II. DISEASE TRANSMISSION & AT-RISK POPULATIONS

HPV is a sexually transmitted disease.  HPV can be transmitted through sexual contacts including vaginal, anal, oral sex, or intimate skin-to-skin contact with someone who has the virus.  Newborn infants can be transmitted from infected mothers at birth.  About 90% of HPV infections are latent and eliminated by the body’s immune system in two years.  The incubation period of genital warts development is 2 weeks to 8 months, most commonly 2-3 month after HPV infection.  The latency period from the first HPV exposure to the development of cervical cancer is quite long and variable, and CDC offers no statistic data on this.  HPV is very infectious and the possibility of contracting HPV at a single sexual contact with an infected person is about 60%.  Because the immune system plays an important role to protect bodies from HPV infection, people with compromised or weak immune system have a higher risk of HPV infection progressing to cervical cancer.  At-risk people for HVP infections include smokers, HIV+ individuals, younger mothers, and mothers with many children. 

PREVALENCE

The prevalence of cancer-causing HPV infection in healthy women worldwide is reported to be 10%.  Rough statistics by continent indicate 22.9% in Africa, 20.5% in Central America/Mexico, 14.3% in South America, 13.8% in Northern America, 8.3% Asia, and 6.6% in Europe in 2007. Higher rates in Africa and Central America/Mexico most likely reflects the number of at-risk populations such as HIV+ individuals, mothers of many children, and young mothers.  Although HVP is not the single cause of the cervical cancer, the association between HVP infection and cervical cancer development is as high as 70%.  This prevalence interestingly corresponds with the mortality rates of cervical cancer in each region as shown GAVI's map below.

http://www.cdc.gov/globalhealth/immunization/sis/vacs_detail.htm

http://www.nature.com/nature/journal/v488/n7413_supp/full/488S2a.html

TRANSMISSION IN DETAILS (PATHOGENESIS)

Cancer-causing HPVs typically infect in the transformation zone of the cervix following a causative sexual contact.  HPVs gain an entry into the host cell  through a micro-abrasion or small tears sometimes occur in the lining of the cervical epithelium.  HPV viral particles opportunistically invade the cervical epithelium and infect down in the basal layer cells.  The HPV infection has a long clinically latency period, and papilloma virus replicate themselves with a faithful and robust mechanism in the dividing basal cells as episomal DNA. When dividing basal cells move up and begin to differentiate, viral genome activates amplification, which is followed by synthesis and assembly of the capsid proteins, and finally release of the virus in the upper layers of the epithelium. 

http://www.nature.com/nrc/journal/v7/n1/fig_tab/nrc2050_F1.html

In normally dividing cells, two proteins p53 and pRb (retinoblastoma) carefully regulate the cell replication process. P53 is responsible for DNA repair at cell cycle checkpoint and apoptosis.  pRb is responsible for preventing replication of damaged DNA in the cell.  Upon infection, HPVs express E6 and E7 genome and produce E6 and E7 proteins that interact with and block P53 and pRb respectively. These dis-regulated cells are instructed to divide and produce multiple copies of the HPV viral DNA. As a result of this unscheduled replication, abnormal cells are accumulated and the structural appearance of the epithelial tissue is disrupted. This results in the unscheduled cell replication. 

The extension of this disorganization of host cells throughout the upper layers and to the surface of the epithelium is clinically used to classify the degree of the lesion as follows:

▪️CIN1 (cervical intraepithelial neoplasia grade 1): Abnormal cell growth in the lower 1/3 of the basil epithelium (mild dysplasia)

▪️CIN2: Abnormal cell growth extends up to 2/3 of way from the basil epithelium (moderate to marked dysplasia)

▪️CIN3: Abnormal cell growth extends more than 2/3 from the basil epithelium.  This is the immediate precursor to cervical cancer (severe dysplasia to carcinoma in situ)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785934/

http://www.cdc.gov/vaccines/pubs/surv-manual/chpt05-hpv.html

http://www.nlm.nih.gov/medlineplus/ency/article/001491.htm

TREATMENT

At this moment, there is no cure for any types of HPV infection. In terms of warts-causing HPV, warts may go away without treatment as the immune system fights off the HPV infection.  The warts can be removed by freezing (cryotherapy) or by burning with an electric current (electrocautery) or by surgical removal.

High-risk cancer-causing HPV infection is most treatable when diagnosed early.  If Pap tests (==> see below "PREVENTION") show abnormal cells, treatments to remove these cells are available based on the woman's age, the abnormality of cells, and medical history. 

               

Laser therapy: use a narrow beam of intense light to destroy or remove abnormal cells

Cryotherapy: destroy by freezing abnormal tissue developed in a small area

LEEP (loop electrosurgical excision procedure): remove tissue by an electrical current that is passed through a thin wire loop 

         Conization: remove a cone-shaped piece of tissue using a knife, a laser, or the LEEP technique.

PREVENTION

As the rule of thumb for avoiding any STD infection, abstinence is the best way to prevent the HPV infection.  Also, other common safe practices apply for this virus infection, which include: using latex condoms, avoiding sexual contact with those having multiple sex partners.  There are vaccine called GARDASIL and CERVARIX available in the United States to prevent infections by two of the most common high-risk HPVs that cause genital cancer and two of the most common low-risk genital HPVs that cause genital warts.  For these vaccines to be effective, pre-teen girls/boys should receive three dozes of vaccine over a period of six months, before they initiate any sexual activities.   The vaccine works only for the type of HPVs included, but does not work to other types of HPVs.  Also, the vaccine does not treat already infected people.  Common side effects of HPV vaccines include pain, redness, or swelling in the arm at the shot was given, fever, headache, nausea, muscle or joint pain.  This vaccine is included as mandatory vaccines only in Virginia and Washington, DC, in the United States.  According to CDC, only 38% of girls aged 13-17 years had received the complete 3-dose vaccination in 2013, and the uptake rate among boys are much lower.

http://www.cdc.gov/std/stats13/other.htm

 Whether or not vaccinated in the past, women of ages 21-65 should take a Papnicolaou smear test (Pap-smear test) routinely to see if the cervix has abnormal or pre-cancerous cells.  The Pap-smear test procedure includes collecting the small amount of cells from the cervix, examining under microscope, and determining if cells are abnormal or cancerous.  In addition to the Pap-smear test, women aged 30-65 should take a separate HPV DNA test as the incident rate of cervical cancer is higher as the age goes up.  

            

http://www.cancer.gov/types/cervical/pap-hpv-testing-fact-sheet

MY COMMENTS

The HPV has years of latent period, and the infection does not immediately manifest any apparent signs or symptoms resulting devastating cancer developments, the pathological causal association is now clearly established.  Considering that cervical cancer is the second most prevalent cancer among women worldwide, affecting 11,000 women each year in the United States, and that 70% of cervical cancer is caused by the HPV infection, I think the cancer-causing HPV infection should be prevented as much as possible with any available means including vaccines and Pap tests for the better quality of life. Common side effects are reported, but no death is immediately associated with the vaccine shot.  However, from my personal point of view regarding mandatory vaccinations, HPVs should be prevented or treated at one’s discretions, rather than a part of the government-lead health care.  Because HPVs are different from other highly contagious diseases like chicken pox, measles, etc., in terms of clinical occurrence rates, and vaccinations cannot effectively establish herd immunity because HPVs infections are too prevalent.  Also, in the long years of clinical latency, people could die from other cause of death than HPV infections.  

At the same time, though, from epidemiologist’s point of view, I think the vaccine benefits outweigh the cost of getting cancer from the cost-benefit analysis, and could improve public health in general.  Especially, vaccines are effective for HPV-induced cancer in men, because it is hard to detect until signs become apparent.  In any way, the government should not stop encouraging people to receive HPV vaccines through financial supports and education so that all people are equally informed and have an access to the vaccines.