV infections can lead to genital warts, cervical cancer in women, penile cancer in men, and anal or oropharyngeal cancers in both.
Treatment for HPV-related lesions includes immunologic agents, cryotherapy, acid application, and electrocautery.
Because of the ubiquity of the virus and the health risks related to exposure, vaccination against HPV is recommended routinely for both adolescent girls and boys.
HPV vaccination has been shown to reduce the incidence of genital warts and of cervical cancer.
1. HPV vaccine dosing for individuals younger than 15 years
For individuals younger than 15 years receiving human papillomavirus (HPV) vaccination, two vaccine doses administered at least six months apart are now recommended by the Centers for Disease Control and Prevention in the United States [1]. This new vaccine schedule is supported by data demonstrating that two vaccine doses in young females have similar immunogenicity to three doses.
2. Those 15 years and older should continue to receive a three-dose vaccine series.
Three doses are still recommended for individuals older than 15 years because they have lower immunologic responses to HPV vaccination.
Complications of Injecting Drug Use
- Local problems—Abscess (Figures 240-2
and 240-3; Abscess), cellulitis, septic thrombophlebitis, local induration, necrotizing fasciitis, gas gangrene, pyomyositis, mycotic aneurysm, compartmental syndromes, and foreign bodies (e.g., broken needle parts) in local areas.2A 32-year-old woman with type 1 diabetes developed large abscesses all over her body secondary to injection of cocaine and heroin. Her back shows the large scars remaining after the healing of these abscesses. (Courtesy of Richard P. Usatine, MD.)
- IDUs are at higher risk of getting methicillin-resistant Staphylococcus aureus(MRSA) skin infections that the patient may think are spider bites (Figure 240-4).
- Some IDUs give up trying to inject into their veins and put the cocaine directly into the skin. This causes local skin necrosis that produces round atrophic scars (Figure 240-5).
- IDUs are at risk for contracting systemic infections, including HIV and hepatitis B or hepatitis C.
- Injecting drug users are at risk of endocarditis, osteomyelitis (Figures 240-6and 240-7), and an abscess of the epidural region. These infections can lead to long hospitalizations for intravenous antibiotics. The endocarditis that occurs in IDUs involves the right-sided heart valves (see Chapter 50, Bacterial Endocarditis).2 They are also at risk of septic emboli to the lungs, group A β-hemolytic streptococcal septicemia, septic arthritis, and candidal and other fungal infections.
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A 42-year-old woman presents to the physician's office for a routine gynecologic examination. She is feeling well and has no specific complaints at this visit. While reviewing your records, you see that she has not come in for a Papanicolaou (Pap) smear in approximately 5 years. She admits that she has not come in because she has been feeling fine and did not think it was really necessary. She has a history of 3 pregnancies resulting in three full-term vaginal deliveries of healthy children. She was treated at 22 years of age for Chlamydia infection. She has never had an abnormal Pap smear. Her social history is notable for a 1-pack per day smoking history for the past 25 years. She is divorced from her first husband and is sexually active with a live-in boyfriend for the past 3 years. She has had 7 sexual partners in her lifetime. Her examination today is normal. You perform a Pap smear as part of the examination. The report arrives 10 days later with the diagnosis of high-grade squamous intraepithelial lesion.
Summary: A 42-year-old woman has high-grade squamous intraepithelial neoplasia on a Pap smear.
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Answer
A second-year medical student is researching the role of HPV in causing cancer. Which of the following types of cancer is HPV most commonly associated with?
A 40-year-old woman is diagnosed with cervical intraepithelial disease. Biopsy is suspicious for HPV related disease. What histologic features support the role of HPV?
Central, basophilic intranuclear cellular inclusions
Cowdry type A intranuclear cellular inclusions
Enlarged multinucleated cells
Cytoplasmic vacuolization and nuclear enlargement of cells
Numerous atypical lymphocytes
Answer
The correct answer is D.
D. HPV produces characteristic cytoplasmic vacuolization and nuclear enlargement of squamous epithelial cells, referred to as koilocytosis. Answers A, B, C, and E are incorrect. Both Cowdry type A intranuclear inclusions and enlarged multinucleated cells can be seen with HSV and varicella-zoster virus infections. Central, basophilic intranuclear inclusion bodies are seen in cytomegalovirus infections, whereas the presence of atypical lymphocytes is seen specifically in Epstein-Barr virus infections.
Which of the following viral families is known to be causally associated with tumor formation in healthy appearing human adults?
The correct answer is B. You answered D.
B. HPV is a member of the Papillomaviridae family and is causally associated with cervical cancer in otherwise healthy individuals. Answers A, C, D, and E are incorrect. Hepatitis C virus is a member of the flavivirus family and causes chronic hepatitis; in severe cases, it is a factor in the development of liver cancer. Paramyxoviruses include agents such as respiratory syncytial virus and measles virus; it is not associated with carcinomas. Human polyomaviruses include BK and JC viruses (named after the initials of the patients who from whom the virus was first isolated). These infections have been associated with immumocompromised patients, and their role in formation of human tumors is still under investigation.
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